Objective: To understand the epidemiological and etiological characteristics of food poisoning event occurred in a school in Hangzhou, Zhejiang, so as to provide reference for the scientific management of related emergencies. Methods: By determining the nature of the event through epidemiological investigation, a case control study was carried out to spot suspicious food in May 2024. The hygienic investigation was conducted to find out possible pollution links and factors, patients and canteen practitioners anal swab, canteen retention samples, catering link daub and other specimens were collected ,for rapid pathogen screening. And the suspected pathogen Clostridium perfringens (CP) were isolated and identified according to the screening results, and toxin gene detection and whole genome sequencing and cluster analysis of CP isolated strains were carried out. Results: The incident resulted in 45 people experiencing gastrointestinal symptoms, such as diarrhea and abdominal pain. The suspicious food was tomato scrambled eggs and corn ribs provided by the student canteen for lunch on May 29. A hygiene investigation found that there was a risk of contamination in the food processing, preparation and storage. A total of 46 anal swabs and 10 canteen retention samples were positive for CP 16 S, 59 strains of CP were isolated from 27 samples, 10 cases and 1 practitioner isolate were positive for CPE ( cpe ) (F mode), and their whole genome evolution analysis was conducted based on the same source. Conclusions The food poisoning event is caused by CP infection carrying CPE ( cpe ) (F mode), and the possible sources of outbreak are the carriers of the CP by employees. It is recommended that cafeteria staff strengthen training on common foodborne diseases and conduct regular monitoring of pathogens.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Molecular editing around privileged scaffolds, also known as periphery editing, is a commonly used strategy in contemporary drug discovery and development. Tranylcypromine (TCP) is a widely acknowledged scaffold with diverse pharmacological activities. TCP-derived compounds target different enzymes and cellular receptors such as amine oxidase, platelet P2Y₁₂ receptor, and cytochrome P450 superfamily. These compounds have demonstrated various effects including antidepressant, anticancer, antiviral properties, involvement in prostaglandin synthesis, and mediation of drug metabolism. Notably, the first reversible oral P2Y₁₂ receptor antagonist, ticagrelor, is currently used to prevent future myocardial infarction, stroke, and cardiovascular death. Several TCP-based lysine demethylase 1 (LSD1) inhibitors are currently undergoing clinical assessment. MIV-150, a third-generation non-nucleoside reverse transcriptase inhibitor, has progressed to the clinical stage for treating human immunodeficiency virus type 1 (HIV-1) seronegative patients suffering from acute coronary syndrome. This review aims to explore the target landscape of TCPs, highlight key structure-activity relationships (SARs), and emphasize the therapeutic potential of TCPs for treating various diseases. Finally, the lessons learned from our medicinal chemistry practice, challenges and future directions of TCP-based drug discovery are briefly discussed.

Objective: To establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. Methods: The pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. Results: We identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. Conclusion This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.

OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy （DN） model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group， aminoguanidine group （positive control，100 mg/kg） and cornuside group （100 mg/kg）， and male C57BL/6J mice were included as normal group， with 6 mice in each group. Administration groups were given relevant medicine intragastrically， and normal group and model group were given a constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The levels of fasting blood glucose （FBG）， 24 h urinary protein， serum interleukin-12 （IL-12）， IL-10， blood urea nitrogen （BUN） and serum creatinine （Scr） were detected； the pathological injury， fibrotic change and glomerular microstructure of renal tissue were observed； the expressions of the receptor of advanced glycation end products （RAGE）， collagen type Ⅳ （COL-Ⅳ） and inducible nitric oxide synthase （iNOS） in renal cortex were detected in each group. RESULTS Compared with normal group， the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes； the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits； the levels of FBG and 24 h urinary protein， the serum levels of IL- 12， BUN and Scr， and the expression levels of RAGE， COL-Ⅳ and iNOS in the renal cortex were significantly increased， while the serum level of IL-10 was significantly decreased （P＜0.01）. Compared with the model group， the renal pathological injuries， fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly， and the above quantitative indexes were generally improved （P＜0.05 or P＜0.01）. CONCLUSIONS Cornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response， reduce urinary protein excretion， and alleviate renal fibrosis， which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.

