Document Type: Review Article

Diabetes-Associated Dry Eye Syndrome: Clinical Features, Underlying Molecular Mechanisms and Treatment Options

Pages 1-6

https://doi.org/10.22034/thr.2024.212234

Amirsaleh Abdollahi, Mehran Frouzanian

Abstract The global diabetes epidemic continues to rise, with complications extending beyond diabetic retinopathy (DR) and cataracts to include dry eye syndrome (DES), or keratoconjunctivitis sicca. Approximately 54% of individuals with diabetes experience DES, yet the condition remains poorly understood. Diabetes mellitus (DM) disrupts tear film homeostasis through mechanisms such as lacrimal gland dysfunction, Meibomian gland dysfunction, and abnormal tear dynamics. Chronic hyperglycemia, diabetic neuropathy, systemic inflammation, and altered mucin secretion exacerbate these changes, leading to tear instability and ocular surface damage. Risk factors for DES include advanced age, female sex, smoking, and higher glycated hemoglobin (HbA1c) levels. Surgical interventions for diabetes-related ocular complications, such as cataract surgery, intravitreal injections, and pan-retinal photocoagulation, further increase the risk of DES. Treatment strategies for diabetic dry eye (DMDES) include artificial tears, anti-inflammatory drugs like corticosteroids, cyclosporin A, tacrolimus, and autologous blood serum. However, these treatments address symptoms rather than underlying causes, with potential side effects. Emerging therapies, including gene-based approaches, show promise but require further research. Given the high prevalence of DMDES and its potential impact on quality of life, routine ocular surface and tear function assessments are recommended in diabetic care. Early diagnosis, glycemic control, and personalized treatment regimens are critical for preventing complications. Future studies must focus on targeted therapies to better manage DMDES and improve patient outcomes.
 

Exploring the Synergistic Potential of Combined Acupuncture and Repetitive Transcranial Magnetic Stimulation for Postpartum Depression

https://doi.org/10.22034/thr.2025.236685

Zamdar H Rasul Karim

Abstract Background: Postpartum depression (PPD) is a prevalent and serious global mental health disorder. Conventional pharmacological treatments like SSRIs have limitations, including side effects and breastfeeding safety concerns, prompting the exploration of alternative therapies.
Objective: This narrative review synthesizes current evidence on the efficacy, mechanisms, and clinical implementation of combined acupuncture and repetitive transcranial magnetic stimulation (rTMS) for PPD.
Methods: A narrative review was conducted to analyze and integrate existing research on the integrative use of acupuncture (a Traditional Chinese Medicine practice) and rTMS (a non-invasive neuromodulation technique) for treating PPD.
Results: Evidence suggests that combined acupuncture-rTMS therapy may produce synergistic effects. Potential benefits include a greater reduction in depressive symptoms, improved neuroendocrine regulation, and enhanced overall quality of life compared to either intervention administered alone.
Conclusion: The combination of acupuncture and rTMS represents a promising integrative approach for PPD. Further research is needed to optimize treatment protocols, identify predictive biomarkers, and evaluate long-term outcomes.

The Role of Varicocelectomy in Enhancing Fertility Outcomes: A Review Article

Pages 1-6

https://doi.org/10.22034/thr.2024.212236

Ahmad Deylami, Mehran Frouzanian, Mehdi Younesi Rostami, Behkam Rezaiemehr, Amirsaleh Abdollahi, Mohadeseh Modanlu, Maryam Shahbazinia, AmirReza Ranjbar, Fatemeh Rajabian

Abstract Varicocele is the leading cause of male infertility and can often be corrected or improved through a range of surgical and radiological methods. Consequently, it appears logical that varicocele should be treated in infertile men who have this condition. Varicocele, an enlargement of the pampiniform plexus veins affecting 15–20% of men, is more common in those with infertility concerns. Its impact on spermatogenesis is linked to oxidative stress, hypoxia, and immune responses, which may be alleviated by varicocelectomy. Varicocelectomy has been associated with improvements in sexual function, hormonal profiles, and fertility, particularly in men with hypogonadism. This review evaluates its effects on testosterone levels, semen quality, and fertility outcomes, highlighting the advantages of microsurgical varicocelectomy, such as improved sperm quality, higher spontaneous pregnancy rates, and fewer complications. However, patient outcomes depend on surgical indications, pre-existing conditions, and individual expectations.  Emerging evidence suggests that repairing varicoceles before assisted reproductive technology (ART) can enhance fertility outcomes. Further studies are needed to refine treatment criteria and expand options for diverse patient groups, including adolescents and men with pain-related varicoceles. The review also emphasizes the need for standardized diagnostic and treatment protocols.

The Influence of Stereotactic Body Radiotherapy (SBRT) on Biomarker Profiles in Lung Cancer: A Detailed Overview

https://doi.org/10.22034/thr.2025.236663

Babak Olia, Karomat Sobirova, Masharipova Ravqat, Madrimov Javoxir Islombek o'g'li, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O'ktamovich, Ulliyeva Rayxon, Ataniyazov Aybek, Mahdi Hazratgholi

