With the widespread use of antiretroviral therapy (ART), the lifespan of individuals infected with human immunodeficiency virus (HIV) has been significantly prolonged; however, the prevalence of HIV-associated neurocognitive disorder (HAND) has not decreased correspondingly. Cytomegalovirus (CMV), as a latent opportunistic pathogen, is prevalent among HIV-infected individuals. Co-infection of CMV and HIV may exacerbate neurological damage through synergistic effects and has become a key factor affecting the long-term quality of life and prognosis of patients. This article aims to systematically elucidate the virological and immunological basis, molecular and cellular mechanisms, clinical phenotypes, diagnostic strategies, and therapeutic management of neurological damage caused by HIV and CMV co-infection, and to summarize the latest research progress and future directions, providing an integrated perspective for clinical practice and scientific research.

Obesity represents one of the most critical global public health challenges. Pancreatic lipase (PL) serves as a key therapeutic target for obesity control, whereas clinical synthetic PL inhibitors are greatly restricted by adverse reactions. Traditional Chinese medicines (TCMs) have a long-standing history in regulating lipid metabolism and ameliorating obesity-related disorders, and are characterized by remarkable structural diversity, low toxicity, and mild side effects, thus representing a promising source for developing safe and efficient PL inhibitors. In this work, an integrated strategy combining in silico screening and in vitro validation was employed to identify potential PL inhibitors from TCM components, including molecular docking, molecular dynamics simulation, MM/PBSA binding free energy computation, and in vitro enzymatic assay. Six compounds with docking scores ranging from −9.9 to −9.0 kcal/mol were selected for further investigation. Molecular dynamics simulations verified the favorable structural stability of the corresponding ligand–PL complexes, and MM/PBSA calculations demonstrated negative binding free energies from −21.24 ± 0.39 to −12.03 ± 0.40 kcal/mol. In vitro experiments indicated that three compounds (Hydroxygenkwanin, Atractylenolide I, and Peiminine) showed effective PL inhibitory activity, with IC50 values of 0.128 ± 0.009, 0.584 ± 0.031, and 0.748 ± 0.042 mM, respectively. These values are comparable to quercetin (0.231 ± 0.034 mM) but significantly higher than orlistat (0.481 ± 0.023 μM), which is attributed to their non-covalent binding pattern. Collectively, this study validated the reliability of the integrated in silico and in vitro screening strategy, identified three effective pancreatic lipase inhibitors derived from TCMs, established a robust paradigm for the discovery of natural PL inhibitors, and laid a solid foundation for subsequent research on natural anti-obesity agents.

Obesity is one of the major global public health challenges. Pancreatic lipase (PL) is an important target for obesity management as it plays a key role in lipid absorption. However, the clinical application of synthetic PL inhibitors is limited by adverse effects. Previous studies showed that natural products from traditional Chinese medicines (TCMs) is a promising alternative for developing safe PL inhibitors. In this study, we integrated molecular docking, molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations and in vitro enzymatic assays to systematically screen potential PL inhibitors from TCM constituents. Six compounds with docking scores ranging from −9.9 to −9.0 kcal/mol. MD simulations confirmed the structural stability of six ligand−PL complexes via RMSD, radius of gyration (Rg), hydrogen bond and conformational analysis. MM/PBSA calculations revealed the binding free energies of the six compounds to PL ranged from −21.38±0.40 to −13.33±0.58 kcal/mol. In vitro validation showed five of the six compounds exhibited PL inhibitory activity, among which Hydroxygenkwanin (HYD) was the most potent competitive inhibitor (IC₅₀= 0.128±0.009 mM), followed by Atractylenolide I (ATR-I) (IC50 = 0.584±0.031 mM) and Peiminine (PEI) (IC50 = 0.748±0.042 mM). This study validates the efficiency of the integrated in silico and in vitro strategy for screening natural PL inhibitors and provide valuable reference for the development of novel anti-obesity agents or functional food ingredients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis. Synovial fibroblasts (SF) are the predominant cellular components in the inflamed synovium. Recent studies have shown increased expression of P2X7 receptor (P2X7R) in RA SF. However, its precise expression patterns and its contribution to inflammatory arthritis remain unclear. We demonstrate that P2X7R is robustly expressed in RA synovium, correlating with increased synovitis and systemic inflammation. Single-cell transcriptome analysis indicated that P2X7R was enriched in specific SF associated with refractory RA. Then, we applied a highly selective human P2X7R antagonist, EVT-401, which promoted apoptosis and induced cell cycle arrest in RA SF, reduced the production of proinflammatory and joint-destructive mediators, and mitigated aggressive phenotypes. Furthermore, we demonstrated that EVT-401 markedly reduced synovial inflammation and arthritis severity in a nonhuman primate model of autoimmune arthritis. Together, these findings suggest that P2X7R is involved in synovial inflammation and its inhibition may represent a potential therapeutic strategy for refractory RA.

