Dendrobii Caulis Mixture-containing Serum Protects Mice from Podocyte Injury Induced by High Glucose / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L-1 glucose+10% blank serum）， model （30 mmol·L-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L-1 glucose+10% blank serum+1 μmol·L-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe2+ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe2+， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe2+， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

Signal mining and analysis of selinexor adverse events / 中国药房

OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

Survival rate and quality of life in patients with liver cirrhosis complicated with bacterial infection / 公共卫生与预防医学

Objective To analyze the short-term survival and prognostic quality of life of patients with liver cirrhosis complicated by bacterial infection. Methods This study collected and analyzed 300 patients with liver cirrhosis complicated with infection who were hospitalized in the First Affiliated Hospital of Hebei North University, and followed up to discuss their survival and quality of life. Results In this study, the top two causes of infection were spontaneous bacterial peritonitis (60.67% of patients) and pneumonia (50.67% of patients). The second causes were urinary tract infections (15.33%), gastrointestinal infections (12.33%), and other causes. There was no statistically significant difference between male and female patients (P>0.05). In addition, the proportion of hospital infections was 71.00%, and there was no statistically significant difference between male and female patients (P>0.05). A total of 353 strains of pathogenic bacteria were isolated in this study (73.37% of patients with hospital infections). The distribution analysis of pathogenic bacteria showed that the highest proportion of ECO was 35.98%, followed by Klebsiella pneumoniae (18.98%). The distribution trend of 259 strains of pathogenic bacteria among hospital patients was consistent with that of all strains, and the difference was not statistically significant (P>0.05). Gram negative bacteria accounted for 79.60% (281/353) of all detected strains, of which Escherichia coli was mostly detected in patients with spontaneous bacterial peritonitis, Klebsiella Pneumoniae (KPN) and Pseudomonas aeruginosa (PAE) were mostly detected in patients with pneumonia, and Enterococcus (ENF) was mostly detected in patients with urinary tract infection; Among gram-negative bacteria, Staphylococcus epidermidis (SEP) and Staphylococcus aureus (SAU) are mostly found in patients with other infectious causes (blood flow infection, etc.) , and Streptococcus (STR) accounts for a high proportion in patients with Spontaneous bacterial peritonitis. In this study, 9 cases of death prognosis were detected during follow-up, and there was no statistically significant difference in the detection of death prognosis between different bacterial strains in both genders, as well as the difference in detection of death prognosis between hospital infections and out of hospital infections in both genders (P>0.05). There was no statistically significant difference in the detection of death prognosis between males and females due to different causes of infection, P>0.05. The quality of life scores of 291 surviving patients were compared between baseline and follow-up, indicating an increase in follow-up scores, especially in the dimensions of physiological function and physical pain. There was no statistically significant difference between different bacterial strains, infection causes, and hospital/non hospital infections (P>0.05) . Conclusion Spontaneous bacterial peritonitis and pneumonia are the main causes of infection that deserve special attention, and the main pathogens of infection are Gram negative bacteria. Targeted treatment and rehabilitation should be provided for patients with liver cirrhosis complicated by infection. At the same time, the proportion of hospital infections is relatively high, and attention should be paid to, prevention and control measures should be implemented as well.

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single- Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. @*Materials and Methods@#We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. @*Results@#Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. @*Conclusion@#Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Analysis of pathogenic characteristics of enteroaggregative Escherichia coli in children with diarrhea in Shanghai from 2019 to 2021 / 上海预防医学