Abstract Background: Stereotactic Body Radiation Therapy (SBRT) represents the standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC) and is increasingly utilized for oligometastatic disease. Its distinct radiobiological profile, involving high doses per fraction, triggers complex tumor-killing effects and systemic biological reactions not fully detectable through conventional imaging.
Objective: This review aims to summarize and critically assess current evidence regarding dynamic alterations in circulating, tissue, and imaging biomarkers after SBRT for lung cancer, and to explore their clinical significance.
Methods: A narrative synthesis of scientific literature from PubMed, Scopus, and Google Scholar was conducted, focusing on studies published between 2005 and 2024. Key search terms included "SBRT," "SABR," "lung cancer," "biomarker," "ctDNA," "immunotherapy," "cytokines," and "radiation pneumonitis."
Results: SBRT prompts a rapid, biphasic shift in tumor-derived biomarkers such as circulating tumor DNA (ctDNA), characterized by an initial post-treatment surge followed by reduction in responders. It significantly influences the immune system, inducing immunogenic cell death, expanding tumor-specific T-cell populations, and increasing checkpoint molecule expression like PD-L1. Additionally, SBRT modifies levels of cytokines (e.g., IL-6, TGF-β) and angiogenic factors (e.g., VEGF), which correlate with both treatment effectiveness and side effects like radiation-induced lung injury. Certain genetic polymorphisms also appear promising for predicting toxicity risk.
Conclusion: SBRT induces a dynamic and multifaceted change in the biomarker profile of lung cancer patients. These biomarkers offer considerable potential for personalizing treatment, predicting outcomes, monitoring response, and rationally planning combination therapies, especially with immunotherapy. Future prospective and validated studies are necessary to integrate these findings into clinical practice.

Pain Management and Anesthesia Considerations in Thyroid Carcinoma: An Emphasis on Anaplastic, Papillary, Follicular, Hurthle Cell, and Medullary Subtypes

Pages 1-7

https://doi.org/10.22034/thr.2024.212239

Amin Ghanbarpour Juybari, Amirsaleh Abdollahi, Alireza Karimi Varaki, Ali Pahnabi, Mehran Frouzanian, Mohamad Javad Bay, Mohammad Modarresi

Abstract Thyroid carcinoma encompasses a heterogeneous group of malignancies, each with distinct biological behaviors, therapeutic strategies, and challenges in pain management and anesthesia. This review delves into the subtypes of thyroid carcinoma—anaplastic, papillary, follicular, Hurthle cell, and medullary—emphasizing the critical interplay between effective pain control and surgical outcomes. Anaplastic thyroid carcinoma (ATC), characterized by rapid progression and local invasion, necessitates multimodal pain management, including systemic analgesics and nerve blocks, to address severe discomfort caused by structural compression. Papillary and follicular thyroid carcinomas, generally indolent but prone to recurrence, require tailored anesthesia and postoperative pain protocols, incorporating techniques like cervical plexus blocks to reduce opioid reliance. Unique challenges are posed by Hurthle cell carcinoma (HCC) and medullary thyroid carcinoma (MTC). HCC, often associated with poor prognosis, demands precise surgical techniques to enhance survival, while MTC involves hereditary and sporadic forms with systemic manifestations complicating pain management. Advanced surgical methods, including transoral and robotic thyroidectomy, are explored for their efficacy in reducing complications and enhancing patient satisfaction. For patients with genetic predispositions, early prophylactic surgeries significantly mitigate risks. Anesthesia considerations are paramount, particularly in advanced ATC, where airway management is crucial. Techniques such as total intravenous anesthesia (TIVA) and regional nerve blocks optimize perioperative outcomes while minimizing systemic side effects. This narrative underscores the importance of interdisciplinary collaboration and individualized care in addressing the multifaceted needs of thyroid carcinoma patients, ultimately aiming to improve survival rates and quality of life.

The Role of Early Intravenous Immunoglobulin and Nursing Process Optimization in Modulating Inflammation and Improving Outcomes in Pediatric Severe Adenovirus Pneumonia: A Comprehensive Review

https://doi.org/10.22034/thr.2025.236668

Salayeva Navbahor, Docent. Sevara Sadullayeva, Ollaberganov Zayniddin Umarbekovich, Niginabonu Khajiqurbonova, Sultanov Muhammad, Saginova Aygerim Sisenbayevna

Abstract Background: Severe adenovirus pneumonia (SAP) in children is a critical illness characterized by a dysregulated hyperinflammatory response. The adjunctive role of early intravenous immunoglobulin (IVIG) and optimized nursing care in modulating this inflammation remains a key area of clinical investigation.
Objective: This review evaluated current evidence on the efficacy of early IVIG administration and nursing process optimization (NPO) in improving clinical and biochemical outcomes for pediatric SAP.
Methods: A comprehensive analysis of clinical studies, including a pivotal randomized controlled trial was conducted. The review focuses on IVIG's immunomodulatory mechanisms and the impact of structured nursing interventions on care delivery.
Results: Early IVIG administration is associated with significant reductions in key inflammatory markers (CRP, PCT, IL-8) and leads to superior clinical outcomes, including shorter hospital stays, fever duration, and mechanical ventilation requirements, alongside lower complication rates. Concurrently, implementing NPO protocols dramatically reduces infusion-related adverse events.
Conclusion: The synergistic application of early IVIG and NPO presents a promising, holistic strategy for managing pediatric SAP by effectively modulating inflammation and enhancing the safety of care delivery. This combined approach warrants broader clinical adoption and further long-term study

Unraveling the Spectrum of Thyroid Carcinoma: From Aggressive Anaplastic to Curable Differentiated Forms - A Comprehensive Narrative Review

Pages 1-9

https://doi.org/10.22034/thr.2025.213077

Rostam Poormousa, Mehran Frouzanian, Amirsaleh Abdollahi, Mohamad Javad Bay, Kasra Hasannejad, Reza Talaei