Background/Objectives: HPV status is a key prognostic determinant in head and neck squamous cell carcinoma (HNSCC), yet the immunological mechanisms underlying the survival advantage of HPV-positive (HPV+) over HPV-negative (HPV-) disease remain poorly defined. This study aimed to characterize the tumor-infiltrating natural killer (NK) cell landscape in HPV-stratified HNSCC and identify novel therapeutic targets. Methods: We performed an NK-cell-centric re-analysis of published scRNA-seq data from 28 HNSCC patients (10 HPV+, 18 HPV-; GEO: GSE139324, GSE164690), encompassing NK subset identification, pseudotime trajectory inference, and cell-cell interaction analysis. Key findings were validated by immunohistochemistry (IHC) in an independent cohort of 10 FFPE tissue sections, and prognostic associations were assessed using TCGA-HNSC data. Results: Four transcriptionally distinct NK cell subsets were identified: adaptive, cell-killing, CD56bright, and virus-responsive. A cytotoxic CX3CR1+KLRB1dim NK subset was specifically enriched in HPV+ tumors and independently associated with favorable survival. Conversely, HPV- tumors upregulated CLEC2C and CLEC2D ligands on tumor cell surfaces, engaging the inhibitory receptor KLRB1 on NK cells; this CLEC2-KLRB1 axis correlated with suppressed NK activity and poorer prognosis, and was confirmed at the protein level by IHC. Conclusions: NK cell function in HNSCC is dichotomously regulated by HPV status. The CX3CR1+KLRB1dim subset represents a candidate prognostic biomarker in HPV+ disease, and the CLEC2-KLRB1 axis is a targetable immune evasion mechanism in HPV- HNSCC. These insights support the development of HPV-stratified immunotherapies; however, clinical translation requires validation in large, prospectively designed, subsite-matched cohorts to disentangle HPV-specific effects from anatomical site-dependent immune contextures.

Background Mucosal healing is a major clinical challenge and a critical prognostic factor in inflammatory bowel disease (IBD). Achieving mucosal healing requires the functional reprogramming of macrophages to facilitate intestinal stem cells (ISCs)-mediated repair, a process impaired in IBD due to dysregulated macrophage activity. Dihydroartemisinin (DHA), a derivative of artemisinin, shows promise in treating IBD, but its therapeutic potential remains underexplored due to its common classification as an anti-inflammatory agent. Purpose This study aims to evaluate the efficacy of DHA in promoting mucosal healing in IBD and to elucidate the underlying mechanisms of macrophage reprogramming, thereby expanding the therapeutic potential of DHA beyond its conventional anti-inflammatory actions. Methods The therapeutic efficacy of DHA and its underlying mechanisms were systematically investigated using a DSS-induced colitis mouse model, with a focus on the repair phase. Mucosal healing was assessed through comprehensive histopathological and functional evaluations. DHA’s role in macrophage metabolic reprogramming was explored through transcriptomic and metabolic analyses, and its effect on epithelial regeneration was examined using macrophage-organoid co-cultures. A molecular target discovery approach, integrating Mendelian randomization, molecular docking, and direct binding assays, identified 11βHSD-1 as a molecular target of DHA, which was subsequently confirmed through genetic and pharmacological loss-of-function studies in macrophages. Results Our findings demonstrated that DHA significantly promoted mucosal healing in a DSS-induced colitis model during the repair phase, as evidenced by reduced disease activity scores, increased colon length, and decreased histological damage. DHA also facilitated the recovery of gut functions, including barrier integrity, absorption, secretion, and motility. Macrophages were found to be essential for therapeutic effects of DHA. Specifically, DHA reprogrammed macrophage metabolism from glycolysis to oxidative phosphorylation, inducing a pro-repair phenotype characterized by enhanced secretion of Relmα and Wnt3a, which promoted the proliferation and differentiation of intestinal organoids. Mechanistically, we found that DHA directly bound to and activated 11βHSD-1, a key metabolic regulator in macrophages. This activation triggered STAT3/6 signaling, establishing a positive feedback loop that reinforced metabolic remodeling and facilitated the release of repair-promoting factors. Conclusion Our findings demonstrate that DHA promotes intestinal mucosal healing by reprogramming macrophage metabolism, thereby enhancing ISC proliferation and differentiation. These results provide new insights into the potential of DHA in reshaping immune homeostasis, offering promising therapeutic strategies for IBD.

