Objective To analyze the epidemiological characteristics of norovirus outbreaks in Haidian District, Beijing, and to provide a reference for epidemic prevention and control. Methods Descriptive epidemiological methods were used to organize and statistically analyze the norovirus outbreak data reported from 2016 to 2022. Results A total of 26 outbreaks of norovirus were reported in Haidian District, with a total of 1595 cases and an attack rate M (Q_R) of 8.23 (16.33)%. There were 24 cases of norovirus type GII (92.31%), 1 case of type GI (3.85%), and 1 case of mixed infection of virus type GI/GII (3.85%). The highest number of reported outbreaks occurred in March and April, with 17 cases, accounting for 65.38%. The highest number of reported cases was in November and December, with 785 cases, accounting for 44.92%. The case age M (Q_R) was 18 (14) years old. The detection rate of positive samples in different age groups had statistical significance（χ²=12.021, P=0.007). The 26 outbreaks were mainly distributed in collective units such as schools, preschool institutions, and enterprises and institutions. There were a total of 11 outbreaks related to foodborne transmission, with 923 cases, accounting for 57.87%. Diarrhea was positively correlated with the age of the cases (r_s=0.572, P<0.001), while vomiting was negatively correlated with the age of the cases (r_s=-0187, P<0.001). The time interval between the onset of acute gastroenteritis symptoms in the first case and the reporting of the epidemic was positively correlated with the duration of the epidemic (r_s=0.586, P=0.002). Conclusion It is necessary to strengthen the prevention and control of norovirus in schools (primary and secondary schools and colleges), strictly implement health monitoring and regular screening for kitchen workers, carry out publicity and education, detect cases as early as possible, report the epidemic in a timely manner, and effectively reduce the scale of the epidemic and prevent its spread.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective : To investigate the effects of resveratrol(Res) on fibroblast-like synoviocytes(FLS) in patients with rheumatoid arthritis(RA), and to explore the possible mechanism of Res inhibiting the release of inflammatory factors from FLS. Methods : FLS from RA patients were culturedin vitroand treated with different concentrations of Res(0, 20, 40, 80, 160, 320 μmol/L). The viability of FLS cells was detected by CCK-8 assay after 12 and 24 h. The contents of inflammatory factor interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatant were detected by ELISA. The expression levels of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS) and stimulator of interferon gene(STING) were measured by Western blot; After lentivirus infection with FLS caused the cells to overexpress cGAS, the cells were divided into Control group(blank control), cGAS group(cGAS overexpression), Res+cGAS group(Res 160 μmol/L+cGAS overexpression) and Res group(Res 160 μmol/L). The expression level of STING protein in cells of each group was determined by Western blot, the viability of FLS cells in each group was detected by CCK-8, and the contents of inflammatory factor IL-6 and TNF-α in the supernatant of cells of each group were detected by ELISA method. Results : The results of CCK-8 experiment showed that under 40, 80, 160 μmol/L Res treatment, FLS viability decreased significantly after 24 h compared with blank control group(P<0.01). ELISA results showed that the contents of IL-6 and TNF-α in cell supernatant were also significantly decreased after treatment with Res of 40, 80 and 160 μmol/L(P<0.01). Meanwhile, Western blot results showed that Res could significantly decrease the protein expression levels of STING and cGAS in FLS cells after treatment of 40, 80 and 160 μmol/L(P<0.05,P<0.01). Compared with the Control group, the expression level of STING protein in FLS increased after overexpression of cGAS(P<0.05); compared with the Res group, the content of inflammatory factors in the supernatant of FLS and the expression level of STING protein in FLS significantly increased after overexpression of cGAS(P<0.01,P<0.05). Conclusion The appropriate concentration of Res can inhibit the release of inflammatory cytokines in FLS cells, which may be related to the blocking of cGAS-STING signaling pathway.

Objective: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. Methods: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated. Results: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. Conclusion NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Purpose: This study aimed to evaluate the long-term efficacy of the ligation of the intersphincteric fistula tract (LIFT) procedure in treating high transsphincteric fistulas. Methods: We conducted a retrospective study to evaluate the success rate of LIFT treatment in 82 patients with high transsphincteric fistulas involving at least one-third of the external sphincter. This study was carried out across 2 centers from November 2009 to February 2023. Results: All patients underwent successful surgery with a median operative time of 48.9 minutes (range, 20–80 minutes), and no intraoperative or postoperative complications were reported. The median follow-up duration was 85.5 months (range, 4–120 months), with 5 patients (6.1%) lost to follow-up. Treatment was successful in 62 patients, whose symptoms disappeared and both the external opening and the intersphincteric incision completely healed, yielding an overall efficiency rate of 80.5%. There were 15 cases (19.5%) of treatment failure, including 6 (7.8%) that converted to intersphincteric anal fistula and 9 (11.7%) that experienced persistent or recurrent fistulas. Only 1 patient reported minor overflow during the postoperative follow-up, but no other patients reported any significant discomfort. There were no statistically significant differences between patients with surgical success and those with treatment failure in terms of fistula length, history of previous abscess or anal fistula surgery, number of external orifices or fistulas, and location of fistulas (all P>0.05). Conclusion LIFT is a safe and effective sphincter-preserving procedure that yields satisfactory healing outcomes and has minimal impact on anal function.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.