Main Infection Control Measures for Respiratory Infectious Diseases in Medical Institutions and Public Places in China / 中国医学科学院学报

Respiratory infectious diseases (RID) are the major public health problems threatening the people's lives and health.Infection control (IC) is one of the effective tools to contain the occurrence and spread of RID.We collected the articles and data on IC published since January 1,2018 and summarized the achievements,problems,and challenges of IC from administrative control,management control,environment and engineering control,and personal protection in the medical institutions and public places in China.The efforts for IC vary in different regions and medical institutions of different levels.There are still links to be improved for IC from administrative control,management control,environment and engineering control,and personal protection,especially in community-level medical institutions and public areas.It is urgent to strengthen the implementation of IC policies and conduct IC precisely according to local situations.We proposed the following suggestions.First,the existing IC products and tools should be applied to precisely implement the IC measures;second,modern high technology should be employed to develop efficient and convenient IC products and tools;finally,a digital or intelligent IC platform should be built for monitoring infections,so as to contain the occurrence and spread of RID.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Survival analysis of patients with intrahepatic cholangiocarcinoma treated with adjuvant chemotherapy after radical resection based on CoxPH model and deep learning algorithm / 中华外科杂志

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study / 中华外科杂志

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

Isolation, culture and validation of CD34+ vascular wall-resident stem cells from mice / 生理学报

Vascular wall-resident stem cells (VW-SCs) play a critical role in maintaining normal vascular function and regulating vascular repair. Understanding the basic functional characteristics of the VW-SCs will facilitate the study of their regulation and potential therapeutic applications. The aim of this study was to establish a stable method for the isolation, culture, and validation of the CD34+ VW-SCs from mice, and to provide abundant and reliable cell sources for further study of the mechanisms involved in proliferation, migration and differentiation of the VW-SCs under various physiological and pathological conditions. The vascular wall cells of mouse aortic adventitia and mesenteric artery were obtained by the method of tissue block attachment and purified by magnetic microbead sorting and flow cytometry to obtain the CD34+ VW-SCs. Cell immunofluorescence staining was performed to detect the stem cell markers (CD34, Flk-1, c-kit, Sca-1), smooth muscle markers (SM22, SM MHC), endothelial marker (CD31), and intranuclear division proliferation-related protein (Ki-67). To verify the multipotency of the isolated CD34+ VW-SCs, endothelial differentiation medium EBM-2 and fibroblast differentiation medium FM-2 were used. After culture for 7 days and 3 days respectively, endothelial cell markers and fibroblast markers of the differentiated cells were evaluated by immunofluorescence staining and q-PCR. Furthermore, the intracellular Ca2+ release and extracellular Ca2+ entry signaling were evaluated by TILLvisION system in Fura-2/AM loaded cells. The results showed that: (1) High purity (more than 90%) CD34+ VW-SCs from aortic adventitia and mesenteric artery of mice were harvested by means of tissue block attachment method and magnetic microbead sorting; (2) CD34+ VW-SCs were able to differentiate into endothelial cells and fibroblasts in vitro; (3) Caffeine and ATP significantly activated intracellular Ca2+ release from endoplasmic reticulum of CD34+ VW-SCs. Store-operated Ca2+ entry (SOCE) was activated by using thapsigargin (TG) applied in Ca2+-free/Ca2+ reintroduction protocol. This study successfully established a stable and efficient method for isolation, culture and validation of the CD34+ VW-SCs from mice, which provides an ideal VW-SCs sources for the further study of cardiovascular diseases.