Abstract Thyroid carcinoma encompasses a spectrum of malignancies with distinct clinical characteristics, management strategies, and prognoses. This narrative review article provides an in-depth examination of anaplastic thyroid carcinoma (ATC), papillary thyroid carcinoma (PTC), Hurthle cell carcinoma (HCC), and medullary thyroid carcinoma (MTC), offering insights into their epidemiology, diagnostic and treatment modalities. Anaplastic thyroid carcinoma is a highly aggressive and undifferentiated form of thyroid cancer, often associated with poor prognosis. Treatment strategies include combined resection and radiotherapy, but late-stage cases exhibit limited therapeutic options, emphasizing the need for novel therapeutic approaches. Papillary thyroid carcinoma, the most common thyroid cancer, generally carries a favorable prognosis. The article discusses surgical interventions like total thyroidectomy and lobectomy, along with minimally invasive techniques such as transoral endoscopic thyroidectomy vestibular approach (TOETVA) and robotic thyroidectomy. The importance of considering health-related quality of life in the treatment decision-making process is highlighted. Hurthle cell carcinoma, a rare and aggressive subtype, is explored with a focus on factors influencing prognosis. Surgical management, including thyroid lobectomy, completion thyroidectomy, and iodine-131 therapy, is discussed in detail. Medullary thyroid carcinoma is categorized into hereditary and sporadic forms, each requiring specific approaches. The review emphasizes the significance of genetic testing for patients at risk of multiple endocrine neoplasia syndrome (MEN2) and the need for early thyroidectomy in genetic RET mutation carriers. Furthermore, the article evaluates the extent of surgery, the role of radioiodine therapy, and the significance of follow-up in treating differentiated thyroid carcinomas (DTC). Surgical approaches for follicular thyroid carcinoma (FTC) and factors influencing the decision for total thyroidectomy versus lobectomy are elaborated upon. In summary, this narrative review provides a comprehensive overview of thyroid carcinoma subtypes, their epidemiology, surgical interventions, and postoperative management, offering valuable insights for clinicians and researchers in the field.
 

The Combined Impact of Preoperative Nutritional Support and Esketamine on Postoperative Recovery, Immune Function, and Quality of Life in Older Patients Receiving Thoracoscopic Lung Cancer Surgery

https://doi.org/10.22034/thr.2025.236686

Ismael Bilal Ismael, Sarwar Nawzad Jafar

Abstract Background: Older patients undergoing thoracoscopic radical resection for lung cancer face considerable risks of postoperative pain, weakened immunity, and malnutrition, which can slow recovery. Multimodal approaches are needed to enhance results. This review explores the combined benefits of preoperative nutritional support and analgesia based on esketamine.
Methods: A narrative literature review was performed using databases including PubMed, Embase, and the Cochrane Library up to 2025. The search targeted clinical trials, randomized controlled trials (RCTs), and meta-analyses on esketamine, preoperative nutrition, and outcomes in thoracic or cancer surgery. Information was combined to assess impacts on pain relief, immune and nutritional indicators, and recovery measures.
Results: Research consistently shows that esketamine notably decreases postoperative pain scores and opioid use while reducing opioid-related side effects. Preoperative immunonutrition lessens the surgery-related drop in immune markers (IgG, IgM, IgA) and nutritional proteins (Alb, TRF, PAB). Together, these approaches work synergistically to speed gastrointestinal recovery, reduce hospital stay, and improve health-related quality of life scores in older surgical patients.
Conclusion: Incorporating preoperative nutritional support and esketamine into Enhanced Recovery After Surgery (ERAS) protocols offers a promising multimodal method to improve perioperative care. This approach effectively manages pain, supports immune and nutritional health, and encourages quicker recovery, supporting broader clinical use and additional large-scale RCTs.

Therapeutic Potential of Shugan Jieyu Capsule and Group Psychological Counseling for Alexithymia and Neuroimmune Dysfunction in Hemodialysis Patients

https://doi.org/10.22034/thr.2025.236659

Daniel S. Hamid

Abstract Background: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) experience a high psychological burden, with frequent occurrences of alexithymia, anxiety, and depression. These psychological issues are increasingly associated with disruptions in neuroimmune and neuroendocrine pathways. This review examines the basis and supporting data for using a combined approach of Shugan Jieyu Capsule (SJC) and group psychological counseling (GPC) to target both the psychological and biological aspects of this complex condition.
Methods: A synthesis of existing literature was conducted, focusing on the pathophysiology of alexithymia in HD patients, the pharmacological effects of SJC, the therapeutic mechanisms of GPC, and the role of biomarkers such as Orphanin FQ (OFQ), Interleukin-2 (IL-2), Corticotropin-Releasing Hormone (CRH), Neurogranin, and soluble Fractalkine (sCX3CL1).
Results: Recent evidence indicates that a combined strategy of SJC and GPC is more effective than standard care alone. This integrated approach has been found to significantly reduce symptoms of alexithymia, anxiety, and depression; enhance sleep quality, self-care capacity, and social functioning; and improve overall quality of life. Importantly, these psychological improvements are associated with changes in key biomarkers, including decreased serum levels of OFQ, IL-2, CRH, Neurogranin, and sCX3CL1, suggesting a positive effect on stress response, synaptic function, and neuroinflammation.
Conclusion: The combination of Shugan Jieyu Capsule and group psychological counseling represents a promising, multi-targeted strategy for managing the psychosomatic challenges in hemodialysis patients. This method not only improves clinical symptoms but also appears to address underlying neuroimmune and neuroendocrine imbalances, offering a holistic approach to enhancing patient outcomes in ESRD care.

Muscle Morphology and Its Role in Chronic Neck Pain: A Review Article

Pages 1-11

https://doi.org/10.22034/thr.2025.509466.1007

Mehran Frouzanian, Seyed Sadegh Shirdel, Hosein Meskar, Mostafa Shahrezaee, Mostafa Chamanara, Amin Ghanbarpour Juybari, Amirsaleh Abdollahi

Abstract Introduction: Chronic neck pain (CNP) is a common and debilitating condition that significantly impacts quality of life, productivity, and overall well-being. Muscle morphology, particularly in the deep cervical muscles, plays a critical role in the onset, development, and persistence of chronic neck pain. This review investigates the relationship between muscle changes, including atrophy, fat infiltration, and alterations in muscle fiber composition, and their contribution to cervical instability, pain, and functional limitations.

