Preliminary study on the value of fetal MRI lung volume and mediastinal shift angle for predicting prognosis of left congenital diaphragmatic hernia / 中华放射学杂志

Objective:To explore the value of fetal lung volume and mediastinal shift angle (MSA) based on fetal MRI in predicting the prognosis of congenital diaphragmatic hernia (CDH).Methods:Fetuses with left CDH that did fetal MRI in Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine from September 2016 to January 2022 were retrospectively collected. There were 65 patients, and their gestational age was 29 (26, 35) weeks when they were diagnosed with left CDH by MRI. Observed fetal lung volume and MSA were measured based on fetal MRI, and observed/expected lung volume (o/eFLV) based on gestational age was calculated. The clinical data were collected from birth to discharge, and patients were divided into survival group and death group in case of prognosis at discharge, with 54 cases in the survival group and 11 cases in the death group. The student′s t test was used to compare the difference of o/eFLV and MSA between the survival group and the death group, and the receiver operating characteristic (ROC) curve was used to evaluate the value of o/eFLV and MSA in predicting the prognosis of left CDH. Results:The o/eFLV of the survival group was 51.5%±18.3%, higher than that of the death group (27.8%±4.4%), and the difference was significant ( t=8.29, P<0.001). The MSA of the survival group was 33.1°±1.2°, lower than that of the death group (41.8°±2.7°), and the difference was significant ( t=-11.15, P<0.001). The area under the ROC curve (AUC) of o/eFLV to predict the fetal survival or death was 0.939 (95%CI 0.851-0.983), the cutoff value was 33.8%, the sensitivity was 100%, the specificity was 88.9%. The AUC of MSA was 0.998 (95%CI 0.941-1.000), the cutoff value was 37.2°, the sensitivity was 100%, the specificity was 98.2%. Conclusions:The o/eFLV and MSA that were measured based on fetal MRI can effectively predict the fetus′s prognosis with left CDH.

Analyses on employment of clinical medical students of eight-year program and its implications to talent cultivation / 中华医学教育探索杂志

Objective:To analyze employment status and its tendency of eight-year program clinical medical graduates and explore its implications to talent cultivation using employment data from a university in Beijing.Methods:Descriptive analysis was used in this study. Indicators that were analyzed included quantity of employment, employment rate, employment region and specialty.Results:Between 2009 and 2021, a total of 2 281 eight-year clinical medical students graduated in the university. Among them, 2 188 (96.0%) of them were employed in the year of graduation. On average, 90.8% (2 034/2 241) of them were employed by medical institutions although the percentage decreased over years. A majority of them chose to work in economically developed provinces of eastern China. Those chose to work in Beijing accounted for 78.7% (1 723/2 188), the highest percentage among all provinces. The top two specialties of choice were surgery and internal medicine, which respectively accounted for 33.0% (753/2 281) and 24.4% (557/2 281). Only a few of them chose to study some specialties that were challenged by a serious shortage of physicians, including pediatrics, mental diseases and mental health.Conclusion:Although the employment status of eight-year clinical medical graduates are good, it is still necessary to pay attention to the new tendency of employment, and further improve training scheme. Meanwhile, more guidance on choice of secondary specialties are needed to build a competent talent team for specialty development. Finally, education of curriculum iedology and politics should be strengthened to encourage them to work in specialties and remote provinces that face a serious shortage of physicians.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Challenges to global pertussis prevention and control / 中华流行病学杂志

Pertussis is an acute, highly infectious respiratory disease caused by Bordetella pertussis, and is one of the leading causes of infant disease and death worldwide. The pertussis vaccine has been used in the expanded program on immunization globally since 1974 and the vaccination coverage remains high. In recent years, the pertussis incidence rate increased, even pertussis outbreaks occurred, in more and more countries or areas after years with low incidence level. The disease burden of pertussis has been seriously underestimated, and the prevention and control of pertussis is facing many challenges. This article reviews the epidemic status of pertussis worldwide, the factors affecting the reemergence of pertussis, and the challenges in the prevention and control to provide a reference for prevention and control of pertussis.

Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China / 中华流行病学杂志

Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.

