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摘要： To observe the effects of acupuncture on intestinal flora and inflammatory factor interleukin (IL)-6 in ulcerative colitis (UC) model rats and to explore the related mechanism of acupuncture in treating UC. Thirty-two Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model (MO) group, a mesalazine (ME) group, and an acupuncture (AC) group, with 8 rats in each group. Rats, except those in the NC group, were given a 2.5% sodium dextran sulfate solution to establish UC models. After successful modeling, rats in the ME group were treated with mesalazine by gavage twice a day for 7 continuous days; rats in the AC group received acupuncture at bilateral Tianshu (ST25) and Zusanli (ST36) with needles retained for 20 min each time, once a day for 7 consecutive days. After intervention, changes in the intestinal flora diversity, colon tissue damage degree, and inflammatory factor expression in each group of rats were evaluated. The body mass increased slowly in the MO group compared to the NC group. After intervention, the body mass increased more significantly, colon injuries recovered, and intestinal flora diversity improved in the ME and AC groups compared to the MO group (P<0.05). The IL-6 expression level was higher in the MO group compared to the NC group (P<0.05). The IL-6 expression level decreased in the AC group compared to the MO group (P<0.05). Acupuncture at Tianshu (ST25) and Zusanli (ST36) improves body mass loss and colon injuries, regulates intestinal flora diversity, and reduces the expression of inflammatory factor IL-6 in the colon tissue of UC rats, therefore alleviating the disease severity of UC.

关键词： Pars Plana vitrectomy   cytokines   epiretinal membrane   interleukin-6   rhegmatogenous retinal detachment  

摘要： Introduction:Epiretinal membrane (ERM) formation following a successful rhegmatogenous retinal detachment (RRD) operation has been reported to occur in about 4%-15% of the cases. In this study, we collected vitreous samples from patients with RRD to identify whether the concentration of IL-6 is correlated with the presence of postoperative ERM. We aim is to identify whether the inflammatory cascade could be a potential key factor in the ERM pathogenesis. Methods:This was a prospective single-centre study where 42 eyes were enrolled. All patients underwent 25G PPV. The vitreous sample was collected before the infusion line was opened so that the sample would not be diluted. Then, the sample was centrifuged at 5000 g for 15 min at 15°C. Afterwards, the supernatant fluid was transferred to an Eppendorf tube and stored at -40°C. Electrochemiluminescence immunoassay (ECLIA) was employed for the measurement of IL-6 concentration (pg/ml). All patients had optical coherence tomography (OCT) scans at the macula at 4 weeks, 3 months and 1 year after primary RRD repair to identify the presence of the ERM. Results:All patients had a follow-up of at least 12 months. The mean BCVA of all 42 eyes at the end of follow-up period was 0.24 ± 0.31 LogMar. The presence of ERM was identified in 28.6% ( = 12) of the patients, and the mean IL-6 concentration was 573.96 ± 1179.58 pg/ml. It appears that the patients who developed a post op ERM had an IL-6 mean concentration value of 173.96 ± 191.25 pg/ml, and the patients with no post op ERM had 733.97 ± 1364.04 pg/ml with -value = 0.04 < 0.05. Nevertheless, following a multivariate binary logistic regression model, the above results did not appear to be statistically significant. Conclusion:High concentration of IL-6 in the vitreous of eyes with RRD does not hold a significant role in the ERM pathogenesis. Our study identified the presence of a draining retinotomy as the most significant risk factor for ERM formation following a successful

关键词： Biomarkers   CTRP-1   Gingival crevicular fluid   Non-surgical periodontal therapy   Periodontal disease  

摘要： OBJECTIVES:This study investigated the gingival crevicular fluid (GCF) levels of complement-C1q tumor necrosis factor related protein-1 (CTRP-1), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) following non-surgical periodontal therapy (NSPT) in systemically healthy individuals with periodontal health (H), generalized gingivitis (G), and stage III grade B periodontitis (P). Moreover, this study aimed to investigate their diagnostic potential in distinguishing different periodontal diseases. MATERIALS AND METHODS:73 systemically healthy non-smoking individuals were divided into H (n = 25), G (n = 23) and P (n = 25) groups. Clinical periodontal parameters were recorded, and GCF samples were collected at baseline in all groups, and 3rd month after NSPT in the G and P groups. GCF levels of CTRP-1, TNF-α, and IL-10 were analyzed using ELISA. The area under the curve (AUC) was assessed using the receiver operating characteristic curve analysis. RESULTS:CTRP-1 levels were significantly elevated in the G and P group compared to the H group (p < 0.001), while there was no significant difference between the G and P groups (p = 0.095). TNF-α and IL-10 levels were significantly higher in the P group compared to the other groups (p < 0.001). GCF CTRP-1 demonstrated an excellent diagnostic performance to discriminate periodontitis and gingivitis from periodontal health (AUC value of 0.998 and 0.974 with 100% and 91.3% sensitivity). CONCLUSION:CTRP-1 could serve as a potential biomarker for periodontal diseases. CTRP-1 demonstrated excellent diagnostic performance in distinguishing stage III grade B periodontitis and gingivitis from periodontal health. CLINICAL RELEVANCE:GCF CTRP-1 levels may serve as a valuable marker for diagnosing periodontal diseases.