ObjectiveTo understand the presence of virulence genes， molecular typing characteristics， and antibiotic sensitivity of enteroaggregative Escherichia coli （EAEC） in children with diarrhea in Shanghai， so as to provide a scientific basis for EAEC monitoring and standardized treatment of EAEC infection. MethodsEAEC strains isolated from children （≤5 years old） with diarrhea in six districts of Shanghai were collected as the study subjects. EAEC virulence genes were detected by real-time fluorescence quantitative PCR， molecular typing was performed by pulsed-field gel electrophoresis （PFGE）， and drug susceptibility tests were conducted using the microbroth dilution method. χ2 test and two independent samples t-test were used to compare the differences in virulence genes and antibiotic resistance between suburban and urban EAEC strains. ResultsFrom 2019 to 2021， the overall detection rates of gene aggR， pic and astA of 59 EAEC were 30.5%， 50.8%， and 57.6%， respectively. There was no significant difference in the detection rates of virulence genes between suburban and urban EAEC strains （P>0.05）. PFGE analysis revealed that only two EAEC strains belonged to the same PFGE pattern and were collected from the same hospital， and the overall PFGE patterns were polymorphic. EAEC showed susceptibility to imipenem and colistin E， and the resistance rates to sulfamethoxazole （SXT）， ampicillin （AMP）， nalidixic acid （NAL）， and tetracycline （93.1%， 79.3%， 63.8%， and 58.6%， respectively） were higher than 50.0%. The antibiotic resistance rates of cefazolin （CFZ）， cefotaxime （CTX）， and ciprofloxacin （CIP） were significantly different between EAEC strains from suburban and urban areas （P<0.05）. A total of 47 strains exhibited multi-drug resistance， with the most common resistance spectrum being AMP-SXT-NAL. There was no statistically significant difference in the number of multidrug-resistant EAEC strains between suburban and urban areas （P>0.05）. ConclusionThe EAEC virulence gene assemblages in children with diarrhea in the six districts of Shanghai are diverse， and the molecular typing patterns are relatively scattered， indicating possible cross-infection of homologous strains. Multi-drug resistance in EAEC strains is relatively common， and there is a statistically significant difference in the resistance rates of CFZ， CTX and CIP between urban and suburban EAEC strains. Attention should be given to standardizing the use of clinical antibiotics to effectively control the dissemination of multidrug-resistant EAEC strains.

Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway / 中国中药杂志

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels / 中国中药杂志

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy / 中华胃肠外科杂志

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Research progress of effect of gut microbiota on non-small cell lung cancer / 中国胸心血管外科临床杂志

@#The human gut microbiota regulates many host pathophysiological processes including metabolic, inflammatory, immune and cellular responses. In recent years, the incidence and mortality of lung cancer have increased rapidly, which is one of the biggest challenges in the field of cancer treatment today, especially in non-small cell lung cancer. Animal models and clinical studies have found that the gut microbiota of non-small cell lung cancer patients is significantly changed compared with the healthy people. The gut microbiota and metabolites can not only play a pro-cancer or tumor suppressor role by regulating immune, inflammatory responses and so on, but also be related with radiotherapy and chemotherapy of non-small cell lung cancer and the resistance of immunotherapy. Therefore, gut microbiota and related metabolites can be both potential markers for early diagnosis and prognosis in patients with non-small cell lung cancer and novel therapeutic targets for targeted drugs. This study will review the latest research progress of effect of gut microbiota on non-small cell lung cancer, and provide a new diagnosis and treatment ideas for non-small cell lung cancer.

Prognostic factors of spontaneous rupture hemorrhage in primary liver cancer / 中华肝胆外科杂志

Objective:To explore the independent influencing factors of patients with spontaneous rupture hemorrhage of primary liver cancer (PLC).Methods:A retrospective cohort study was conducted. The clinical data of 128 patients with PLC spontaneous rupture hemorrhage in Ningxia Medical University General Hospital from January 2017 to March 2022 were analyzed, including 108 males and 20 females, aged (53.4±10.6) years. According to different treatment, 128 patients were divided into liver resection group (LR, n=28), interventional group [ n=39, transcatheter arterial chemoembolization (TACE) and transcatheter arterial embolization (TAE)], and conservative group ( n=61). Univariate and multivariate Cox regression was performed to analyze prognostic factors. The LR and TACE groups were subdivided into LR (aLR, n=15), TACE/TAE (aTACE, n=33) and LR+ TACE ( n=19) groups. Kaplan-Meier analysis was performed, and the survival rate was compared by log-rank test. Results:The median survival time of LR group and TACE group was 23 months and 21 months, respectively, with no statistical significance ( P>0.05). The median survival time (38 months) in LR+ TACE group was significantly longer than that in aLR group (10 months) and aTACE group (9 months), and the difference was statistically significant ( P<0.05). Univariate analysis showed that Barcelona Clinical Liver Cancer (BCLC)staging, tumor length ≥10.0 cm, vascular invasion, α-fetoprotein ≥400 μg/L, total bilirubin, prothrombin time and treatment affected overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Multivariate analysis showed that BCLC staging, tumor length ≥10.0 cm, Child-Pugh grade and treatment were independent influencing factors for overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Conclusion:BCLC stage, tumor length ≥10.0 cm, Child-Pugh grade and treatment method are independent predictors of overall survival in patients with spontaneous rupture of PLC. LR combined with TACE therapy can improve the survival and prognosis of patients with spontaneous rupture of primary liver cancer.

