ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons.

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

Objective:To observe the effects of early energy intake and early enteral nutrition on prognosis of patients during extracorporeal membrane oxygenation (ECMO).Methods:Patients who received ECMO treatment in the emergency intensive care unit (EICU) of the Jiangsu Provincial Hospital (First Affiliated Hospital of Nanjing Medical University) from January 2021 to June 2022 were selected as subjects to summarize the early energy intake of ECMO patients. Logistic regression analysis and restricted cubic spline (RCS) analysis were used to determine the relationship between early energy intake and prognosis of ECMO patients. According to the results of RCS analysis, the patients were divided into energy-deficient group and energy-sufficient group. And according to whether early enteral nutrition (EEN) was initiated, the patients were divided into EEN group and non-EEN group. The differences of clinical outcomes between energy-deficient group and energy-sufficient group, EEN group and non-EEN group were compared.Results:There was no significant difference in age, sex, BMI, primary disease and ECMO pattern between energy-deficient group and energy-sufficient group, EEN group and non-EEN group. The ECMO conversion time (days) and hospitalization time (days) in the energy-deficient group were significantly lower than those in the energy-sufficient group, and the survival rate in the energy-deficient group was significantly lower than that in the energy-sufficient group [43.2% (19/44) vs. 66.0% (31/47), P=0.029]. Kaplan-Meier survival analysis showed that the 28-day survival rate in the energy-deficient group was significantly lower than that in the energy-sufficient group, and the risk of death was 2.595 times higher than that in the energy-sufficient group. The conversion time (days), hospital stay (days) and average daily energy intake [kcal/(kg·d)] in the EEN group were higher than those in the non-EEN group ( P<0.05), and the survival rate in the non-EEN group was significantly higher than that in the non-EEN group [66.1% (41/62) vs. 31.0% (9/29), P<0.002]. Kaplan-Meier survival analysis showed that the 28-day survival rate in the non-EEN group was significantly lower than that in the EEN group, and the risk of death was 2.981 times higher than that in the EEN group ( P<0.001). Conclusions:The energy intake of patients with ECMO above 16.94 kcal/ (kg·d) is a protective factor for prognosis. EEN helps to increase early energy intake and improve prognosis in patients during ECMO.

Objective To observe the clinical efficacy and safety of tirofiban in stent-assisted coil(SAC)embolization for patients with acutely ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured wide-necked intracranial aneurysms who underwent SAC embolization were divided into the control group and the treatment group according to cohort method.The control group was treated with aspirin enteric-coated tablets(300 mg,qd)and clopidogrel bisulfate tablets(300 mg,qd,oral administration)at 2 h before surgery.The treatment group was treated with tirofiban hydrochloride and sodium chloride injection at 10 μg·kg-1 during surgery,which was administrated via intravenous injection at a constant speed within 10 min.Then,the injection rate was adjusted to 0.1 μg·kg-1·min-1 for 12-24 h.The two groups were compared on clinical efficacy,platelet activation function[platelet alpha granule membrane glucoprotein(CD62p)positive rate,platelet adhesion rate and platelet aggregation rate],and perioperative complications.The patients were followed up for 6 months after surgery.The Glasgow Outcome Scale(GOS)scores,recurrence rate and safety were recorded.Results Fifty-three cases and forty-seven cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates of embolization in the treatment group and the control group were 91.49％(43 cases/47 cases)and 81.13％(43 cases/53 cases),without statistically significant difference(P＞0.05).On day 7 after surgery,CD62p positive rates were(56.31±7.41)％and(60.71±7.38)％;platelet adhesion rates were(37.56±3.64)％and(38.04±3.89)％;platelet aggregation rates were(27.03±3.39)％and(30.19±3.63)％.The differences in above indicators between the treatment group and the control group were statistically significant(all P＜0.05).During 6 months of follow-up,the good prognosis rates in the treatment group and the control group were 89.36％and 81.13％;recurrence rates were 4.26％and 9.43％.There were not statistically significant differences in above indicators between the treatment group and the control group(all P＞0.05).The perioperative complications in the two groups mainly included rerupture and bleeding of arterial aneurysms,subdermal ecchymosis,gingival bleeding,thrombotic events,etc.The total incidences of complications in the treatment group and the control group were 10.64％and 28.30％,with statistically significant difference(P＜0.05).Conclusion Tirofiban hydrochloride and sodium chloride injection can effectively reduce the incidence of thrombotic events in patients with acutely ruptured wide-necked intracranial aneurysms during perioperative period of SC A embolization,and improve platelet activation function.

Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Objective To design a low-code platform for data services to reduce the data interface service development costs and improve the development efficiency.Methods The platform was developed with Browser/Server(B/S)architecture,which used JAVA Spring Boot as its main framework and MySQL as the backend database system and had the functions for data source management,service catalog management,service management,service testing,service release management and service subscription management.Results The platform decreased the costs for interface development,operation and maintenance,lowered the technical threshold of interface development,unified the interface standard and enhanced hospital data security.Conclusion The platform developed provides support for hospital data interface service,digitalization and data services.[Chinese Medical Equipment Journal,2024,45(4):13-19]

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective:To compare the efficacy of reduction and in situ intervertebral fusion fixation in the treatment of degenerative lumbar spondylolisthesis.Methods:A total of 182 patients (92 males and 90 females) with L 4 degenerative lumbar spondylolisthesis of Meyerding's classification of grade I and grade II, aged (62.6±6.8) years (range, 57-73 years), who underwent posterior L 4, 5 internal fixation and interbody fusion in the Department of Spinal Surgery, the Second Hospital of Shanxi Medical University, were retrospectively analyzed from January 2019 to December 2022. There were 105 cases of I-degree spondylolisthesis and 77 cases of II-degree spondylolisthesis. According to the operation method, the patients were divided into reduction intervertebral fusion fixation (reduction group) and in situ intervertebral fusion fixation group (in situ group). Imaging parameters such as lumber lordosis (LL), pelvic incidence (PI)-LL, L 3, 4 intervertebral space heights, fusion segment angle, and sagittal vertical axis (SVA) were measured on the pre- and post-surgical lumbar spine lateral radiographs. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) of low back pain were recorded before and after surgery. The differences in clinical and imaging parameters were compared between reduction and in situ fusion group. Results:All 182 patients successfully completed the surgery and were followed up for 12.0±2.4 months (range, 9-15 months). The LL of the reduction group before surgery, immediately after surgery, and at the last follow-up were 46.9°±7.1°, 57.2°±5.9°, 55.6°±5.5°, respectively, with statistically significant differences ( F=87.61, P<0.001), with immediate and final follow-up being smaller than those in the in situ fixation group. The LL of the in situ fixation group before surgery, immediately after surgery, and at the last follow-up were 47.8°±7.2°, 50.5°±7.0°, and 48.7°± 6.4°, respectively, with no statistically significant difference ( F=2.83, P=0.062). The immediate and final follow-up of LL in the reduction group was lower than those in the in situ fixation group ( P<0.05). The fusion segment angles of the reduction group before surgery, immediately after surgery, and at the last follow-up were 14.2°±5.1°, 23.2°±4.7°, 23.2°±4.7°, respectively, with statistically significant differences ( F=152.87, P<0.001), with immediate and final follow-up after surgery being greater than before surgery. The fusion segment angles of the in situ fixation group before surgery, immediately after surgery, and at the last follow-up were 15.4°±5.9°, 18.2°±5.5°, and 17.4°±5.1°, respectively, with statistically significant differences ( F=4.69, P=0.009), with immediate and final follow-up being greater than before surgery. The fusion segment angulation in the reduction group was greater than that in the in situ fixation group at both the immediate and final follow-up ( P<0.05). The SVA of the reduction group before surgery, immediately after surgery, and at the last follow-up were 16.9±18.2 mm, 9.5±12.0 mm, and 8.7±11.3 mm, respectively, with statistically significant differences ( F=11.32, P<0.001), with immediate and final follow-up being smaller than before surgery. The SVA of immediately after surgery and at the last follow-up were both smaller than before surgery. The SVA of the in situ fixation group before surgery, immediately after surgery, and at the last follow-up were 16.4±17.2 mm, 14.3±15.5 mm, and 13.8±15.0 mm, respectively, with no statistically significant difference ( F=0.57, P=0.576). The SVA of the reduction group at immediate and final follow-up was lower than that of the in situ fixation group ( P<0.05). Conclusion:Both reduction and in situ intervertebral fusion fixation can effectively relieve the clinical symptoms of patients. Fusion fixation after reduction can improve the angulation of fusion segments to form segmental kyphosis, which is more conducive to improving SVA.