Correlation analysis of serum zonulin, ZO-1, TNF-α with severity of acute pancreatitis / 中国医师杂志

Objective:To analyze the correlation between the severity of acute pancreatitis (AP) and the levels of zonulin, zonula occludens protein-1 (ZO-1), tumor necrosis factor -α (TNF -α) in the peripheral blood of patients with acute pancreatitis (AP), and the value of predicting moderate and severe AP.Methods:The clinical data of 115 AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from June 2020 to January 2022 were retrospectively analyzed. They were divided into mild group (69 cases) and moderate severe group (46 cases). The blood levels of zonulin, ZO-1, and TNF-α were measured for all patients on the 1st, 3rd, and 7th day after admission, and the results of the two group tests were compared. The correlation between zonulin, ZO-1, TNF -α and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores on the 1st day was and the value of various indicators for predicting moderate to severe AP were analyzed.Results:The C-reactive protein (CRP) levels of AP patients in the moderate to severe group were higher than those in the mild group, and the difference was statistically significant (all P<0.05). The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group showed an upward trend on the 1st, 3rd, and 7th days after admission. The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group were higher than those in the mild group at the same time point, and the differences were statistically significant (all P<0.05). The APACHE Ⅱ score of AP patients on the first day of admission was positively correlated with the levels of zonulin, ZO-1, and TNF -α ( r=0.736, 0.552, 0.621, all P<0.05). Zonulin had the highest area under the curve (AUC) for predicting moderate to severe AP, at 0.892, with an optimal threshold of 2.075 pg/ml. Zonulin had the highest sensitivity, at 0.804, and ZO-1 had the highest specificity, at 0.926. Using zonulin ≥2.075 pg/ml, ZO-1≥399.4 ng/ml, and TNF -α≥40.88 pg/ml as thresholds; the sensitivity and specificity obtained from parallel experiments were 0.976 and 0.710, respectively; The sensitivity and specificity obtained from the series of experiments were 0.326 and 0.999, respectively. Conclusions:There is a correlation between the serum levels of zonulin, ZO-1, and TNF -α in AP patients and the severity of AP. Zonulin, ZO-1, and TNF -α have certain clinical value in predicting moderate to severe AP.

Effect of hydroxysafflor yellow A on depressive-like behavior and expression of GABAAR protein in hippocampus of chronic restraint stress model mice / 中华行为医学与脑科学杂志

Objective:To investigate the effects of hydroxysafflor yellow A (HSYA) on depressive-like behavior and expression of type A γ-aminobutyric acid receptor(GABAAR)in hippocampus of chronic restraint stress model mice.Methods:The SPF grade male C57BL/6C mice were divided into Control group, HSYA group, Model group, Model + HSYA group and Model + fluoxetine group according to random number table method, with 12 mice in each group.Mice model of depression was established by chronic restraint stress.Mice in HSYA group and Model+ HSYA group were intraperitoneally injected with HSYA(20 mg/kg), mice in Model+ fluoxetine group were injected intraperitoneally with fluoxetine (10 mg/kg), and mice in Control group and Model group administered with 0.9% sodium chloride solution intraperitoneally once a day for 14 days.Then, the forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and the protein expression levels of different subtypes of GABAAR in the hippocampus of mice were determined by Western blot.SPSS 19.0 and GraphPad Prism 8.0 software were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-HSD test was used for further pairwise comparison.Results:(1) In the behavioral tests, there were significant differences in swimming immobility time of FST and tail suspension immobility time of TST among the five groups ( F=21.59, 20.81, both P<0.05). The swimming immobility time ((143.91±9.97) s) and tail suspension immobility time (( 107.00±6.54) s) in Model group were higher than those in Control group ((52.92±6.70) s, ( 43.50±5.96) s, both P<0.05). There were no significant difference in swimming immobility time and tail suspension immobility time between Model+ HSYA group ((26.17±7.69)s, ( 20.17±7.89)s) and Model+ fluoxetine group ((61.60±16.22)s, (34.14±10.74)s)(both P>0.05), but the swimming immobility time and tail suspension immobility time in these two groups were lower than those in Model group (both P<0.05). (2) The Western blot results showed that there were significant differences in the expression of GABAARβ1 and GABAARβ2 protein in hippocampus among the four groups ( F=12.21, 11.40, both P<0.05). The expression levels of GABAARβ1(45.60±10.76) and GABAARβ2 (46.27±4.82) protein in hippocampus of Model group were lower than those in Control group ((100.00±3.44), (100.00±3.26), both P<0.05). Compared to Model group, the expression of GABAARβ1 (79.91±5.00) and GABAARβ2 (79.08±5.53) protein in hippocampus of Model+ HSYA group were higher (both P<0.05). In addition, the expression of GABAARα1 and GABAARγ1 proteins in hippocampus were not significantly different among the four groups( F=0.23, 0.10, both P>0.05). Conclusion:HSYA can effectively alleviate depressive-like behavior in depression model mice, which may be related with the upregulation of GABAARβ1 and GABAARβ2 of hippocampus tissue.