Background: Mucosal healing is a major clinical challenge and a critical prognostic factor in inflammatory bowel disease (IBD). Achieving mucosal healing requires the functional reprogramming of macrophages to facilitate intestinal stem cells (ISCs)-mediated repair, a process impaired in IBD due to dysregulated macrophage activity. Dihydroartemisinin (DHA), a derivative of artemisinin, shows promise in treating IBD, but its therapeutic potential remains underexplored due to its common classification as an anti-inflammatory agent. Purpose: This study aims to evaluate the efficacy of DHA in promoting mucosal healing in IBD and to elucidate the underlying mechanisms of macrophage reprogramming, thereby expanding the therapeutic potential of DHA beyond its conventional anti-inflammatory actions. Methods: The therapeutic efficacy of DHA and its underlying mechanisms were systematically investigated using a DSS-induced colitis mouse model, with a focus on the repair phase. Mucosal healing was assessed through comprehensive histopathological and functional evaluations. DHA's role in macrophage metabolic reprogramming was explored through transcriptomic and metabolic analyses, and its effect on epithelial regeneration was examined using macrophage-organoid co-cultures. A molecular target discovery approach, integrating Mendelian randomization, molecular docking, and direct binding assays, identified 11(3HSD-1 as a molecular target of DHA, which was subsequently confirmed through genetic and pharmacological loss-of-function studies in macrophages. Results: Our findings demonstrated that DHA significantly promoted mucosal healing in a DSS-induced colitis model during the repair phase, as evidenced by reduced disease activity scores, increased colon length, and decreased histological damage. DHA also facilitated the recovery of gut functions, including barrier integrity, absorption, secretion, and motility. Macrophages were found to be essential for therapeutic effects of DHA. Specifically, DHA reprogrammed macrophage metabolism from glycolysis to oxidative phosphorylation, inducing a pro-repair phenotype characterized by enhanced secretion of Relm alpha and Wnt3a, which promoted the proliferation and differentiation of intestinal organoids. Mechanistically, we found that DHA directly bound to and activated 11 beta HSD-1, a key metabolic regulator in macrophages. This activation triggered STAT3/6 signaling, establishing a positive feedback loop that reinforced metabolic remodeling and facilitated the release of repair-promoting factors. Conclusion: Our findings demonstrate that DHA promotes intestinal mucosal healing by reprogramming macrophage metabolism, thereby enhancing ISC proliferation and differentiation. These results provide new insights into the potential of DHA in reshaping immune homeostasis, offering promising therapeutic strategies for IBD.