[Objective] To explore the value of the TyG index for predicting postoperative recurrence in persistent atrial fibrillation (AF) patients combined with on-alcoholic fatty liver disease (NAFLD) undergoing catheter ablation. [Methods] This study was a single-center, retrospective, cohort study. Clinical data of patients who underwent catheter ablation during hospitalization or outpatient visits at The First Affiliated Hospital of Xi’an Jiaotong University from January 2021 to December 2022 were retrospectively collected. The patients were divided into recurrence and non-recurrence groups based on whether AF recurred within 1 year after the procedure. General clinical data and relevant laboratory test results were collected, and the preoperative TyG index was calculated. The risk factors for AF recurrence after catheter ablation in these patients were analyzed using univariate and multivariate COX proportional hazards regression models. The value of the TyG index for predicting AF recurrence was assessed using receiver operating characteristic (ROC) curve analysis. [Results] We recruited 167 patients, among whom 103 were males and 64 were females. The mean follow-up time was 12±1.3 months, with 52 cases of AF recurrence and 115 ones of non-recurrence. Compared with the non-recurrence group, the TyG index was higher in the recurrence group (9.62±0.96 vs. 8.26±0.46, P<0.05). Multivariate COX regression analysis showed that the preoperative TyG index (HR=1.35, 95% CI: 1.10-1.60, P<0.05) and postoperative electrocardiogram P-wave dispersion (HR=1.51, 95% CI: 1.32-1.70, P<0.001) were risk factors for AF recurrence after catheter ablation in persistent AF patients with NAFLD. The ROC curve analysis showed that the area under the curve (AUC) for the TyG index in predicting AF recurrence after catheter ablation in these patients was 0.846 (95% CI: 0.773-0.919, P<0.001). [Conclusion] The TyG index is an effective indicator for predicting atrial fibrillation recurrence after catheter ablation in persistent AF patients combined with NAFLD.

Objective:To explore the current status of body posture health belief and knowledge mastery among Chinese adolescents.Methods:Adolescents’ body posture questionnaire was designed based on health belief model including health belief and health knowlege about body posture.The survey was conducted on 72 classes in 6 provinces using stratified cluster sampling, and 3 513 valid questionnaires were obtained.Descriptive analysis, the rank sum test, and χ2-test were used for statistical analysis by SPSS 25.0 software. Results:(1) The scores of all dimensions of body posture health belief decreased with the increase of academic stage.In participants from primary schools, middle schools and high schools, the scores of perceived susceptibility were (27.32±4.28), (26.51±4.59), and (25.87±3.68)respectively, the scores of perceived severity were(27.27±5.26), (26.30±5.44), and (25.52±4.91)respectively, the scores of perceived benefits were (21.10±2.93), (20.57±3.19), and (20.00±2.93)respectively, the scores of perceived barriers were (24.18±5.24), (23.14±5.04), and (22.63±4.51)respectively, the scores of self-efficacy were (24.64±3.19), (24.12±3.31), and (23.58±3.11) respectively, and the differences were all statistically significant among different academic stages ( H=78.27, 80.98, 71.40, 56.74, 53.73, all P<0.01).(2) Participants with better family socioeconomic status and urban participants had higher scores in perceived susceptibility, perceived severity and perceived benefits than other participants (all P<0.01).(3)In terms of knowlege mastery, the proportions of students with good, general and poor knowledge mastery were 5.5%(193/3 513), 69.5%(2 440/3 513) and 25%(880/3 513).Among urban, town and rural adolescents, the proportion of students with good knowledge mastery were 6.6%(961/1 461), 3.7%(39/1 043), and 2.7%(27/1 009), respectively, and there was a statistical difference between urban and rural areas ( χ2=36.67, P<0.01).Among adolescents with good, general and poor family socioeconomic status, the proportion of students with good knowledge mastery were 8.9%(87/974), 5.0%(80/1 595) and 2.8%(26/944), respectively ( χ2=41.79, P<0.01). Conclusion:Adolescents lack health knowledge of body posture and awareness of the related risk factors, and have difficulty in adopting health behaviors.Adolescents from high school, rural areas and families with lower socioeconomic status need more targeted spine-related health education.

Objective To analyze the clinical phenotypes and mutation types of children with X-linked Alport syndrome(XLAS)with mutations in COL4A5 gene,and to explore the relationship between children with XLAS and nephrotic syndrome nephritic type.Methods Thirty-two children with COL4A5 gene mutations detected by second-generation sequencing and finally diagnosed with Alport syndrome at Guangzhou Red Cross Hospital affiliated with Jinan University and the First People's Hospital of Guangzhou between April 2016 and April 2023 were included,and their clinicopathological features and gene mutation characteristics were retrospectively analyzed.Results The mean age of onset of disease in children with XLAS was(3.68±2.07)years old,the mean age at diagnosis(6.56±2.95)years old,12 cases(37.5%)started with isolated hematuria,8 cases(25%)started with hematuria and proteinuria,12 cases(37.5%)started with nephrotic syndrome nephritic phenotype,and the positive family history of the children was found in 11 cases(34.4%),ocular lesions were found in 3 cases(9.37%),ear lesions in 6 cases(18.75%),and 7 cases(21.87%)were found to have developed chronic kidney disease(CKD)in the later follow-up.21 children underwent renal tissue puncture biopsy,and electron microscopy showed thinning of the basement membrane(diffuse or segmental)in 13 cases(61.9%),and uneven thickness of the basement membrane in 8 cases(38.09%);light microscopy showed thinning of the basement membrane in 13 cases(61.9%);light microscopy showed thinning of the basement membrane in 8 cases(38.09%);and light microscopy showed thinning of the basement membrane in 3 cases(11.5%).(38.09%);light microscopy:focal segmental glomerulosclerosis(FSGS)in 2 cases(9.52%),mesangial proliferative glomerulonephritis(Ms PGN)in 11 cases(52.38%),and minimal change disease(MCD)in 8 cases(38.09%).The type of mutation was categorized as missense mutation in 12 cases(37.5%),shear site mutation in 9 cases(28.12%),nonsense mutation in 6 cases(18.75%),deletion mutation in 3 cases(9.37%),and code shift mutation in 2 cases(6.25%).Genetic mutations were present in 22 cases(68.75%);spontaneous mutations were present in 10 cases(27.02%).Conclusions Children with XLAS have atypical clinical manifestations and pathologic features in the early stage of the disease,and the progress is slow,and some of them are easy to be misdiagnosed as nephrotic syndrome nephritis type in the early stage,so it is important to improve the genetic test for this disease as early as possible,and to make reason-able drug choices to predict the prognosis scientifically.