摘要： This study investigates the Kızılırmak and Yeşilirmak estuarine ecosystems in Turkey, which provide significant freshwater and nutrient inputs to the Samsun Shelf area along the midsouthern Black Sea. The objective was to determine the current ecological status and to detect any significant differences between two estuarine ecosystems (restored—Kızılırmak—and natural—Yeşilırmak) in terms of macrobenthic invertebrates and environmental variables. Macrobenthic invertebrates were collected with a 500 µm mesh size kick-net. A total of four samplings, one in each season, were collected during February, May, August, and November of 2017. A total of 90 taxa, mainly oligochaetas and chironomids, were identified, composed of 51 species in Kızılırmak and 60 in Yeşilırmak. Orthocladius (Orthocladius) dentifer, O. (O.) clarkei, O. (O.) dorenus, O. (O.) wetterenesis, O. (O.) mixtus, and Mystacides longicornis were found to be new records for Turkey. The distribution of macrobenthic invertebrates was compared between season, estuary, grain size and stations. In Kızılırmak and Yeşilırmak, the region characterized as estuarine was found to be small transitional waters. In Kızılırmak, a high similarity was observed among stations, accompanied by relatively low diversity across sampling sites. This phenomenon is thought to be a natural consequence of the reconstruction activities along the river, which have deleteriously affected the ecosystem. The Yeşilırmak estuary has a more diverse macrobenthic community and appeared to be better preserved than the Kızılırmak area.

关键词： HLA   NAT2   Tuberculosis   adverse drug reaction   genetic polymorphisms   isoniazid   pharmacogenomics   rifampicin  

摘要： Tuberculosis is the leading cause of death from a single infectious agent globally, with the highest burden in low-and middle-income countries. Successful treatment requires prolonged administration of multiple drugs. The increasing threat of multidrug-resistant tuberculosis has prompted the development of a robust pipeline for new drugs. While generally safe and well tolerated, adverse drug reactions (ADRs) to TB drugs have a considerable impact on treatment outcomes. Pharmacogenetic testing has been implemented for some diseases to identify at-risk individuals and prevent ADRs. For tuberculosis treatment, the use of pharmacogenetic testing to optimize complex regimens and avoid ADRs is appealing, but there has been minimal implementation. To improve the use of pharmacogenetics, understanding both the pharmacology of relevant drugs and population-specific pathophysiology of ADRs are essential. This review highlights the major treatment-limiting ADRs with TB drugs, the current understanding of drug metabolic pathways, ADR pathophysiology, and known pharmacogenetic risk alleles. We highlight research gaps and barriers to meaningful clinical use and implementation of pharmacogenomic testing to prevent adverse reactions to TB drugs.

关键词： RNA sequencing   Alleles   Gene expression   Transcriptome analysis   Genomics   RNA editing   Genetics of disease   Human genetics  

摘要： Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder with a complex genetic and molecular basis. To advance its characterization, we applied InterOmics, a novel bioinformatics pipeline integrating whole exome sequencing (WES) and RNA sequencing (RNA-seq), to saliva and skin biopsy samples from six HS patients. This approach enabled a comprehensive multiomics investigation, identifying disease-associated genetic variants and transcriptomic alterations. A key innovation of InterOmics is the Multiomics Variant Category, which classifies variants based on DNA and RNA data, capturing regulatory mechanisms such as allele-specific expression, RNA editing, nonsense-mediated decay, and gain-of-function mutations. Our findings highlight HLA gene variants and keratin-related mutations as potential contributors to HS pathogenesis. By bridging genomic and transcriptomic data, InterOmics enhances variant interpretation. This study underscores the power of multiomics-driven approaches in deciphering complex diseases, paving the way for precision medicine in HS.