Background: Human papillomavirus (HPV) infection defines a distinct subtype of head and neck squamous cell carcinoma (HNSCC). Although HPV-positive (HPV+) HNSCC generally shows better overall survival than HPV-negative (HPV-) disease, it is frequently associated with cervical lymph node metastasis. However, the epithelial cell states and viral gene-associated mechanisms underlying HPV-related metastatic progression remain incompletely understood. This study aimed to identify metastasis-associated epithelial subpopulations in HPV+ HNSCC and explore the potential role of HPV16 E7 in regulating metastatic programs. Methods: Public single-cell RNA-sequencing datasets from paired primary and metastatic HNSCC samples were integrated and analyzed to characterize malignant epithelial subpopulations. Copy number variation (CNV) inference, clustering, pathway enrichment, stemness scoring, and trajectory analysis were performed to define metastasis-associated epithelial states. TCGA transcriptomic data and tissue-based validation were used to support candidate gene screening. In vitro functional assays were performed using SERPINB3-knockdown and HPV16 early gene-overexpressing CAL27 cell models. Results: Single-cell analysis identified stem-like metastatic epithelial subpopulations in HPV+ and HPV- HNSCC. In HPV+ metastatic lesions, an ALDH2+/LAMB3+ epithelial subpopulation showed elevated epithelial-mesenchymal transition activity and stem-like features. SERPINB3 displayed a dynamic expression pattern during HPV+ metastatic progression. Functional assays showed that SERPINB3 knockdown enhanced CAL27 cell migration and invasion and was associated with activation of MYC- and epithelial-mesenchymal transition-related transcriptional programs. Among HPV16 early genes, E5, E6, E6*, and E7 showed different degrees of SERPINB3 suppression, while E7-expressing cells exhibited distinct transcriptional alterations associated with epithelial plasticity and metastatic-related programs. Conclusions: This study identifies a stem-like metastatic epithelial state in HPV-associated HNSCC and suggests a potential HPV16 early gene-SERPINB3-MYC-related regulatory mechanism involved in metastatic epithelial plasticity.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Massive cohort studies revealed that AD was associated with allergic diseases, inflammatory diseases, autoimmune diseases, cardiovascular diseases, and mental disorders. We comprehensively and systematically analyzed the correlation between AD and diseases to identify AD-associated diseases (ADADs). We involved 17,924 individuals from the National Health and Nutrition Examination Survey (NHANES) (2013-2018) dataset, and analyzed the correlation between AD and 422 diseases classified by International Classification of Diseases-10 (ICD-10) using four logistic regression models. We found that AD is significantly associated with 33 diseases: (1) allergic diseases, including urticaria, allergic rhinitis, allergy, asthma, other seasonal allergic rhinitis; (2) inflammatory diseases, including noninfective gastroenteritis and colitis, acute atopic conjunctivitis, osteoarthritis, and unspecified chronic bronchitis; (3) mental disorders with impairment (MDI), including comorbid mental disorders, schizophrenia and sleep disorder; (4) malignant tumors, including malignant neoplasm of prostate, malignant (primary) neoplasm and malignant neoplasm of breast; (5) other symptoms and diseases, other symptoms and diseases, such as wheezing, pruritus and gout. Notably, non-infective gastroenteritis and colitis showed the strongest correlation (OR: 38.39, 95% CI: 3.08-478.01) among the 33 ADADs. We identified 33 ADADs based on the NHANES (2013-2018) dataset, which provide new insights into understanding the development of these ADADs associated with AD.

OBJECTIVE:Human cytomegalovirus (HCMV), a prevalent double-stranded DNA enveloped virus, poses a threat to immunocompromised individuals. The current clinical detection methods are insufficient in sensitivity, highlighting the need for more effective approaches. METHODS:We designed and screened RPA primers and crRNA based on the UL123 gene of HCMV. Evaluate the HCMV-RPA-CRISPR detection method using cloned plasmids and the whole-genome samples of HCMV-infected cells. Conduct RPA-CRISPR/Cas12a reactions with 48 clinical samples and compare the results with those of PCR-Fluorescent Probe Method in clinical applications and the qPCR method for detecting the UL123 gene. RESULTS:The optimized RPA-CRISPR system exhibited high sensitivity and specificity for HCMV detection. The positive rate of clinical sample detection was approximately 20.5 % (6/48) higher than that of the clinical detection method. CONCLUSION:Currently, the sensitivity and early detection of HCMV in clinical settings are still limited. The UL123 gene of HCMV is characterized by high transcription in the early stage and high conservation. The RPA-CRISPR/Cas12a technology exhibits high sensitivity in detecting the HCMV UL123 gene, and it is expected to provide a more effective method for the early specific detection of HCMV infection.

Berberine is an isoquinoline alkaloid, which has demonstrated significant therapeutic potential in the treatment of various diseases, including tumors, acute and chronic infections, autoimmune disorders, and diabetes. Studies have demonstrated that berberine exhibits polypharmacological effects, including antibacterial, anti-inflammatory, antioxidant, and hypoglycemic activities. To further elucidate the multifaceted pharmacological mechanisms of berberine, we reviewed 7 targets of berberine identified through co-crystal structure analysis, including filamentous temperature-sensitive protein Z (FtsZ), QacR, BmrR, phospholipase A2 (PLA2), RamR, NIMA-related kinase 7 (NEK7), and mesenchymal-epithelial transition (MET). Through target fishing, molecular docking, and surface plasmon resonance (SPR) analyses, combined with cellular and molecular experiments, we further identified 6 targets of berberine. These findings provide a comprehensive summary of berberine’s direct molecular targets, offering a theoretical foundation for further exploration of its diverse pharmacological activities.