Methods: The review examines existing literature on muscle morphology in CNP, focusing on the role of deep cervical muscles in the pathophysiology of neck pain. It also highlights how factors such as disuse, changes in neural activation, and chronic inflammation exacerbate these muscle alterations. The role of advanced imaging techniques, such as MRI, in identifying these changes is also discussed.

Results: Alterations in muscle morphology, including atrophy and fat infiltration, contribute to weakness and reduced spinal stability, which are key factors in the development and persistence of chronic neck pain. Neural activation changes and chronic inflammation further exacerbate muscle degeneration. Advanced imaging techniques, particularly MRI, play a crucial role in assessing these morphological changes and enabling personalized treatment strategies.

Conclusion: Muscle degeneration, including atrophy and fat infiltration in the cervical spine, is a significant factor in chronic neck pain. Effective management requires a comprehensive approach, including rehabilitation programs focused on muscle strengthening, postural correction, and ergonomic adjustments. Fat infiltration in cervical muscles is a significant marker of structural and functional impairment in cervical spine disorders. Further research is needed to explore the mechanisms behind muscle changes in CNP and to develop more targeted and effective interventions.

The Effectiveness of Combined Zoledronic Acid, Calcium, and Calcitriol Treatment for Osteoporosis in the Elderly: A Detailed Review of Bone Density, Metabolic Indicators, and Clinical Results

https://doi.org/10.22034/thr.2025.236681

Mohammed Ibrahim Mohialdeen Gubari

Abstract Introduction: Managing osteoporosis in the elderly, a common issue in aging populations worldwide, demands effective approaches to lower fracture risk and maintain life quality. Although calcium and vitamin D provide basic support, strong anti-resorptive drugs such as zoledronic acid are frequently required. This review compiles evidence on using zoledronic acid together with calcium and calcitriol to treat primary osteoporosis in older adults.
Methods: A narrative literature review was performed. Searches were conducted in electronic databases like PubMed, Scopus, and Web of Science for pertinent clinical trials, meta-analyses, and review articles published through 2024. Important search terms were "zoledronic acid," "senile osteoporosis," "bone mineral density," "bone turnover markers," "calcitriol," and "quality of life." Emphasis was placed on studies involving older populations and combinations of these treatments.
Results: Strong evidence shows that triple therapy (zoledronic acid, calcium, and calcitriol) is more effective than dual therapy (calcium and calcitriol alone) in substantially raising bone mineral density (BMD) at the lumbar spine, femoral neck, and hip. It creates a better bone metabolic state, marked by a significant reduction in resorption markers (CTX-1) and a subtle adjustment of formation markers (PINP, Osteocalcin). This treatment also leads to greater enhancements in quality of life scores (QUALEFFO-41) and shows a tolerable safety profile, with short-lived acute-phase reactions being the most frequent side effects.
conclusion: The combination treatment provides a synergistic, multi-target strategy. Zoledronic acid strongly hinders osteoclast-driven bone resorption, while calcium and calcitriol maintain a positive calcium balance and directly affect bone cell activity. This leads to stronger bones, decreased fracture risk, and better patient well-being. Long-term adherence and uncommon side effects are still factors to consider, but the benefit-risk balance is very positive for high-risk elderly patients.

Comparing Different Treatment Options for Plantar Fasciitis, A Review Article

Pages 1-7

https://doi.org/10.22034/thr.2025.509508.1008

Mostafa Shahrezaee, Seyed Sadegh Shirdel, Mohsen Chamanara, Hosein Meskar, Abolfazl Firouzian, Majid Sadeghi, Amirsaleh Abdollahi

Abstract Introduction: Plantar fasciitis is a prevalent condition characterized by chronic heel pain, primarily caused by inflammation of the plantar fascia. The condition significantly impairs daily activities and quality of life, presenting a challenge for healthcare providers. Numerous treatment modalities, ranging from conservative measures to invasive interventions, have been explored to manage the symptoms and promote healing. However, the effectiveness of these treatments, especially when combined, requires further evaluation.

Methods: This review extracted data from existing studies comparing the effectiveness of corticosteroid injections (CSI) alone versus their combination with needling techniques (such as dry needling and percutaneous needle electrolysis) for chronic plantar fasciitis. The literature was assessed through systematic reviews, randomized controlled trials, and clinical studies that evaluated pain relief, functional recovery, and long-term outcomes. Studies on adjunctive treatments like extracorporeal shockwave therapy (ESWT) were also considered to provide a broader comparison.

Results: Corticosteroid injections provide significant short-term pain relief but are limited in their long-term efficacy, with potential complications like tissue atrophy. Dry needling and other needling therapies, when used in combination with CSI, have shown improved long-term outcomes in terms of pain reduction and functional recovery. ESWT consistently outperformed other treatments in long-term studies for both pain management and functional improvement. Combining treatments appears to yield enhanced results, although conclusive evidence on optimal treatment protocols remains insufficient.

Conclusion: Chronic plantar fasciitis requires a multi-faceted treatment approach. While corticosteroid injections remain a common short-term solution, combining them with needling techniques may offer superior long-term benefits. Extracorporeal shockwave therapy also shows promise for sustained relief. Further research is needed to establish optimal treatment protocols and to better understand the combined effects of these interventions. An individualized treatment strategy that addresses both symptoms and underlying causes is essential for improving patient outcomes.