关键词： 复发性流产   寿胎丸   血管内皮生长因子   可溶性血管内皮生长因子受体-1   白细胞介素17  

摘要： 目的：研究寿胎丸加味辅助治疗复发性流产患者效果及对血清血管内皮生长因子（vascular endothelial growth factor，VEGF）、可溶性血管内皮生长因子受体-1（soluble fms-like tyrosine kianse-1，sFLT-1）、白细胞介素17(interleukin-17， IL-17)的影响。方法：选取2023年1月～2024年3月医院治疗的复发性流产患者96例，按照随机数字表法均分为两组，各48例患者。对照组采用常规西药治疗，观察组在对照组基础上增加寿胎丸加味辅助治疗，用药至孕12周。比较两组患者的疗效，中医证候积分变化，血清VEGF、sFLT-1、IL-17水平，不良反应发生情况。结果：观察组治愈率87.50%、对照组70.83%，观察组高于对照组（P＜0.05）。治疗后，两组患者神疲肢软、肢体寒冷、头晕耳鸣、夜尿频繁积分均显著降低，观察组低于对照组（P＜0.05）。治疗后，两组患者血清VEGF水平明显降低，sFLT-1、IL-17水平明显升高，观察组患者血清VEGF水平高于对照组，sFLT-1、IL-17水平低于对照组，差异有统计学意义（P＜0.05）。两组均无严重不良反应发生。结论：寿胎丸加味辅助治疗复发性流产患者效果满意，能够有效调控血清内炎症因子与血管内皮相关因子，促进患者的症状缓解，保证妊娠安全。

摘要： Neoadjuvant immunotherapy is a first-line treatment for recurrent and metastatic head and neck squamous cell carcinoma. However, only a fraction of advanced HNSCC patients benefit from immunotherapy. Identifying accurate and accessible biomarkers is essential for optimal patient selection. Herein, we integrated single-cell RNA-sequencing and T cell receptor-sequencing to comprehensively characterize the tumor immune microenvironment (TIME) of HNSCC biopsies prior to a phase II neoadjuvant immunotherapy clinical trial. Tumor-specific MHC-II (tsMHC-II) was identified as a superior predictor of response to neoadjuvant immunotherapy in HNSCC compared to PD-L1. Mechanistically, tsMHC-II ignited a hot TIME and enhanced the effect of PD-1 blockade by recruiting T cells through the induction of chemokines, particularly CCL5. Moreover, tsMHC-II triggered a Th1 response and activated CD4+ and CD8+ T cell expansion, suppressing HNSCC growth in a CD4+ T-cell-dependent manner. Simultaneously, tsMHC-II facilitated an increase in PD-1+CD4+ T cells and a modest elevation in tumor PD-L1, thereby enhancing sensitivity to anti-PD-1 therapy. This study highlights that tsMHC-II, by generating an inflamed TIME, is crucial in enhancing the effectiveness of neoadjuvant immunotherapy in HNSCC.

关键词： HLA-DPA1   Idiopathic pulmonary hypertension   Mendelian randomization   Non-classical monocytes   scRNA-seq  

摘要： Aberrant immune and inflammatory responses are critical in idiopathic pulmonary arterial hypertension (IPAH). Thus, investigating immune-related therapeutic targets of IPAH is imperative. By integrating single-cell RNA sequencing (scRNA-seq), genome-wide association studies (GWAS), expression quantitative trait loci (eQTL), and single-cell eQTL (sc-eQTL) data, we identified a non-classical monocyte (NCM)-specific gene that was causally linked to PAH. NCM were classified into three subgroups based on HLA-DPA1 expression: negative, low, and high expression groups. We analyzed intercellular communication, molecular mechanisms, biological processes and assessed the metabolic activity of three subgroups. Additionally, we obtained bulk RNA-seq from lung tissue and Peripheral blood mononuclear cells (PBMCs) transcriptional profiles of IPAH patients to explore HLA-DPA1's functions. We demonstrated that IPAH patients had higher proportions of monocytes and NCM in peripheral blood compared to healthy controls. rs13203715 was causally associated with PAH and downregulated HLA-DPA1 expression in NCM. Differentially expressed genes in three subpopulations were enriched in immune and inflammatory responses. Additionally, HLA-DPA1 expression correlated with immune and inflammatory disruptions in IPAH. HLA-DPA1 exhibited significant downregulation and loss in the NCM of IPAH patients, which was closely associated with disease exacerbation by promoting immune dysregulation and vascular remodeling.