The experience and enlightenment of robotic surgery training course in the University of Pittsburgh Medical Center / 中华医学教育探索杂志

Objective:To introduce the experience of robotic surgery training course in the University of Pittsburgh Medical Center.Methods:The specific process of the training course was introduced in detail, and the results of the training course were summarized and analyzed. A total of 15 surgeons completed the first step of the training (operation table simulation training), 14 (93.3%) completed the second step (pancreatoduodenectomy tissue anastomosis simulation training), and 196 cases of tissue anastomosis simulation training were completed. Statistical analysis was performed using STATA and SPSS software. Wilcoxon rank sum test was used to analyze the data.Results:The average scores of the surface validity Likert scale for anastomosis simulation training were: (15/20) for Pancreaticojejunostomy (PJ), (15/20) for Gastrojejunostomy (GJ), and (17/20) for Hepatocholangiojejunostomy (HJ). In the PJ and GJ simulation training, compared with the gold standard, the error rate and OSATS score were significantly improved ( P > 0.05), and the operation time was not significantly reduced ( P < 0.05). In HJ simulation training, the error rate, OSATS score and operation time did not show significant improvement ( P < 0.05). However, it could be concluded that all the simulation operations performed by the trainees after the training were better than the first time, when linear regression and quadratic fitting models were performed to analyze continuous trainings of the trainees as a group. Conclusion:The training course carried out by the University of Pittsburgh Medical Center is valid and effective, and it can be used for reference to explore a way for the development of robotic surgery fitting to the real conditions of our country.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats / 药物分析学报

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Developing a development index system of Shanghai district-level disease prevention and control institutions using the Delphi method / 上海预防医学

ObjectiveTo construct an evaluation index system for the development of district-level disease prevention and control centers according to the requirements of the modernization of Shanghai’s disease control system and public health work practices， and to comprehensively assess the construction and development of district-level disease prevention and control institutions. MethodsAccording to the national and municipal requirements for the development of disease prevention and control institutions， an index framework was proposed through literature search and expert interviews. 39 representative experts in the field of public health at the national， provincial， and municipal （district） levels were selected to participate in the consultation and construction of the index system. The authority coefficient， the coefficient of variation， etc. were used to carry out quality control and determination of each index on the Delphi method. ResultsThe questionnaire response rate was 100%， the expert authority coefficient was 0.86，the degree of familiarity was 0.79， and the judgment basis was 0.92. The coefficients of variation of the necessary indicators in the index system were all <0.25 in the dimension of importance， and there were statistical differences in the statistical test of Kendall’s W coordination coefficients at all levels and dimensions （all P<0.001）. After multiple rounds of consultation， experts reached a consensus， forming a development evaluation index system of district-level CDCs with 6 first-level indicators， 24 second-level indicators， and 105 third-level indicators （including 63 necessary indicators and 42 recommended indicators）. ConclusionThe evaluation index system of Shanghai district-level CDCs based on the Delphi method has good authority， reliability， sensitivity and operability. This indicator system can effectively support the development of Shanghai district-level CDCs， and can be used for evaluation at multiple levels and in an all-round way in the future. The evaluation results can provide an evidence-based basis for the modernization of the disease prevention and control system and the continuous and dynamic updating of the development goals in the future.