The Impact of Serum 25-Hydroxyvitamin D and Genetic Factors on Liver Cancer Risk: An Updated Review and Mendelian Randomization Analysis

https://doi.org/10.22034/thr.2025.236687

Priya Priyadarshini

Abstract Background: Liver cancer, mainly hepatocellular carcinoma (HCC), presents a major global health challenge with high mortality. While established risk factors such as viral hepatitis and alcohol consumption are widely recognized, there is growing interest in modifiable factors like vitamin D (VD) deficiency. Observational studies indicate a link between low serum 25-hydroxyvitamin D (25(OH)D) and increased liver cancer risk, though confounding factors and reverse causality complicate causal conclusions.
Objectives: This review aims to integrate current findings on the relationship between serum 25(OH)D and liver cancer risk, critically assess causality using Mendelian randomization (MR) evidence, and explore mechanistic insights from genetic research.
Methods: A narrative literature review was conducted using PubMed and Google Scholar, focusing on epidemiological studies, MR analyses, and mechanistic research published up to 2025. Search terms included "25-hydroxyvitamin D," "liver cancer," "hepatocellular carcinoma," "Mendelian randomization," and "genetic polymorphisms."
Results: Case-control and cohort studies consistently show that liver cancer patients have significantly lower serum 25(OH)D levels compared to healthy individuals. MR studies, using genetic variants in DHCR7CYP2R1, and VDR genes as instrumental variables, strongly indicate a causal protective effect of higher 25(OH)D concentrations on liver cancer risk. For example, alleles associated with increased 25(OH)D, such as those in DHCR7 (rs12785878) and VDR (rs2228570), correlate with a 20-30% reduction in liver cancer odds. These findings are supported by biological mechanisms, including VD's anti-proliferative, pro-apoptotic, and anti-inflammatory actions mediated through the VDR receptor in liver cells.
Conclusion: The alignment of epidemiological and genetic evidence reinforces the likely causal, protective role of vitamin D in liver cancer. Genetic polymorphisms offer a means to reduce confounding, providing more robust evidence than observational data alone. Future research should emphasize large-scale randomized controlled trials of VD supplementation in high-risk groups and further investigation of gene-environment

Enhancing Anti-PD-1 Antibody Treatment in Colorectal Cancer: The Contribution of Innovative Immune Boosters and Inhibiting the USP2-PD-L1 Pathway

https://doi.org/10.22034/thr.2025.236684

Sarhang Hasan Azeez

Abstract Background: Colorectal cancer (CRC) remains a major global health issue, with advanced stages difficult to treat. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have improved cancer care, but they work well only in a small group of CRC patients with high microsatellite instability (MSI-H). Most CRC cases are microsatellite stable (MSS) and do not respond to ICI treatment alone, highlighting the need for combined therapies.
Methods: This review summarizes recent studies from PubMed, Google Scholar, and clinical trial databases up to 2025 focusing on why CRC resists ICI treatment. It examines ways to modify the immunosuppressive tumor microenvironment (TME), including using immune-boosting agents and targeting proteins like USP2 that regulate PD-L1.
Results: The immunosuppressive TME in MSS-CRC limits the effectiveness of PD-1 blockers. Immune adjuvants, such as the peptide NCL-P2, can reshape the TME by activating immune cells, increasing T cell entry into tumors, and reducing T cell exhaustion. Additionally, recent studies show that USP2 helps stabilize PD-L1 in cancer cells. Blocking USP2 leads to PD-L1 breakdown, improving T cell attack and boosting anti-PD-1 therapy in lab studies.
Conclusion: Combining anti-PD-1 antibodies with treatments that alter the immunosuppressive TME—such as immune adjuvants to strengthen immune responses and USP2 inhibitors to lower PD-L1 levels—offers a promising multi-target strategy. This method could help overcome treatment resistance and extend immunotherapy benefits to more CRC patients.

Exploring the Causal Role of Immune Cells in Autoimmune Hepatitis: A Narrative review of Mendelian Randomization Insights

https://doi.org/10.22034/thr.2025.236688

Sarhang Hasan Azeez

Abstract Background: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease with an incompletely understood etiology. Observational studies suggest dysregulated immunity, but confounding and reverse causation have hindered causal inference. Mendelian randomization (MR) uses genetic variants as instrumental variables to assess causality and has recently been applied to investigate immune involvement in AIH.
Objective: To summarize and interpret findings from a recent bidirectional two-sample MR study evaluating the causal effects of 731 immune cell traits on AIH risk, contextualizing them within existing immunological knowledge.
Methods: This narrative review focuses on a key MR investigation using genome-wide association study (GWAS) summary statistics for 731 immunophenotypes and AIH. The primary analysis method was inverse variance weighting, supplemented by sensitivity analyses (MR-Egger, weighted median) and reverse MR to assess robustness and directionality of causal relationships.
Conclusion: The MR analysis provides genetic evidence supporting a causal role for specific innate and adaptive immune cell subsets in AIH pathogenesis. These findings highlight the therapeutic potential of targeting pathways involving myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), dendritic cells, NKT cells, and the PD-1/PD-L1 axis, offering a foundation for future mechanistic and translational research.
 

Current Insights into Pathophysiology, Clinical Presentation, and Minimally Invasive Management of Renal Peripelvic Cysts, A Narrative Review

https://doi.org/10.22034/thr.2025.563719.1031

Shahabaldin Bagheri, Behkam Rezaiemehr, Mojtaba Yousefi Zoshk, Masoud Maboudi, Amirsaleh Abdollahi, Mehdi Younesi Rostami, Mohammad Javad Bay, Ahmad Deylami

Abstract Background: Renal peripelvic (parapelvic) cysts cause hydronephrosis, pain, and obstruction when exceeding 4-5 cm due to hilar compression, with elevated IL-6, TNF-α, and creatinine reflecting inflammation and impaired function.​
Objective: This narrative review synthesizes evidence on pathophysiology, diagnosis, and minimally invasive management, emphasizing retroperitoneoscopic decortication versus ureteroscopic drainage outcomes.​
Methods: Literature from 2011-2025 (PubMed, Scopus, Web of Science) was reviewed, prioritizing comparative studies, case series (n≥20), and biomarker data; a key 100-patient cohort provided head-to-head analysis.​
Results: Retroperitoneoscopic decortication shows superior outcomes versus ureteroscopy: shorter operative time (78±18 vs 112±24 min), less blood loss (25±15 vs 55±30 mL), faster recovery (hospital stay 2.8±0.9 vs 5.1±1.4 days), lower complications (8% vs 18%), and greater IL-6/TNF-α decline; recurrence rates similar (8-10%).​
Conclusion: Retroperitoneoscopic decortication is optimal for symptomatic peripelvic cysts, balancing efficacy, safety, and biomarker recovery over ureteroscopy