Establishment of artificial neural network model for predicting lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer / 中华胃肠外科杂志

Objective: To establish a neural network model for predicting lymph node metastasis in patients with stage II-III gastric cancer. Methods: Case inclusion criteria: (1) gastric adenocarcinoma diagnosed by pathology as stage II-III (the 8th edition of AJCC staging); (2) no distant metastasis of liver, lung and abdominal cavity in preoperative chest film, abdominal ultrasound and upper abdominal CT; (3) undergoing R0 resection. Case exclusion criteria: (1) receiving preoperative neoadjuvant chemotherapy or radiotherapy; (2) incomplete clinical data; (3) gastric stump cancer.Clinicopathological data of 1231 patients with stage II-III gastric cancer who underwent radical surgery at the Fujian Medical University Union Hospital from January 2010 to August 2014 were retrospectively analyzed. A total of 1035 patients with lymph node metastasis were confirmed after operation, and 196 patients had no lymph node metastasis. According to the postoperative pathologic staging. 416 patients (33.8%) were stage Ⅱ and 815 patients (66.2%) were stage III. Patients were randomly divided into training group (861/1231, 69.9%) and validation group (370/1231, 30.1%) to establish an artificial neural network model (N+-ANN) for the prediction of lymph node metastasis. Firstly, the Logistic univariate analysis method was used to retrospectively analyze the case samples of the training group, screen the variables affecting lymph node metastasis, determine the variable items of the input point of the artificial neural network, and then the multi-layer perceptron (MLP) to train N+-ANN. The input layer of N+-ANN was composed of the variables screened by Logistic univariate analysis. Artificial intelligence analyzed the status of lymph node metastasis according to the input data and compared it with the real value. The accuracy of the model was evaluated by drawing the receiver operating characteristic (ROC) curve and obtaining the area under the curve (AUC). The ability of N+-ANN was evaluated by sensitivity, specificity, positive predictive values, negative predictive values, and AUC values. Results: There were no significant differences in baseline data between the training group and validation group (all P>0.05). Univariate analysis of the training group showed that preoperative platelet to lymphocyte ratio (PLR), preoperative systemic immune inflammation index (SII), tumor size, clinical N (cN) stage were closely related to postoperative lymph node metastasis. The N+-ANN was constructed based on the above variables as the input layer variables. In the training group, the accuracy of N+-ANN for predicting postoperative lymph node metastasis was 88.4% (761/861), the sensitivity was 98.9% (717/725), the specificity was 32.4% (44/136), the positive predictive value was 88.6% (717/809), the negative predictive value was 84.6% (44/52), and the AUC value was 0.748 (95%CI: 0.717-0.776). In the validation group, N+-ANN had a prediction accuracy of 88.4% (327/370) with a sensitivity of 99.7% (309/310), specificity of 30.0% (18/60), positive predictive value of 88.0% (309/351), negative predictive value of 94.7% (18/19), and an AUC of 0.717 (95%CI:0.668-0.763). According to the individualized lymph node metastasis probability output by N+-ANN, the cut-off values of 0-50%, >50%-75%, >75%-90% and >90%-100% were applied and patients were divided into N0 group, N1 group, N2 group and N3 group. The overall prediction accuracy of N+-ANN for pN staging in the training group and the validation group was 53.7% and 54.1% respectively, while the overall prediction accuracy of cN staging for pN staging in the training group and the validation group was 30.1% and 33.2% respectively, indicating that N+-ANN had a better prediction than cN stage. Conclusions: The N+-ANN constructed in this study can accurately predict postoperative lymph node metastasis in patients with stage Ⅱ-Ⅲ gastric cancer. The N+-ANN based on individualized lymph node metastasis probability has better accurate prediction for pN staging as compared to cN staging.

Effects on extravascular lung water of lung protective ventilation strategy applied on piglets with acute respiratory distress syndrome induced by paraquat / 中华劳动卫生职业病杂志

Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established (P<0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant (P<0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) (P<0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline (P<0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group (P<0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Revealing characteristics and rules of acupoint sensitization phenomena: based on knee osteoarthritis / 中国针灸

OBJECTIVE@#To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion.@*METHODS@#In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint.@*RESULTS@#Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients.@*CONCLUSION@#It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.

