Objective To investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. Results IVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. Conclusion Actinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.

Objective To analyze the influenza-like illness (ILI) data in Ordos City from 2017 to 2023 and conduct nucleic acid detection of the virus to understand the local influenza epidemic situation, and to provide a reliable basis for influenza prevention and control in the city. Methods Real-time quantitative polymerase chain reaction (qPCR) was used to identify virus subtypes in ILI throat swab samples. Comparisons of positive rates were conducted using the chi-square test, with a significance level of α=0.05. Results From 2017 to 2023, a total of 3,283,434 outpatient and emergency visits were recorded at the Ordos City Central Hospital, including 74,159 ILI cases, with an ILI proportion of 2.26%. The majority of ILI cases (74.43%) occurred in children aged 0~14 years old. The overall positive rate of influenza virus nucleic acid detection was 10.87%, with the highest proportion being subtype A (seasonal H3) at 43.03%. The highest detection rate was observed in the 5~14 years age group, with statistically significant differences in positive rates across age groups (χ²=155.638, P<0.001). Influenza peaks occurred mainly from November to March of the following year. From January to April, three types of influenza were prevalent alternately or mixed, while from October to December, subtype A (seasonal H3) predominated. Positive rates varied significantly across months (χ²=250.923, P<0.001). The temporal trends of ILI proportions and PCR-positive rates were consistent. Conclusion Influenza in Ordos City exhibits distinct seasonal and age distribution characteristics, with alternating or mixed circulation of three virus types. Continued efforts are needed to strengthen influenza surveillance, especially the prevention and control of influenza in infants and adolescents.

AIM: To investigate and analyze serum nitric oxide synthase 4(NOX4)and matrix metalloproteinase(MMP)-2 expressions in patients with diabetes mellitus(DM)complicated with neovascular glaucoma(NVG)and their clinical significance.METHODS: A prospective study was conducted on 161 patients with DM complicated with NVG admitted to Handan City Eye Hospital(The Third Hospital of Handan)from June 2020 to June 2023. Based on whether complications occurred 1 a after trabeculectomy in the study group patients, they were divided into a group with good prognosis(n=90)and a group with poor prognosis(n=71). During the same period, 161 patients with chronic angle-closure glaucoma without iris neovascularization were selected as the control group. ELISA method was applied to detect the expression levels of serum NOX4 and MMP-2. ROC curve was plotted to evaluate the diagnostic value and postoperative complication prediction value of NOX4 and MMP-2 in patients with DM complicated with NVG. Pearson method was applied to analyze the correlation of NOX4 and MMP-2 with vascular endothelial growth factor(VEGF)and interleukin-6(IL-6). Multivariate Logistic regression was applied to analyze the influencing factors of postoperative complications in the study group.RESULTS:The general information of the study group and control group of patients is comparable. Compared with the control group, the expression levels of serum NOX4, MMP-2, VEGF, and IL-6 in the study group were significantly increased(P<0.001). According to Pearson analysis, serum NOX4 and MMP-2 levels significantly positively correlated with VEGF and IL-6 levels, respectively(P<0.001). According to ROC curve, the AUC of NOX4 combined with MMP-2 in the diagnosis of DM complicated with NVG was better than that of individual diagnosis of NOX4(Z=3.341, P<0.05)and MMP-2(Z=2.788, P<0.05). The duration of DM, the proportion of people with intraocular pressure >21 mmHg, and the expression levels of NOX4, MMP-2, VEGF, and IL-6 in the poor prognosis group were all higher than those in the good prognosis group(P<0.001). The duration of DM, intraocular pressure >21 mmHg, the levels of NOX4, MMP-2, VEGF, and IL-6 were all risk factors for poor prognosis in DM patients with NVG(P<0.001). According to ROC curve, the combined prediction of NOX4 and MMP-2 for postoperative complications in patients with DM complicated by NVG was superior to the AUC predicted by NOX4(Z=3.727, P<0.05)and MMP-2(Z=2.219, P<0.05), respectively.CONCLUSION:NOX4 and MMP-2 are upregulated in the serum of patients with DM complicated by NVG. Combined detection of these two markers holds significant clinical value for the early diagnosis and prognosis of patients with DM complicated by NVG.

Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

OBJECTIVE: This study aims to address the configuration and efficiency issues in the use of digital subtraction angiography (DSA) equipment through the practical implementation of a rationalization platform based on the Internet of Things (IoT). METHODS: By employing IoT and data integration technologies, the deep integration of DSA equipment operational data with clinical data was achieved to construct a knowledge base for rational use of DSA equipment. Simultaneously, a knowledge base was developed using software engineering techniques to visually display data analysis results. RESULTS: Through thorough data analysis, an imbalance in DSA usage between the southern and northern hospital campuses was identified. Addressing this issue, optimizations were implemented based on the data analysis results, which ultimately yielded significant effects. These adjustments not only effectively alleviated the pressure on DSA equipment usage in the southern campus, but also increased equipment utilization in the northern district (the average daily working hours have increased from 4.64 h to 7.19 h), shortened patient appointment wait time (the appointment duration in the southern campus decreased by 21.86% year-on-year, while the appointment duration in the northern campus decreased by 20.51% year-on-year). CONCLUSION Through the practical implementation of a DSA rationalization platform based on IoT, this study not only successfully explored methods for rational DSA usage but also provided valuable reference for the rational management of medical equipment.
Internet of Things ; Angiography, Digital Subtraction/instrumentation* ; Humans ; Software