A Comparative Analysis of Primary Radiotherapy versus Transoral Surgery for Early-Stage Laryngeal Squamous Cell Carcinoma: Oncologic and Functional Results

https://doi.org/10.22034/thr.2025.236666

Feruza Ruzimova, Sevara Sadullayeva, Madrimov Javoxir Islombek o'g'li, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O'ktamovich, Xudoynazarova Dilnura, Uktamova Shoxida, Seyed Mohammad Hossein Mousavi

Abstract Backgrounds: Early-stage laryngeal squamous cell carcinoma (LSCC), which includes stage I and II disease, has a high cure rate. The main treatment approaches are definitive radiotherapy (RT) and transoral surgery (TOS), which includes transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). Selecting the optimal treatment involves balancing oncologic effectiveness with functional results and quality of life.
Objective: To review and compare current evidence on overall survival (OS), disease-specific survival (DSS), laryngeal preservation (LP), and functional outcomes in early-stage LSCC treated with primary RT or TOS.
Methods: A narrative literature review was performed, identifying relevant studies from PubMed and Scopus. The focus was on peer-reviewed articles from the last two decades, including retrospective cohort studies, prospective trials, systematic reviews, and meta-analyses that directly compared RT and TOS.
Results: Recent large-scale analyses and meta-analyses show similar overall and disease-specific survival rates for T1 and T2 tumors treated with modern TOS or RT. The main differences are seen in patterns of oncologic control. TOS is linked to lower local recurrence but a higher incidence of second primary tumors, whereas RT shows higher local recurrence but a lower need for salvage laryngectomy, resulting in comparable long-term laryngeal preservation rates. Functionally, TOS offers advantages in treatment duration, voice outcomes for select T1a lesions, and cost-effectiveness, but may lead to poorer swallowing outcomes for larger resections. RT may provide better voice quality for more extensive T1 and T2 lesions but carries risks of long-term dry mouth and tissue scarring.
Conclusion: Both RT and TOS are effective treatments for early-stage LSCC, with similar long-term survival outcomes. Treatment selection should be individualized, based on tumor characteristics, patient health, institutional experience, and patient preferences regarding functional trade-offs and treatment burden.

Osteoporosis: Pharmacological Treatments, Pain Management, and Their Implications for Clinical Practice

Pages 1-8

https://doi.org/10.22034/thr.2025.509428.1006

Mostafa Shahrezaee, Mohsen Chamanara, Seyed Sadegh Shirdel, Hosein Meskar, Sadegh Taheri, Amin Ghanbarpour Juybari, Goli Aezzi, Mehran Frouzanian, Amirsaleh Abdollahi

Abstract Introduction: Osteoporosis is a widespread bone disease characterized by low bone mineral density (BMD), structural bone deterioration, and an increased risk of fractures. It primarily affects postmenopausal women and the elderly, representing a significant global health burden. The management of osteoporosis involves pharmacological treatments aimed at preventing fractures, alleviating symptoms, and improving overall quality of life.
Methods: This review analyzes the pharmacology of current osteoporosis treatments, including bisphosphonates, selective estrogen receptor modulators (SERMs), monoclonal antibodies, and newer agents such as sclerostin inhibitors. It also examines pain management strategies, particularly those targeting fracture-related pain, and explores the intersection between bone therapies and analgesia.
Results: The current pharmacological treatments for osteoporosis have shown significant efficacy in reducing fracture risk. However, managing pain in osteoporosis, particularly post-fracture pain, remains a complex challenge. This review highlights the need for a multidimensional approach that integrates both bone-targeted therapies and effective pain management strategies.
Conclusion: While osteoporosis therapies have greatly reduced fracture risk, pain management in osteoporosis patients remains an area requiring further research. This review synthesizes current literature on osteoporosis treatments and pain management, offering insights into best practices and identifying future research directions to improve patient outcomes.

The Influence of Exercise-Based Cardiac Rehabilitation on Biomarker Profiles in Coronary Heart Disease

https://doi.org/10.22034/thr.2025.236680

Saber Abbaszadeh, Abdrimova Rayhon, Atajanov Adilbek Yuldashevich, Allabergan Sharipov, Salar Khazeni Fard

Abstract Background: Coronary Heart Disease (CHD) is a widespread health challenge characterized by intricate pathophysiological mechanisms such as chronic inflammation, endothelial impairment, and metabolic irregularities. Exercise-focused Cardiac Rehabilitation (CR) is a key element of secondary prevention, known to decrease mortality and improve health outcomes. Examining its impact on a diverse range of biomarkers offers deeper insight into the biological mechanisms behind these benefits.
Objective: This systematic review consolidates current research on the effects of structured exercise training within CR on biomarkers related to critical pathological areas in CHD patients, including inflammation, lipid metabolism, vascular function, myocardial stress, and metabolic health.
Methods: A systematic search of PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was conducted from January 2000 to May 2024. Randomized controlled trials, meta-analyses, and prospective cohort studies evaluating the impact of exercise-based CR on biomarkers in adults with confirmed CHD were included.
Results: Analysis of 40 high-quality studies shows that exercise-based CR consistently produces beneficial changes across multiple biomarker pathways. Notable findings include significant decreases in high-sensitivity C-reactive protein (median reduction of 32%), interleukin-6, and tumour necrosis factor-alpha; improved lipid profiles (increase in HDL-C of 5–10%, reduction in triglycerides of 15–20%); better endothelial function (increase in Flow-Mediated Dilation of 1.5–3.0%); lower myocardial stress (NT-proBNP reduction of 25–40%); and enhanced insulin sensitivity (HOMA-IR reduction of 15–30%).
Conclusion: Exercise training within CR exerts extensive, multisystem biological effects that directly address core CHD pathophysiological processes. The consistent favorable changes in biomarkers provide a strong mechanistic rationale for the known clinical benefits of CR and support the use of biomarker assessment to tailor risk stratification and improve secondary prevention approaches.