Apolipoprotein E enhances migration of endometrial cancer cells byactivating the ERK/MMP9 signaling pathway / 南方医科大学学报

OBJECTIVE@#To study the role of apolipoprotein E (APOE) in regulating endometrial cancer metastasis and explore the signaling pathway in the regulatory mechanism.@*METHODS@#Human endometrial cancer cell line HEC-1B was transfected with a control siRNA (siCtrl) or a specific siRNA targeting APOE (siAPOE) or with either pEGFP-N1 plasmid or an APOEoverexpressing plasmid. The changes in migration, proliferation, apoptosis and cell cycle of the transfected cells were examined using wound healing assay, Transwell migration assay, MTT assay, flow cytometry, and Hoechst staining. The activity of the ERK/MMP9 signaling pathway in the transfected cells was assessed using RT-qPCR and Western blotting. The expression level of APOE in clinical specimens of endometrial cancer tissues were detected using immunohistochemistry and its correlation with differentiation of endometrial cancer tissues was analyzed.@*RESULTS@#Wound healing assay and Transwell migration assay showed that compared with those in siCtrl group, HEC-1B cells transfected with siAPOE showed significantly reduced migration ability (P < 0.05), whereas APOE overexpression significantly promoted the migration of the cells (P < 0.05). Neither APOE knockdown nor overexpression produced significant effects on HEC-1B cell proliferation as shown by MTT assay and flow cytometry. Hoechst staining revealed that transfection with siAPOE did not significantly affect apoptosis of HEC-1B cells. APOE knockdown obviously reduced and APOE overexpression enhanced ERK phosphorylation and MMP9 expression in HEC-1B cells (P < 0.05). Treatment with U0126 partially reversed the effects of APOE overexpression on ERK phosphorylation, migration and MMP9 expression in HEC-1B cells (P < 0.05). APOE is highly expressed in clinical samples of endometrial cancer tissues as compared with the adjacent tissues.@*CONCLUSION@#APOE is highly expressed in endometrial cancer tissues to promote cancer cell migration by enhancing ERK phosphorylation and MMP9 expression.

A novel nomogram for individualized preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma / 中华外科杂志

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.

Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection / 中华外科杂志

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.

Efficacy and safety of hydroxychloroquine in the treatment of IgA nephropathy: a single-center retrospective analysis / 中华肾脏病杂志

Objective:To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN).Methods:The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi).Results:A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min -1·(1.73 m 2) -1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% ( n=76) and 48.48% ( n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% ( n=85) and 52.78% ( n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% ( n=30) and 53.16% ( n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% ( n=31) and 54.44% ( n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions:HCQ is safe and effective for the treatment of IgAN.