Reform and exploration of biopharmaceutics blended teaching in the context of "first-class undergraduate education" / 生物工程学报

In recent years, the biopharmaceutical industry has developed rapidly, creating urgent demand for high-quality, innovative, and application-oriented talents. In the context of "first-class undergraduate education", it is of great significance to reform and explore biopharmaceutics blended learning to foster professional talents who can adapt to the industrial development. The blended teaching of biopharmaceutics course in Hubei University was based on small private online course (SPOC) and ChaoXing platform, aiming to meet the first-class "AIC (advanced, innovation, challenge)". The course strengthened the three phases of teaching: before, during, and after class, and innovated teaching methods actively to achieve curriculum goals, and integrated typical cases organically. In addition, the course improved the discriminative power of assessment by strengthening the formative performance evaluation. Moreover, the course provided guidance for students to improve the learning efficiency through investigating the students' learning behavior and employing the marginal utility curve to analyze the characteristics of group activities. Furthermore, the course also offered students personalized learning guidance based on their career planning. The reform of biopharmaceutics blended teaching has achieved significant outcomes, such as improving students' satisfaction, students' innovation and entrepreneurship ability, and curriculum construction level, thus may serve as a reference for the teaching reform and research of the related courses.

Long-Term Prognosis of Different Reperfusion Strategies for ST-Segment Elevation Myocardial Infarction in Chinese County-Level Hospitals: Insight from China Acute Myocardial Infarction Registry / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals.@*METHODS@#A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality.@*RESULTS@#Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81).@*CONCLUSION@#In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.

Analysis and Promotion Strategy of Medical Students’ Mental Health Status Based on Healthy Personality Orientation / 中国医学伦理学

To understand the positive mental health status of medical students, improve their mental health level, and cultivate medical talents with sound personality and all-round development. Starting from the positive psychological health concept of healthy personality orientation, the Mental Health Scale with a Healthy Personality Orientation for College Students was used to conduct a random sampling survey on 600 medical students in a medical college. The results showed that the mental health score of medical students was (90.13±15.01), which was lower than that of national college students, and their difference was statistically significant (P=0.001). Medical students scored significantly lower than national college students in the three dimensions of happiness experience (P<0.001), interpersonal harmony (P=0.003), and goal pursuit (P=0.008). Moreover, there were group differences in the level and structure of mental health among medical students of different genders, grades, majors, and family origins (P<0.05). Universities should adopt targeted educational measures for different groups of medical students to guide them to cultivate positive psychological qualities and promote their physical and mental health development.

Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Construction of a High-Throughput Mutation Library of Mycobacterium Rifampin Resistance Gene rpoB / 中山大学学报(医学科学版)

ObjectiveTo establish a mutation library of rifampicin resistance gene rpoB. MethodsThe ΔrpoB attB：：rpoB strain of Mycobacterium smegmatis （M. smegmatis） be constructed by homologous recombination and L5 attB phage integration site exchange. Based on the L5 attB plasmid exchange system and resistance selection medium， 48 clones are selected to verify plasmid replacement efficiency. Degenerate primers are designed every 3 bases in the rifampicin resistance determining region （RRDR）， and a full-coverage mutation library of 81 bases in RRDR region is obtained by PCR amplification. The library fragments are seamlessly cloned into the vector and transformed into Escherichia coli （E. coli）to form an E. coli mutation library. Based on the principle of plasmid exchange， the mutant plasmid library is transformed into the M. smegmatis strain ΔrpoB attB：：rpoB， and the original L5 attB site plasmid is replaced to form the M. smegmatis mutant library. The genotype of the library are determined by genome extraction， library construction and high-throughput sequencing. ResultsCompared with the wild-type rpoB gene （5 600 bp）， the amplified fragment of the rpoB knockout strain is 2 200 bp， which proved that the ΔrpoB attB：：rpoB conditional knockout strain of M. smegmatis is successfully constructed. The success rate of plasmid replacement is 100%. There were 540 kinds of single amino acid mutations in both E. coli library and M. smegmatis library， 5 301 kinds of multi-point mutations in E. coli library， and 853 kinds of multi-point mutations in M. smegmatis library. The correlation coefficient between E. coli library and M. smegmatis library is 0.84. ConclusionsWe have developed a strategy to construct a library of mutants targeting the essential mycobacterial gene rpoB， and successfully established a mutant library of rifampicin resistance gene rpoB.

