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: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells （KGN cells） in polycystic ovarian syndrome （PCOS） and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52， 1.04， 2.08 g/（kg·d）] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum， KGN cells were divided into control group （without any treatment）， dehydroepiandrosterone （DHEA） group （treated with 50 μmol/L DHEA for 48 h）， blank serum group （treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h） and medium-concentration of Siwutang medicated serum group （treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h）. The number of autophagosomes was observed in each group， and protein expressions of pathway-related proteins [fructose-1， 6-bisphosphatase 1 （FBP1），mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）]， autophagy-related proteins [p62， microtubule-associated protein 1 light chain 3 （LC3）] and mRNA expression of FBP1 were also detected. The （transfected） cells were further divided into Siwutang group （treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA）， Siwutang+si-NC group [negative control small interfering RNA （siRNA） transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group （FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration Siwutang medicated serum for 72 h）. The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group， DHEA group exhibited an increase in the number of autophagosomes， an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR， as well as increases in protein and mRNA expressions of FBP1， and decreased protein expression of p62 （P＜0.05）. Compared to both DHEA group and blank serum group， the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes， a decrease in LC3-Ⅱ/LC3-Ⅰ， and increases in p-mTOR/mTOR， protein expression of p62， protein and mRNA expressions of FBP1 （P＜0.05）. After knocking down FBP1， compared with Siwutang+si-NC group， Siwutang+si-FBP1 group showed a significant decrease in cell viability， protein expression of p62 ， protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR， and an increase in LC3-Ⅱ/LC3-Ⅰ （P＜0.05）. CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells， thus inhibiting autophagy of KGN cells.

OBJECTIVE To provide reference for the establishment and improvement of the regulatory system of patients’ medicine instructions in China. METHODS Through searching the official website of the European Medicines Agency （EMA） and related literature， the definition， basic nature， and content of patients’ medicine instructions in the European Union were introduced， and the characteristics of the management system of patients’ medicine instructions in the European Union were analyzed in terms of the management department， approval and change procedures， readability requirements and information accessibility requirements. At the same time， the pilot situation of patients’ medicine instructions in China， as well as problems in the paths of classification and management， readability of content， and information timeliness were analyzed to put forward suggestions. RESULTS & CONCLUSIONS European Union had a dedicated department for the management of medicine instructions； the approval and change procedures for patients’ medicine instructions were clear， the readability requirements were detailed， the readability verification program with patient participation was established， and multi-channel and timely information disclosure was adopted. It is recommended that China establish a mechanism to categorize and manage professionals’ and patients’ medicine instructions， guide multiple parties to participate in the design of patients’ medicine instructions and refine the readability requirements， and improve the mechanism for disclosure of medicine instructions to enhance the timeliness of medication information.

OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells （KGN cells） in polycystic ovarian syndrome （PCOS） and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52， 1.04， 2.08 g/（kg·d）] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum， KGN cells were divided into control group （without any treatment）， dehydroepiandrosterone （DHEA） group （treated with 50 μmol/L DHEA for 48 h）， blank serum group （treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h） and medium-concentration of Siwutang medicated serum group （treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h）. The number of autophagosomes was observed in each group， and protein expressions of pathway-related proteins [fructose-1， 6-bisphosphatase 1 （FBP1），mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）]， autophagy-related proteins [p62， microtubule-associated protein 1 light chain 3 （LC3）] and mRNA expression of FBP1 were also detected. The （transfected） cells were further divided into Siwutang group （treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA）， Siwutang+si-NC group [negative control small interfering RNA （siRNA） transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group （FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration Siwutang medicated serum for 72 h）. The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group， DHEA group exhibited an increase in the number of autophagosomes， an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR， as well as increases in protein and mRNA expressions of FBP1， and decreased protein expression of p62 （P＜0.05）. Compared to both DHEA group and blank serum group， the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes， a decrease in LC3-Ⅱ/LC3-Ⅰ， and increases in p-mTOR/mTOR， protein expression of p62， protein and mRNA expressions of FBP1 （P＜0.05）. After knocking down FBP1， compared with Siwutang+si-NC group， Siwutang+si-FBP1 group showed a significant decrease in cell viability， protein expression of p62 ， protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR， and an increase in LC3-Ⅱ/LC3-Ⅰ （P＜0.05）. CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells， thus inhibiting autophagy of KGN cells.

Objective: To investigate the intentions of mothers of ageappropriate girls in Qingdao to vaccinate their daughters against human papillomavirus (HPV), so as to provide theoretical guidance for targeted health education in the future. Methods: A multistage random sampling method was adopted to conduct a crosssectional study among 2 244 mothers of girls aged 12-14 years in Qingdao from March to December 2023. The Mann-Whitney U test was used for group comparisons, and Logistic regression was performed to analyze the factors that influenced maternal intention to vaccinate their ageappropriate daughters against HPV. Results: Among the surveyed mothers, 89.22% (n=2 002) intended to vaccinate their daughters against HPV, and 68.58% (n=1 539) had fully vaccinated or had plans to complete it for themselves. The knowledge score of mothers intended to vaccinate their daughters was 10 (8, 11). The multivariate Logistic regression analysis showed that mothers aged >45 years (OR=0.19), those with an annual family income of 60 000-<150 000 yuan (OR=0.65), 150 000-<300 000 yuan (OR=0.58), 300 000-500 000 yuan (OR=0.22), and those with higher knowledge scores (OR=0.90) were more likely to vaccinate their daughters (P<0.05). Mothers with a junior college or undergraduate degree (OR=1.66), those who never or occasionally screened for HPV (OR=1.58), those who were intended to be vaccinated, not planning to complete the fullcourse vaccination, or overaged and unvaccinated (OR=7.13), those who were not concerned about their daughters HPV infection (OR=2.54), and those whose daughters were not in adolescence (OR=1.93) were less intended to vaccinate their daughters (P<0.05). The primary reasons for vaccine hesitancy were vaccine safety concerns (65.06%), followed by the belief of mothers that "the children is to young, and can be vaccinated when they are older" (13.25%). Conclusions Mothers of eligible girls in Qingdao have relatively higher intentions to vaccinate their daughters against HPV, and willingness is influenced by factors such as the mothers vaccination status, knowledge level, and daughters development stage. It is recommended to strengthen targeted health education, improve the cognitive level and acceptance of mother, and increase the vaccination rate of HPV vaccines.

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.