Background:Organophosphate pesticides (OPPs) are widely used environmental chemicals with potential health impacts, but their relationship with atopic dermatitis (AD) remains unclear. Methods:Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2007, we investigated associations between urinary OPP metabolites and AD in 4,258 adults. Six dialkyl phosphate (DAP) metabolites were measured, and weighted quantile sum (WQS) regression was used to assess mixture effects. Results:Both DMP (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.05-1.31) and DMDTP (OR = 2.23, 95%CI: 1.08-4.60) showed significant positive associations with AD in fully adjusted models. WQS regression revealed significant associations between mixed OPP exposure and AD (OR = 1.25, 95%CI: 1.04-1.50), with DMP contributing most (45.8%) to the mixture effect. Stratified analyses indicated stronger associations in males, younger adults (<60 years), and smokers. Conclusion:Our findings suggest that OPP exposure, particularly DMP, may be associated with increased AD risk in adults. These results provide new insights into environmental risk factors for AD.

BACKGROUND Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy, affecting an estimated 17.7-40 per 100 000 population. CMT exhibits diverse clinical manifestations, including gradually progressive bilateral atrophy, weakness of the lower-extremity muscles, sensory abnormalities, and abnormal nerve conduction velocities or amplitudes. It is important to note that other complications tend to occur during the progression of CMT disease. This report describes the late diagnosis of CMT in a 53-year-old mother and her 24-year-old daughter to highlight the risk of CMT patients complicated with respiratory and digestive diseases. CASE REPORT In this report, we describe the late diagnosis of CMT1E in 2 patients who carried the same missense point mutation in the peripheral myelin protein 22 gene {PMP22; [c.117G>C; p.(Trp39Cys)]}. Case 1 (daughter), in addition to CMT1E, was also diagnosed with respiratory disorders, hiatal hernia, gastroesophageal reflux disease (GERD), and chronic atrophic gastritis. Similarly, Case 2 (mother), who was diagnosed with CMT1E, also had a hiatal hernia, GERD, and chronic atrophic gastritis. Our report emphasized a potential association between CMT and digestive diseases and provides new insights into the prognosis of CMT. CONCLUSIONS This report presents 2 cases of respiratory dysfunction and multiple digestive diseases in a 53-year-old mother and her 24-year-old daughter, with the late diagnosis of CMT. These findings emphasize the importance of comprehensive patient care and provide a reference for future research into multidisciplinary approaches to the diagnosis and treatment of CMT.

BACKGROUND:Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability. METHODS:A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods. RESULTS:Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate. CONCLUSIONS:This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice.

Background: Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This devastating complication may cause consistent pain and dramatically reduction of functionality. Unfortunately, the conservative treatments to prevent the AF in the early stage are largely unknown due to the lack of specific biomarkers and reliable therapeutic targets. Methods: In this study, we extracted1782 fibrosis related genes (FRGs) from 373,461published literature based on the large natural language processing models (ChatGPT) and intersected with the 2750 differential expressed genes (DEGs) from mRNA microarray (GSE135854). A total of 311 potential AF biomarker genes (PABGs) were obtained and functional analysis were performed including gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, we accomplished validation in AF animal models with immobilization of the unilateral knee joints of 16 rabbits for 1-week, 2-weeks, 3-weeks and 4-weeks. Finally, we tested the biomarkers in a retrospective cohort enrolled 35 AF patients and 35 control group patients. Results: We identified G-protein-coupled receptor 17 (GPR17) as a reliable therapeutic biomarker for AF diagnosis with higher AUC (0.819) in the ROC curve. A total of 21 potential drugs targeted to GPR17 were screened. Among them, pranlukast and montelukast have achieved therapeutic effect in animal models. In addition, we established an online AF database for data integration (https://chenxi2023.shinyapps.io/afdbv1). Conclusions: These results unveiling therapeutic biomarkers for AF diagnosis, and provide potential drugs for clinical treatment. The translational potential of this article: Our study demonstrated that GPR17 holds significant promise as a potential biomarker and therapeutic target for arthrofibrosis. Moreover, pranlukast and montelukast targeted to GPR17 that could be instrumental in the treatment of AF.