The Role of Risk Assessment in ICU Nosocomial Infection Management: A Comprehensive Review of Clinical Outcomes and Biomarker Dynamics

https://doi.org/10.22034/thr.2025.236689

Trupti Rekha Pradhan

Abstract Background: Nosocomial infections remain a significant challenge in intensive care units (ICUs), contributing to increased morbidity, mortality, and healthcare costs. Emerging evidence suggests that structured risk assessment strategies may not only improve infection control but also modulate inflammatory and immune responses.
Methods: A comprehensive literature review was conducted, querying PubMed, Cochrane Library, EMBASE, and Web of Science for studies published through 2025. Eligible studies evaluated risk assessment tools or protocols in ICU settings and reported on outcomes including infection incidence, clinical parameters, and biomarker levels (e.g., inflammatory cytokines).
Results: The integration of structured risk assessment frameworks into ICU infection prevention protocols is associated with substantial benefits. These include reduced infection rates, improved clinical outcomes, and favorable alterations in key biomarker profiles, indicating a potential systemic immunomodulatory effect.
Conclusion: Implementing risk assessment in ICU infection control is advantageous for both clinical outcomes and biomarker patterns. Future research should focus on longitudinal biomarker monitoring and the development of personalized, dynamic risk assessment models to further optimize prevention strategies.




 
 
 
 
 

The Role of Plasma Metabolites and Biomarkers in Esophageal Cancer

https://doi.org/10.22034/thr.2025.236678

Najmeh Mahmoudian Barezi, Feruza Ruzimova, Xulkar Kasimova, Aygerim Sisenbayevna Saginova, Niginabonu Khajiqurbonova, Maksadbek Babajanov

Abstract Background: Esophageal cancer (EC) is a highly aggressive malignancy with increasing global prevalence, especially esophageal adenocarcinoma (EAC). Late-stage detection significantly contributes to its unfavorable outcomes, highlighting an urgent demand for non-invasive early diagnostic approaches. Metabolomics, the comprehensive study of small-molecule metabolites, provides a valuable strategy for discovering biomarker patterns that mirror the pathophysiological condition of cancer.
Objective: This review seeks to consolidate and critically assess existing research on the utility of plasma metabolites as diagnostic, prognostic, and predictive biomarkers in EC.
Methods: A systematic search of PubMed, Scopus, and Web of Science was performed for literature published between January 2000 and March 2024. Keywords such as "esophageal cancer," "metabolomics," "plasma," "serum," "biomarkers," "mass spectrometry," and "NMR" were employed. Studies were chosen based on their focus on plasma or serum metabolomic analysis in human EC patients.
Results: EC patients exhibit consistent changes in plasma metabolomic profiles compared to healthy individuals. Major disrupted pathways involve amino acid metabolism (e.g., increased branched-chain amino acids, reduced glutamine), energy metabolism (including the Warburg effect and disturbances in the TCA cycle), and lipid metabolism (alterations in phospholipid and sphingolipid concentrations). Panels comprising multiple metabolites show strong diagnostic performance, often with area under the curve (AUC) values above 0.90. Additionally, certain metabolic patterns may be useful for predicting patient outcomes and evaluating responses to neoadjuvant treatments.
Conclusion: Plasma metabolomics offers considerable potential to transform the clinical approach to EC through non-invasive methods for early diagnosis, risk assessment, and therapy evaluation. Validation through extensive, multi-center prospective studies is needed to implement these advances in clinical settings.

The Evolving Relationship: Impact of Combined Radiotherapy and Temozolomide Treatment on Critical Biomarkers in Glioblastoma Multiforme Patients; A Comprehensive Analysis

https://doi.org/10.22034/thr.2025.236676

Babak Olia, Feruza Ruzimova, Atajanov Adilbek Yuldashevich, Madrimov Javoxir Islombek o'g'li, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O‘Ktamovich, Xudoynazarova Dilnura, Jalolbek Doschanov, Mahdi Hazratgholi

Abstract Background: The established first-line treatment for newly diagnosed Glioblastoma Multiforme (GBM) involves maximal surgical removal of the tumor, followed by a regimen of radiotherapy (RT) together with concurrent and maintenance temozolomide (TMZ) chemotherapy. Patient response to this combined approach varies widely and is closely associated with the tumor's molecular characteristics.
Objective: This analysis compiles current research on how the RT/TMZ combination modifies crucial GBM biomarkers over time, focusing on therapy-induced alterations rather than their initial prognostic significance.
Methods: A systematic review of literature from January 2000 to July 2024 was performed using PubMed, Scopus, and Web of Science. Search keywords included "glioblastoma," "radiotherapy," "temozolomide," "MGMT," "IDH," "biomarker," and related terms. Emphasis was placed on clinical trials and key preclinical studies.
Results: The RT/TMZ protocol imposes significant selective pressure, dynamically influencing GBM biomarkers. MGMT promoter methylation is the primary predictor of TMZ efficacy, but treatment often leads to the expansion of MGMT-active, resistant tumor clones at recurrence. IDH1/2 mutations are strong prognostic indicators, and their associated metabolic changes may increase tumor sensitivity to DNA-damaging therapies. Treatment substantially reshapes the tumor immune microenvironment; RT can stimulate anti-tumor immune responses but also increase PD-L1 expression, while TMZ often causes severe lymphocyte depletion. Additionally, therapy promotes the selection of cells with enhanced DNA damage repair mechanisms and activates survival pathways such as EGFR, fostering treatment resistance.
Conclusion: RT and TMZ induce continuous, adaptive changes in GBM biomarkers. Recognizing this dynamic process is essential for personalizing treatment, assessing response, and developing new combination therapies to combat resistance.