Research on supervision strategy of high risk areas of hospital incorrupt government based on traditional chinese medical theory of preventing diseases / 中华医院管理杂志

In recent years, the frequency of corruption incidents in public hospitals in China has increased, and it is particularly important to strengthen the construction of hospital incorrupt politics. Based on the traditional chinese medical theory of preventing diseases, the author deeply discusse the prevention and control strategies in high-risk areas of public hospitals incorrupt from 3 aspects: prevention before disease onset, prevention of disease from exacerbating and prevention of recovery from relapse. Based on the common problems found in the political inspection of Beijing municipal health system and large-scale hospitals in the latest years, an incorrupt government risks list of high-risk areas in hospital had been sorted out; A tertiary hospital and its 4 entrusted hospitals were selected to conduct self-inspection on the key links of important power activities and authority behaviors in accordance with the incorrupt government risks list, and putting forward targeted supervision strategies for these problems. Since the implementation of supervision strategy for high-risk areas in the tertariy hospital and its 4 entrusted hospitals in May 2021, the number of letters and visits in the 5 aspects of medicine procurement, equipment procurement, consumables and reagents procurement, engineering construction and logistics service procurement were significantly reduced. Based on the traditional chinese medical theory of preventing diseases, the supervision strategy in high-risk areas could effectively improve the pertinence, operability and effectiveness of discipline inspection and supervision in hospital, and provide a reference for the construction of incorrupt government in public hospitals.

Predicting the prognosis of patients with cardiogenic acute stroke based on the nomogram model / 国际外科学杂志

Objective:A nomogram model was constructed to predict poor prognosis and death risk of mechanical thrombectomy in patients with cardiogenic acute stroke.Methods:Selected 276 patients with cardiogenic acute stroke who were treated by Jiangyin Hospital of Traditional Chinese Medicine from January 2016 to June 2020 who underwent mechanical thrombectomy as the research objects, and recorded their general information and laboratory test results. On the 90th day, the subjects were divided into a good prognosis group ( n=122) and a poor prognosis group ( n=154) according to whether the prognosis was poor or not; according to whether they died, the subjects were divided into the survival group ( n=208) and the death group ( n=68). The differences in patient related data were compared, Logistic regression analysis was used to screen for risk factors for poor prognosis and death, the line chart prediction model was established, and the ability of the column chart model to predict poor prognosis and death was evaluated by using the subject work characteristic (ROC) curve. The independent factors selected by multivariate regression analysis were used as predictors to construct a nomogram model to predict the prognosis of mechanical thrombectomy surgery in patients with cardiogenic acute stroke. The degree of calibration and validity of the nomogram model established in this study Make an evaluation. The measurement data that obey the normal distribution were represented by the Mean ± standard deviation ( ± s), and the two independent sample t test was used for the comparison between groups; The comparison of enumeration data between groups adopted chi-square test. Results:Multivariate logistic regression analysis showed age ( OR=1.165; 95% CI: 1.046-1.284; P=0.001), diabetes ( OR=1.123; 95% CI: 1.021-1.225; P<0.001), hemorrhage transformation ( OR= 2.394; 95% CI: 1.857-2.931; P=0.001), recanalization ( OR=0.418; 95% CI: 0.410-0.552; P=0.001), NIHSS score ( OR=1.502; 95% CI: 1.373-1.631); P=0.001), neutrophil count (NEUT) ( OR=1.024; 95% CI: 1.009-1.139; P=0.001), NEUT/lymphocyte count (NLR) ( OR=1.235; 95% CI: 1.112-1.358; P=0.001), D-dimer ( OR=1.939; 95% CI: 1.328-2.551; P=0.001) was an independent risk factor for poor prognosis in patients with cardiogenic acute stroke; age ( OR=1.153; 95% CI: 1.080-1.226; P<0.001), hemorrhage transformation ( OR=6.330; 95% CI: 4.904-7.754; P=0.001), recanalization ( OR=0.418; 95% CI: 0.323-0.514; P=0.001), NIHSS score ( OR=2.051; 95% CI: 1.784-2.338; P=0.001), NEUT ( OR=1.399; 95% CI: 1.275-1.523; P=0.001), NLR ( OR=1.528; 95% CI: 1.414-1.642; P=0.001), D-dimer ( OR=2.391; 95% CI: 1.948-2.834; P=0.001) was an independent predictor of death in patients with cardiogenic acute stroke. The established nomogram model predicted poor prognosis and the area under the ROC curve of death were 0.814 (95% CI: 0.800-0.828) and 0.842 (95% CI: 0.828-0.857). Conclusions:Age, hemorrhage transformation, recanalization, NIHSS score, NEUT, NLR, and D-dimer are all important for the prognosis of patients with cardiogenic acute stroke by mechanical thrombectomy. Diabetes only has a suggestive effect on poor prognosis. The nomogram model established based on these factors can effectively help clinicians evaluate the prognosis of patients, formulate reasonable treatment plans for them, and improve the prognosis.