ObjectiveTo describe a COVID-19 outbreak due to SARS-CoV-2 Omicron variant in a school and provide suggestions for COVID-19 prevention and control. MethodsData on the COVID-19 outbreak in a school in Putuo District of Shanghai were collected from November 14 to December 20， 2022. Epidemiological characteristics， incidence rate of secondary cases and response measures were described and analyzed. ResultsA total of 27 COVID-19 cases were identified infected with SARS-CoV-2 Omicron BA.5.2 variant， including 14 students （51.9%） and 13 family members / teachers living with those students （48.1%）. The first case occurred on November 14， with peak incidence during November 16-18. The median generation interval of the second generation cases was 2 （2，3） days. The index case （case 1， a student） had a clear contact history outside the school， which was found through routine examination in key populations in the school. Immediate management was conducted after the notification. All the second generation cases were exposed students in the same class with case 1， which were identified during the quarantine， whereas the third generation cases were their family members/teachers living with the second generation cases. The incidence rate within the class and school were 36.8% and 3.0%， respectively. No further social transmission was found outside the school. ConclusionEarly detection， multi-sectoral collaboration， prompt control and quarantine measures are effective in containing SARS-CoV-2 transmission. Health promotion， surveillance， ventilation and prophylactic disinfection should be reinforced in schools， office buildings and other gathering places.

Objective:To investigate the clinical and cardiac magnetic resonance (CMR) characteristics of heart involvement in patients with Fabry disease (AFD).Methods:From January 2018 to March 2021, eight AFD patients [3 males and 5 females, mean age (50±11) years old, range 26-60 years old] confirmed by genetic testing or pathology in Fuwai Hospital were retrospectively included in this study. At the same time, sixteen patients with hypertrophic cardiomyopathy (HCM) [6 males and 10 females, mean age (46±15) years old] and 16 healthy individuals [6 males and 10 females, mean age (51±11) years old] were included as controls. The clinical baseline data and CMR data of the patients were collected and analyzed. The CMR data were analyzed using the software CVI42, with the corresponding parameters automatically generated. One-way ANOVA or Kruskal-Wallis test was used to compare the differences in the parameters among the three groups. Independent-samples t test, Fisher precise test or Mann-Whitney U test were used for the comparison between each two groups. Results:Statistically significant difference was found in renal insufficiency between the HCM group and the AFD group; No other significant difference was found in other clinical factors and ECG results (all P>0.05). CMR results showed that in the AFD group, there were 5 cases with symmetric or roughly symmetric hypertrophy, and 3 with asymmetric hypertrophy. The late gadolinium enhancement (LGE) showed myocardial enhancement in 5 patients, mainly presenting as multiple intermural enhancement, and partially as local subendocardial enhancement. In the HCM group, fourteen cases suffered mainly asymmetric ventricular septal thickening, with or without thickening of other parts of left ventricular wall; and 2 cases had thickening of middle and distal part of the left ventricle. The LGE showed myocardial enhancement in 14 patients, which manifested as focal or patchy enhancement in hypertrophic myocardium, including focal enhancement in the right ventricular insertion of ventricular septum (more common) and subendocardial enhancement in the middle and far segments of left ventricle. Statistically significant difference was found in the differences between the left atrial anterior posterior diameter, the maximum wall thickness of left ventricular, the left ventricular myocardial mass index (LVMI) and the native T 1 value among the three groups (all P<0.001). However, there was no statistically significant difference in the left atrial anterior posterior diameter and the maximum wall thickness of left ventricular between AFD group and HCM group ( P>0.05). The LVMI in AFD group was higher than that in healthy group and HCM group (all P<0.05). Significant difference was found in the native T 1 value among the three groups, with the native T 1 value of the AFD group [(1 177.4±46.0) ms] was significantly lower than that of the healthy group [(1 244.5±34.3) ms] and the HCM group [(1 278.8±41.6) ms], with ( F=13.10, P<0.001). Conclusions:The clinical characteristics of AFD and HCM are quite similar. When AFD is suspected, CMR imaging should be the first choice for imaging examination. Especially, T 1 mapping imaging can provide important information for the diagnosis of AFD.