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) originator and biosimilars in the treatment of Crohn′s disease (CD).Methods:From January 2020 to January 2023, the clinical data of 73 patients who were diagnosed as CD and received ADA treatment at the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University were retrospectively analyzed. Among them, 30 patients received ADA originator treatment (National Medicine Approval Number SJ20181019; originator group), 23 patients received biosimilar A treatment (Medicine Medicine Approval Number S20190038; biosimilar A group), and 20 patients received biosimilar B (Medicine Medicine Approval Number S20190043; biosimilar B group). At 12 and 48 weeks after treatment, the clinical data of clinical remission (Crohn′s disease activity index(CDAI) score <150), clinical response (CDAI score decreased ≥ 70 from baseline), endoscopic remission (simple endoscopic score for Crohn′s disease (SES-CD) ≤ 2 or Rutgeerts score ≤ 1), endoscopic response (SES-CD decreased > 50% from baseline), and adverse drug reaction (ADR) were collected. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:After 12 weeks of ADA treatment, the overall clinical remission rate was 69.9% (51/73), which of the biosimilar A group was 69.6% (16/23), the biosimilar B group was 75.0% (15/20), and the originator group was 66.7% (20/30). The overall clinical response rate was 83.6% (61/73), which of the biosimilar A group was 82.6% (19/23), the biosimilar B group was 80.0% (16/20), and the originator group was 86.7% (26/30). The overall endoscopic remission rate was 42.5% (31/73), which of the biosimilar A group was 52.2% (12/23), the biosimilar B group was 45.0% (9/20), and the originator group was 33.3% (10/30). The overall endoscopic response rate was 63.0% (46/73), which of the biosimilar A group was 73.9% (17/23), the biosimilar B group was 70.0% (14/20), and the originator group was 50.0% (15/30). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). After 48 weeks of treatment, the overall clinical remission rate was 54.2% (32/59), which of the biosimilar A group was 8/18, the biosimilar B group was 9/15, and the originator group was 57.7% (15/26). The overall clinical response rate was 71.2% (42/59), which of the biosimilar A group was 10/18, the biosimilar B group was 12/15, and the originator group was 76.9% (20/26). The overall endoscopic remission rate was 25.4% (15/59), which of the biosimilar A group was 5/18, the biosimilar B group was 3/15, and the originator group was 26.9% (7/26). The overall endoscopic response rate was 40.7% (24/59), which of the biosimilar A group was 7/18, the biosimilar B group was 5/15, and the originator group was 46.2% (12/26). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). The overall incidence of ADR was 32.9% (24/73), which of the biosimilar A group was 30.4% (7/23), the biosimilar B group was 30.0% (6/20), and the originator group was 36.7% (11/30); and there was no statistically significant difference among the 3 groups ( P=0.847). Conclusion:ADA biosimilars A and B demonstrate comparable efficacy and safety to the originator medication in the treatment of CD.

Objective To understand the implementation of WS/T 508-2016 and the status of washing and disin-fection of medical textiles in China,and provide basis for the revision of the standard.Methods A questionnaire survey was conducted on the management of medical institutions and washing and disinfection workplace,building layout,personnel protection,equipment and supplies,washing and disinfection principles,and hygiene quality mo-nitoring of medical textiles in 323 medical institutions and 31 washing institutions in China.Meanwhile,microbio-logical index sampling was conducted on 234 pieces of medical textiles in 9 medical institutions and 8 washing insti-tutions in Hubei,Shanxi,Shanghai,and Sichuan Provinces before and after washing and disinfection.Results The awareness rates of WS/T 508-2016 among medical institutions and washing institutions were 96.90％and 96.77％,respectively,and the implementation rates were 94.12％and 96.77％,respectively.47.99％medical in-stitutions use purchasing services for washing and disinfecting medical textiles,and the higher the level of the medi-cal institution was,the higher the proportion of purchasing services was(x2=15.312,P＜0.001).85.16％medi-cal institutions have conducted risk assessments on service providers,and 52.99％were responsible for or participa-ted in pre-job training by the medical institution.Washing institutions were higher than medical institutions in terms of system soundness rate,pre-job training rate,proportion of quality management leaders and full-time(part-time)quality inspectors,setting rate of hand-washing facilities in zones,passages,isolation barriers,dressing(buffer)room,and toilets,configuration rate of hygiene isolation washing equipment,tunnel washing unit,washing equip-ment with heating functions,drying equipment and mechanical ventilation facilities,and specialty machine washing rate.Among 234 medical textiles specimens,11.97％were detected fungi,and the total fungal colonies in 5 clean textiles exceeded 100 CFU/100 cm2.Conclusion WS/T 508-2016 can further standardize the washing and disin-fection of medical textiles in China through strengthening institutional management,improving the supervision level of service providers,perfecting hardware facilities and layout,introducing new technologies,and increasing the mo-nitoring on fungi in clean textiles.

Objective:To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.Methods:A retrospective study was conducted on 7 patients diagnosed by Yangjiang People′s Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People′s Hospital of Yangjiang (Ethics No: 20240001).Results:For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A 2, whilst another had significantly decreased Hb A and Hb A 2, in addition with the appearance of a Hb H band. The content of Hb Bart′s in four neonates was ≥0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c. 2delT, HBA2: c. 1A>G, HBA2: c. 1A>T, and HBA1: c. 2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c. 427T>C (Hb CS) and HBA2: c. 2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c. 1A>G and Southeast Asian type deletion. Conclusion:Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c. 1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.