Establishment of the prediction models of malignant brain edema after vascular recanalization in anterior circulation acute large vascular occlusion stroke / 国际外科学杂志

Objective:Based on Logistic regression and XGBoost algorithm, the prediction model of malignant brain edema (MBE) after vascular recanalization of anterior circulation acute great vessel occlusive stroke (ALVOS) was constructed, and the prediction performance was compared.Methods:A retrospective selection of 382 patients with anterior circulation ALVOS who underwent early endovascular treatment (EVT) in our hospital from March 2014 to June 2020 and successfully recanalized the occluded blood vessel was selected. The patients were divided into the training group ( n=267) and the test group ( n=115) according to the ratio of 7∶3 by the random number table method. According to whether the patients had MBE after successful recanalization of the occluded blood vessels, the training group was divided into the MBE group ( n=41) and non-MBE group ( n=226). The baseline data, treatment and brain computed tomography perfusion(CTP) results of MBE group and non-MBE group in training group and test group were compared respectively, including age, admission score of National Institutes of Health Stroke Scale (NIHSS), grade of cerebral collateral circulation, cerebral blood volume, and so on. Logistic regression model and XGBoost algorithm model were used to screen the predictors of MBE in ALVOS patients with occluded vessels successfully recanalized, and the discrimination and calibration of the two models were compared. The measurement data conforming to the normal distribution were expressed as mean ± standard deviation ( ± s), and the independent sample t test was used for comparison between the two groups. Non-normally distributed measurement data were represented by M ( Q1, Q3), using independent sample Mann-Whitney U test. The chi-square test was used to compare the count data between groups. Results:There was no significant difference in baseline data, treatment status, and cranial computed tomography perfusion (CTP) imaging results of the training group and the test group ( P>0.05). The age, admission systolic blood pressure, admission NIHSS score, proportion of hypertension, proportion of cerebral collateral circulation 0-2, proportion of thrombus removal times> 3 times, time from onset to recanalization, and cerebral blood volume (CBV) of MBE group were (68.95±8.04) years old, (146.71±22.73) mmHg, 17(13, 21) min, 87.80%, 82.93%, 68.29%, (365.64±87.83) min, (32.56±5.73) mL/100 g, obvious higher than the non-MBE group [(60.27±7.13) years old, (137.92±19.58) mmHg, 14(10, 18) points, 73.01%, 60.62%, 2.65%, (307.59±74.05) min, (27.49±5.46) mL/100 g] ( P<0.05). The results of Logistic regression model showed that age, NIHSS on admission, grade of cerebral collateral circulation, times of thrombectomy and time from onset to recanalization were the predictors of MBE after successful recanalization of occluded vessels after EVT in patients with anterior circulation ALVOS ( P<0.05). The top five important feature scores of XGBoost algorithm model were cerebral collateral circulation classification 34, embolectomy times 27, onset to vascular recanalization time 25, admission NIHSS score 22, age 16.In the training set, the area under the curve of the Logistic regression model was 0.816(95% CI: 0.749-0.883), and the Hosmer-Lemeshow test showed that χ2=1.547, P=0.438. The area under the curve of the XGBoost algorithm model was 0.856(95% CI: 0.799-0.913), and the Hosmer-Lemeshow test showed that χ2=1.021, P=0.998. Conclusion:Logistic regression model and XGBoost algorithm model had similar prediction performance for MBE after successful recanalization of occluded vessels after EVT in patients with anterior circulation ALVOS, and collateral circulation classification, number of thrombolysis, time from onset to recanalization, NIHSS score on admission, and age could be used as predictors.

Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells

SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Effects of Chinese herbal decoction on traditional Chinese medicine syndrome, menstrual cycle and sex hormone levels in amenorrhea patients with polycystic ovary syndrome / 中国基层医药

Objective:To investigate the effects of Chinese herbal decoction on traditional Chinese medicine syndrome, menstrual cycle and sex hormone levels in amenorrhea patients with polycystic ovary syndrome.Methods:A total of 124 amenorrhea patients with polycystic ovary syndrome who received treatment in The First People's Hospital of Lianyungang, China between December 2016 and December 2018 were included in this study. They were randomly assigned to receive either oral metformin hydrochloride and clomiphene citrate (control group, n = 62) or oral metformin hydrochloride and clomiphene citrate combined with Chinese herbal decoction (observation group, n = 62). Clinical effective rate and remission of traditional Chinese medicine syndrome were compared between control and observation groups. After treatment, recovery of menstrual cycle, ovulation rate, change of sex hormone level relative to before treatment, and the incidence of adverse reactions were determined in each group. Results:Total clinical effective rate in the observation group was significantly higher than that in the control group [96.77% (60/62) vs. 77.42% (48/62), χ2 = 12.817, P < 0.001]. Total effective rate in term of TCM syndrome in the control group was significantly higher than that in the observation group [83.87% (52/62) vs. 43.55% (27/62), χ2 = 21.800, P < 0.001]. After treatment, serum luteinizing hormone, free testosterone, luteinizing hormone / follicle stimulating hormone, estradiol, follicle stimulating hormone levels in the observation group were (4.28 ± 2.04) U/L, (1.93 ± 0.07) nmol/L, (3.17 ± 1.07), (240.32 ± 30.26) pmol/L, (3.17 ± 1.07) U/L, respectively, which were significantly lower than those in the control group [(6.45 ± 2.11) U/L, (3.27 ± 0.07) nmol/L, (5.73 ± 2.46), (300.32 ± 31.26) pmol/L, (5.12 ± 1.07) U/L), t = 5.822, 106.583, 7.514, 10.859, 10.147, all P < 0.001]. Ovulation rate in the observation group was significantly higher than that in the control group [80.65% (50/62) vs. 51.61% (32/62), χ2 = 11.666, P = 0.001]. Periodic ovulation rate in the observation group was significantly higher than that in the control group [91.94% (57/62) vs. 35.48% (22/62), χ2 = 14.528, P < 0.001]. In the observation group, the proportion of patients having edema, gastrointestinal reaction, vomiting, and diarrhea was 4.84% (3/62), 6.45% (4/62), 11.29% (7/62) and 11.29% (7/62), respectively, and they were 9.68% (6/62), 12.90% (8/62), 19.35% (12/62) and 25.80% (16/62)], respectively in the control group (all P < 0.05). Conclusion:Chinese herbal decoction can help regulate the hormone balance in amenorrhea patients with polycystic ovary syndrome, promote ovulation, eliminate amenorrhea, increase the curative effects on traditional Chinese medicine syndrome, and increase the rate of menstrual cycle recovery.