Contamination status and molecular typing of Legionella pneumophila in artificial water environment in Shanghai hospitals from 2019 to 2020 / 环境与职业医学

Background The incidence of Legionnaires' disease is increasing globally and artificial water environment is becoming a common source of outbreaks. Molecular typing techniques can help prevent and control Legionella. Objective To understand the molecular epidemiological characteristics of Legionella pneumophila in artificial water environment of Shanghai hospitals, and provide a scientific basis for the prevention and control of Legionnaires' disease. Methods Water samples were collected from artificial water environment in 14 hospitals from May to October each year from 2019 to 2020 in Shanghai. A total of 984 water samples were collected from 8 Grade-A tertiary hospitals and 6 non-Grade-A tertiary hospitals, including 312 samples of cooling water, 72 samples of chilled water, and 600 samples of tap water. The water samples were isolated and serotyped for Legionella pneumophila and preserved, and the positive rate of Legionella pneumophila in the samples was used as an indicator of contamination. The preserved strains were resuscitated and 81 surviving strains were obtained for pulsed field gel electrophoresis (PFGE) typing analysis. Results A total of 124 Legionella pneumophila positive water samples were detected, with a positive rate of 12.60%. The positive rate was higher in the Grade-A tertiary hospitals (16.54%, 87/526) than in the non-Grade-A tertiary hospitals (8.08%, 37/458) (χ2=15.91, P<0.001). The positive rate of cooling water (23.40%) was the highest among different types of water samples, and the difference was statistically significant (χ2=61.19, P<0.001). The difference in positive rate of tap water was statistically significant among different hospital departments (χ2=11.37, P<0.05). The positive rate in 2019 (15.06%) was higher than that in 2020 (9.84%) (χ2=6.23, P<0.05). From May to October, August had the highest annual average positive rate (16.46%) and October had the lowest (8.54%), but the difference in positive rates among months was not statistically significant (χ2=5.39, P=0.37). The difference in positive rate among districts was statistically significant (χ2=24.88, P<0.001). A total of 131 strains of Legionella pneumophila were isolated, with serotype 1 (80.15%, 105/131) predominating. Among the 81 surviving strains of Legionella pneumophila subjected to PFGE typing, the band-based similarity coefficients ranged from 41.30% to 100%. Among the 29 PFGE band types (S1-S29) recorded, each band type included 1-10 strains, and S28 was the dominant band type. Four clusters (I-IV) of PFGE band types were identified, accounting for 66.67% (54/81) of all strains and containing 13 band types. Conclusion Legionella pneumophila contamination is present in the artificial water environment of hospitals in Shanghai from 2019 to 2020, and the contamination in tap water deserves attention. The detected serotype of Legionella pneumophila is predominantly type 1, and PFGE typing reveals the presence of genetic polymorphism. Therefore, the monitoring and control of Legionella pneumophila in hospital artificial water environment should be strengthened.

Research progress of furmonertinib for EGFR-mutated non-small cell lung cancer / 中国药房

Lung cancer is mainly non-small cell lung cancer （NSCLC）. NSCLC is often associated with epidermal growth factor receptor （EGFR） gene mutations. Currently， epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） are the preferred first-line treatment option for EGFR-mutated NSCLC. Furmonertinib is the second third-generation EGFR-TKI marketed in China， which is developed independently by China. In this review， it is found that furmonertinib has dual activity， strong tumor suppression， high selectivity， and high safety profile， and is effective in the treatment of EGFR-sensitive mutation， EGFR exon 20 T790M resistance mutation， EGFR exon 20 insertion mutation， and central nervous system metastasis NSCLC， and its relevant clinical trials are only enrolled in Chinese patients， which is more guidance for Chinese NSCLC patients in China.