Introduction: Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD patients exhibit an increased incidence of oral disorders. In the present study, we sought mechanistic insights into how AD affects periodontitis. Methods: Onset of AD was induced by 2,4-dinitrochlorobenzene (DNCB). Furthermore, we induced periodontitis (P) in AD mice. The effect of AD in promoting inflammation and bone resorption in gingiva was evaluated. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunofluorescence assay, and flow cytometry were used to investigate histomorphology and cytology analysis, respectively. RNA sequencing of oral mucosa is used tissues to further understand the dynamic transcriptome changes. 16S rRNA microbial analysis is used to profile oral microbial composition. Results: Compared to control group, mice in AD group showed inflammatory signatures and infiltration of a proallergic Th2 (Th2A)-like subset in oral mucosa but not periodontitis, as identified by not substantial changes in mucosa swelling, alveolar bone loss, and TRAP(+) osteoclasts infiltration. Similarly, more Th2A-like cell infiltration and interleukin-4 levels were significantly elevated in the oral mucosa of DNCB-P mice compared to P mice. More importantly, AD exacerbates periodontitis when periodontitis has occurred and the severity of periodontitis increased with aggravation of dermatitis. Transcriptional analysis revealed that aggravated periodontitis was positively correlated with more macrophage infiltration and abundant CCL3 secreted. AD also altered oral microbiota, indicating the re-organization of extracellular matrix. Conclusions: These data provide solid evidence about exacerbation of periodontitis caused by type 2 dermatitis, advancing our understanding in cellular and microbial changes during AD-periodontitis progression.

The aim of this study is to evaluate the potential of lymphocytes as biomarkers to predict the decline of coronavirus disease 2019 (COVID-19). Lymphocytes were counted in 164 moderate COVID-19 patients in Shenzhen, China. Among the moderate infected patients, 12.2% (20/164) progressed to severe cases after admission. Compared with the stable patients, the counts of lymphocytes, both total T lymphocytes and CD4+ T lymphocytes, in the severe patients, were lower. The aggravation of moderate infected patients was significantly associated with lymphocyte count (hazard ratio [HR] = 0.91; 95% confidence interval [CI]: 0.84-0.99), total T lymphocyte count (HR = 0.91; 95% CI: 0.84-0.99), and CD4+ T lymphocyte count (HR = 0.91; 95% CI: 0.85-0.98). Total T lymphocytes and CD4+ T lymphocytes could be important biomarkers to evaluate the risk of aggravation for moderate infected COVID-19 patients. The patients with low percentages of total T lymphocytes and CD4+ T lymphocytes need more attention.

目的:旨在建立高效、可靠的实验方法以快速检测肿瘤浸润淋巴细胞(tumor-infiltrating lymphocyte,TIL)产品制备过程中多种细胞培养基辅料的潜在残留.方法:采用酶联免疫吸附法(enzyme-linked immunosorbent assays,ELISA)定量检测TIL产品中的庆大霉素、白介素2(interleukin-2,IL-2)和重组人胰岛素,重点验证检测方法的专属性、准确度、可重现性、精密度、定量限、线性、范围、耐用性等7个指标.结果:商业化ELISA试剂盒不受TIL注射液溶剂和上清液的干扰.使用各自标准品检测上述3种辅料的回收量与实际加标量的差异在30％以内,而且复孔读数的变异系数均＜10％.适用线性检测范围分别为0.3～6.0 ng·mL-1、31.3～2000.0 pg·mL-1、3.0～160.0 mIUg·L-1.待测TIL样本中庆大霉素、IL-2和重组人胰岛素残留浓度最高值分别为＜0.3 ng·mL-1、37.4 pg·mL-1和＜0.1 mIU·I.-1,均符合对应的放行标准.结论:现有ELISA试剂盒在检测3种培养基辅料残留时都具有良好的灵敏度、准确性和稳定性,可以快速定量分析TIL产品中是否含有潜在的杂质成分.

www.jogh.org • doi: 10.7189/jogh.13.03037 1 2023 • Vol. 13 • 03037 It is widely acknowledged that a comprehensive understanding of the risk factors associated with the disease is vital for both the general public and medical researchers [1,2]. For the population at large, understanding disease risk factors can enable informed decisions about lifestyle choices and preventative measures, thus contributing to overall health and well-being [3,4]. With knowledge of the disease risk factors, individuals can consciously strive to mitigate their risk, adopt healthier behaviours, and reduce the incidence of preventable diseases. For medical researchers, studying disease risk factors forms the basis of epidemiological investigations [5] that elucidates the complex aetiology of diseases, aiding in identifying causative and contributing factors; consequently, this guides the development of targeted therapeutic approaches, provides clinical guidelines, and drives innovative research on disease prevention and treatment [6]. Moreover, a comprehensive understanding of disease risk factors enables the conception of population-specific intervention strategies that contribute to health equity and the broader goal of global health improvement [7].

Charcot–Marie–Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described. We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model. Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32–24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06–14.64)] than for other subtypes (P’ < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions. CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support.