Clinical study on the treatment of Helicobacter pylori positive chronic superficial gastritis with modified Liqi-Hewei Decoction combined with conventional western medicine therapy / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of modified Liqi-Hewei Decoction combined with conventional western medicine therapy in the treatment of Hp-positive chronic superficial gastritis (CSG). Methods:A total of 96 patients with Hp-positive CSG in the First People’s Hospital of Lianyungang and Changshu No.1 People’s Hospital who met the inclusion criteria between January 2017 and January 2019 were divided into two groups according to the random number table method, with 48 in each group. The control group was treated with conventional western medicine, and study group was additionally given modified Liqi-Hewei Decoction on the basis of control group. Both groups were treated for 8 weeks and followed up for 12 weeks. The TCM symptom score, gastric mucosa and pathological grading were scored before and after treatment. Levels of motilin, gastrin and somatostatin were detected by immunoturbidimetry, and levels of CD3 +, CD4 + and CD8 + were detected by automatic flow cytometry and the ratio of CD4 +/CD8 + was calculated. The Hp negative conversion rate was observed, the adverse reactions were recorded, the clinical efficacy was evaluated and the recurrence rate was statistically analyzed. Results:The Hp negative conversion rate was 89.6% (43/48) in study group and was 72.9% (35/48) in control group, where the difference was statistically significant ( χ2=4.376, P=0.036). The total effective rate was 95.8% (46/48) in study group and was 83.3% (40/48) in control group ( χ2=5.031, P=0.025). After treatment, the scores of epigastric pain, upper abdominal fullness, acid reflux, belching and poor appetite in the study group were significantly lower than those in control group ( t=8.919, 3.971, 7.949, 8.171, 9.865, all Ps<0.01). The scores of gastric mucosa and pathological grading were significantly lower than those in control group ( t=13.705, 15.495, all Ps<0.001). After treatment, the levels of gastrin [(126.15 ± 14.36) ng/L vs. (152.38 ± 17.51) ng/L, t=8.025], motilin [(93.59 ± 11.87) ng/L vs. (102.48 ± 14.68) ng/L, t=3.263] and somatostatin [(36.76 ± 8.97) ng/L vs. (40.84 ± 10.68) ng/L, t=2.027] in the study group were significantly lower than those in the control group ( P<0.01 or P<0.05). The levels of CD3 +, CD4 + and CD4 +/CD8 + were significantly higher than those in the control group ( t=6.883, 6.720, 4.306, all Ps<0.001). The recurrence rate was 4.3% (2/46) in the study group and was 17.5% (7/40) in the control group ( χ2=3.950, P=0.046). During treatment, the incidence rate of adverse reactions was 8.3% (4/48) in the study group and was 12.5% (6/48) in the control group ( χ2=0.446, P=0.504). Conclusion:Modified Liqi-Hewei Decoction combined with conventional western medicine therapy can effectively improve the levels of gastrointestinal hormones and clinical symptoms, enhance the immunity and Hp negative conversion rate, and reduce the recurrence rate of patients with Hp-positive CSG.

Effect of thrombin concentration on the prevention of postoperative cerebrospinal leakage by fibrin glue / 中国组织工程研究

BACKGROUND: Fibrin glue is commonly used to prevent postoperative cerebrospinal fluid leakage from dural injuries. However, fibrin glue with standard-concentration thrombin coagulates too fast, resulting in poor adhesion of dural mater. Effect of low-concentration thrombin fibrin glue on sealing dural injuries to prevent cerebrospinal fluid leakage is unclear. OBJECTIVE: To compare the effect of low-concentration thrombin and standard-concentration thrombin on the prevention of cerebrospinal fluid leakage from dural injuries by fibrin glue. METHODS: Forty patients including 25 males and 15 females with dural injuries admitted at Fifth People’s Hospital of Chengdu from May 2017 to December 2019 were enrolled. Patients were randomly divided into two groups, 20 patients in each group. In low-concentration thrombin group, dural injuries were sealed with fibrin glue prepared with low-concentration thrombin solution (100 IU/mL). In standard-concentration thrombin group, dural injuries were sealed with fibrin glue prepared with standard-concentration thrombin solution (500 IU/mL). All patients were followed up for 2 months. The incidence of cerebrospinal fluid leakage, cumulative drainage flow, drainage duration and incision complications were compared between the two groups. The study was approved by Ethics Committee of Fifth People’s Hospital of Chengdu. RESULTS AND CONCLUSION: (1) The incidence of cerebrospinal leakage, accumulative volume and duration of drainage in the low-concentration thrombin group were lower than those of standard-concentration thrombin group (P 0.05). (3) These results indicate that fibrin glue prepared with low-concentration thrombin solution decreases the rate of cerebrospinal leakage, reduces the drainage volume and shortens the duration of drainage, which is demonstrated to be an effective strategy for sealing dural injuries.