Targeted Antimicrobial Therapy in Urosepsis: A Review of Clinical Evidence and Inflammatory Marker Dynamics

https://doi.org/10.22034/thr.2025.557936.1020

Behkam Rezaiemehr, Reza Laripour, Ahmad Alikhani, Mohsen Yadollahi, Amirsaleh Abdollahi, Mehdi Younesi Rostami, Ahmad Deylami

Abstract Urosepsis is a severe, life-threatening condition caused by the rapid dissemination of urinary-tract pathogens into the bloodstream and an uncontrolled host inflammatory response. The emergence of multidrug-resistant organisms and the variability of immune activation in critically ill patients have made its management increasingly complex. Targeted antimicrobial therapy (TAT)—defined as the selection of antibiotics based on microbiological identification and susceptibility testing—embodies the principles of precision medicine, aiming to optimize treatment effectiveness while minimizing broad-spectrum exposure and the spread of resistance.

This review synthesizes the current evidence regarding the role of TAT in urosepsis, highlighting its effects on systemic inflammation, organ function, and clinical outcomes. Special attention is given to novel biomarkers such as Presepsin, neutrophil CD64 index, and Copeptin, examined alongside classical inflammatory mediators including tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP). Collectively, these markers provide valuable insights into the interplay between pathogen control and immune modulation. The review also discusses diagnostic and operational barriers to implementing TAT, the variability of antimicrobial stewardship across institutions, and future research directions aimed at integrating biomarker-guided targeted therapy into individualized sepsis management.

Ketamine for Acute Pain in the ED: Mechanisms, Protocols, and Safety Considerations

https://doi.org/10.22034/thr.2025.237240

Hossein Meskar, Ramin Razavi, Ali Zarei, Goli Aezzi Pashakollaei, Mostafa Jamali Jehizdani, Keihan Shabankhani

Abstract Background: Acute pain is one of the most frequent presenting complaints in emergency departments (EDs). In the context of the global opioid crisis, there is increasing interest in effective non-opioid and opioid-sparing analgesic strategies. Ketamine, at subanesthetic doses, has emerged as a valuable option for acute pain management due to its unique pharmacologic profile.
Objectives: This narrative review aims to synthesize current evidence on the mechanisms of analgesia, clinical efficacy, dosing protocols, and safety considerations of ketamine for acute pain management in adult ED patients.
Methods: A comprehensive narrative review of the literature was conducted using recent randomized controlled trials, systematic reviews, meta-analyses, and international guidelines focusing on ketamine use for acute pain in emergency settings. Studies from diverse geographic regions and healthcare systems were included to provide a global perspective.
Results: Evidence consistently demonstrates that subdissociative-dose ketamine provides analgesia comparable to opioids for acute pain in the ED. Typical intravenous doses of 0.1–0.35 mg/kg, administered as a bolus or infusion, achieve rapid pain relief while preserving respiratory drive and airway reflexes. Ketamine is associated with higher rates of transient neuropsychiatric effects, such as dizziness and emergence reactions, but lower risks of respiratory depression compared with opioids. Alternative routes of administration, including intranasal and subcutaneous, offer additional flexibility in selected patients.
Conclusion: Ketamine is a safe and effective alternative or adjunct to opioids for acute pain management in the emergency department when used at appropriate subanesthetic doses. With proper patient selection, monitoring, and adherence to established protocols, ketamine can play a central role in multimodal ED analgesia strategies aimed at improving pain control while reducing opioid exposure.

The Impact of Chemoradiation Therapy on Serum Biomarkers in Breast Cancer Patients: A Review of Prognostic and Predictive Dynamics

https://doi.org/10.22034/thr.2025.236683

Babak Olia, Uktamova Shoxida, Quralbayeva Kumushoy, Niginabonu Khajiqurbonova, Fayzullayev Umidjon O'ktamovich, Ulliyeva Rayxon, Mirjalol Madaminov, Seyed Mohammad Hossein Mousavi

Abstract Background: Chemoradiation therapy (CRT) is fundamental for treating locally advanced and high-risk breast cancer. Although effective, it significantly impacts systemic physiology, which can be tracked through fluctuations in serum biomarkers. This review consolidates existing research on how CRT affects circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), inflammatory cytokines, and tissue injury markers, assessing their value for predicting outcomes and guiding treatment.
Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted for studies to 2025. Keywords included "breast cancer," "chemoradiation," "serum biomarker," "ctDNA," "CTC," and related terms. Eligible studies reported serum biomarker levels in breast cancer patients before, during, or after CRT and linked them to clinical results.
Results: Analysis of studies indicates that CRT causes a predictable but individualized alteration in serum biomarkers. A swift decrease in CTCs and ctDNA levels during neoadjuvant or definitive CRT strongly correlates with pathological complete response (pCR) and better survival. In contrast, detectable ctDNA after treatment is a powerful indicator of minimal residual disease (MRD) and impending relapse. Inflammatory markers such as IL-6 and CRP generally increase during therapy; prolonged elevation is linked to poorer prognosis and greater toxicity. Additionally, biomarkers like high-sensitivity Troponin I and TGF-β1 enable early identification of subclinical cardiotoxicity and radiation-induced skin damage, respectively.
Conclusion: Serum biomarkers offer a real-time, dynamic reflection of tumor response and host toxicity during CRT. Incorporating liquid biopsy components (CTCs, ctDNA) and host-response markers into clinical practice shows great potential for personalizing treatment, facilitating early intervention, and enhancing long-term results. Prospective studies are urgently required to standardize testing methods and confirm their clinical utility in guiding treatment strategies.