Self-assembly performance of triterpene natural small molecules and their application in synergistic antitumor chemotherapy / 药学学报

Natural biocompatible nanomaterials such as self-assembled triterpene natural small molecule products with favorable anticancer activity show great potential for biomedical application. However, the mechanisms of their molecular self-assembled structures have not been investigated systematically, while there are still few reports of the natural active carrier for drug delivery. Herein, in this work, we further explored the molecular assembly mechanism and common regularity of tetracyclic triterpenes ergosterol, stigmasterol as well as pentacyclic triterpenes glycyrrhetinic acid and ursolic acid, which suggested that the coplanarity and orderliness of molecular arrangements which are speculated to be responsible for their self-assembly into the spherical, rod-like or lamellar nanostructure. Besides, ergosterol (ET) with better anticancer activity was chosen as a representative substance for construction of the synergistic antitumor nanodrug. By intermolecular hydrogen bonding and π-π stacking, chemotherapeutic drug paclitaxel (PTX) was encapsulated into ET-PTX NPs successfully. Then, the anti-cancer efficacy of the tumor-bearing mice was evaluated according to the protocol approved by the Experimental Animal Research Center of Harbin Medical University. The resulting nanodrug exhibited excellent biosafety and enhanced in vivo anticancer activity efficiency of 52.3%, higher than free PTX (29.4%) or ET NPs (32.5%) alone, further verifying the potential medical application value of triterpene natural products. This work provides not only a theoretical basis for exploring the self-assembly behavior of small molecule natural products, but also a promising perspective for the fabrication of active natural biocompatible nanodrug delivery systems for synergistic antitumor therapy and other biomedical applications.

Epidemiological and clinical characteristics of 75 cases with hemorrhagic fever with renal syndrome / 中华传染病杂志

Objective:To investigate the epidemiological and clinical features of patients with hemorrhagic fever with renal syndrome (HFRS) from 2017 to 2019.Methods:Seventy-five patients with HFRS from the Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University during January 1, 2017 to December 31, 2019 were included. The data of epidemiology, clinical symptoms, blood routine, urine routine, serum creatinine, liver function and other laboratory examination indexes were retrospectively analyzed. The measurement data with skewness distribution were expressed by M( QR) and compared by nonparametric test. Multivariate logistic regression analysis was used to analyze disease-related risk factors. Results:The 75 patients were mainly located in the western and northern regions of Anhui Province. A total of 37 cases (49.3%) were infected during November, December and January next year. Fifty-four (72.0%) patients were farmers and 10(13.3%) patients had a clear history of rodent contact. Only 19(25.3%) patients had typical clinical manifestations of "three red and three pain" . Fifty-eight (77.3%) patients had elevated white blood cell count, 67(89.3%) patients had decreased platelet count, 55(73.3%) patients had urinary protein + + + , 65(86.7%) patients had abnormal urinary occult blood, and 67(89.3%) patients had elevated serum creatinine. The serum creatinine and potassium levels in 31 severe and critical patients were 495(301) μmol/L and 4.14(0.77) mmol/L, respectively, which were both higher than those in 44 mild and moderate patients (235(289) μmol/L and 3.65(1.02) mmol/L, respectively). The differences were both statistically significant ( Z=-3.187 and -2.796, respectively, both P<0.01). Multivariate logistic regression analysis showed that serum creatinine (odds ratio ( OR)=1.005, 95% confidence interval ( CI)1.002-1.008) and serum potassium ( OR=2.632, 95% CI 1.098-6.313) were independent risk factors for disease severity. All patients received comprehensive medical treatment, and 27 patients received renal replacement therapy. Sixty-eight patients had good prognosis and four patients died. Conclusions:HFRS is still common in the rural area in winter and spring. Patients with atypical clinical manifestations and severe and critical patients should be intensively monitored.