Relationship between cognitive function and brain event-related potentials in patients with lacunar cerebral infarction / 中国综合临床

Objective:To investigate the relationship between cognitive function and brain event-related potential in patients with lacunar cerebral infarction.Methods:A total of 464 patients with lacunar cerebral infarction admitted to the Department of Neurology, Kailuan General Hospital from 2014 to 2019 were prospectively selected as observation subjects (case group). According to mini-mental state examination (MMSE) score, the patients in the case group were divided into 352 cases of lacunar cerebral infarction with normal cognition and 112 cases of mild cognitive impairment. At the same time, 100 healthy volunteers were selected as the control group. All subjects were assessed by simple intelligent mental state, Zung self-rating anxiety scale, Zung self-rating depression scale and brain event-related potential P3a and P3b. The measurement data of normal distribution adopts one-way ANOVA, the measurement data of non normal distribution adopts Kruskal Wallis H test, and the counting data adopts χ2. Multivariate statistical analysis was performed by unconditional Logistics (stepwise method). Results:The proportions of smokers in control group, lacunar cerebral infarction cognitive normal group and lacunar cerebral infarction mild cognitive impairment group were 20.00% (20/100), 38.07% (134/352) and 46.42% (52/112), respectively. The proportions of drinkers were 18.00% (18/100), 33.24% (117/352), 33.93% (38/112), respectively. The proportions of hypertension were 38.00% (38/100), 58.24% (205/352), 59.82% (67/112), respectively. The proportions of hyperhomocysteinemia were 19.00% (19/100), 34.00% (120/352) and 68.75% (77/112), respectively, and the differences among the three groups were statistically significant ( χ2 values were 15.66, 7.91, 11.86 and 54.57, respectively; P<0.001, 0.019, 0.003, <0.001). The peak latency CZ leads of visual P3b wave group N2 were (271.48±40.65), (285.67±44.08) and (290.57±68.41) ms, respectively. PZ leads were (276.70±50.92), (287.86±43.28) and (312.16±62.75) ms. P3b peak latency FZ leads were (392.67±42.50), (405.82±52.43) and (410.34±64.27) ms. CZ leads were (395.04±42.44), (412.51±55.86) and (433.28±66.32) ms. PZ leads were (398.24±40.93), (411.17±49.48) and (435.78±67.69) ms. N2 amplitude CZ leads were (-3.99±2.81), (-3.60±3.00) and (-2.70±2.37) μV, PZ leads were (-3.18±2.69), (-2.91±2.62) and (-1.87±2.89) μV, respectively. Leads P3b amplitude of FZ were 5.27 (3.27, 7.40), 4.21 (2.31, 6.49) and 3.12 (1.61, 5.08) μV. CZ leads were 4.81 (2.78, 6.71), 4.15 (2.76, 6.16) and 3.51 (1.75, 5.15) μV. PZ leads were 5.17 (3.03, 6.97), 4.40 (2.89, 6.12) and 3.43 (1.52, 5.34) μV. There were statistically significant differences among the 3 groups ( F=3.29, 14.49, 3.95, 11.73, 14.06, 5.66 and 3.57, H=18.23, 10.33,18.25; P=0.027, <0.001, 0.025, <0.001, <0.001, 0.004, 0.042, <0.001, 0.006, <0.001). The peak latency FZ leads of visual P3a wave group N2 were 265.00 (256.00, 286.00), 277.00(260.00,300.00), 282.00(270.00,304.00) ms, respectively. CZ leads weres 274.00(255.00,305.00), 285.00(262.00,329.00), 293.50(270.00,346.00) ms. P3a peak latency FZ leads were (413.83±49.58), (429.83±55.38) and (449.04±54.79) ms, CZ leads were (441.53±61.78), (457.12±69.29) and (460.23±72.24) ms. PZ leads were (430.14±54.53), (462.31±69.2) and (470.02±74.92) ms. N2 amplitude FZ leads were (-6.34±3.13), (-5.72±2.96) and (-4.92±2.05) μV, respectively. Leads P3a amplitude of FZ were 4.00 (2.28, 5.55), 3.15 (2.14, 4.91) and 2.80 (2.19, 4.19) μV. CZ lead were 3.37 (1.98, 4.66), 2.73 (1.70, 3.97) and 2.41 (1.64, 3.45) μV. There were statistically significant differences among the three groups ( H=13.92, 8.65, 9.17, 10.02, F=8.18, 6.33, 10.73, 4.62, P =0.001,0.013,0.010,0.007, <0.001,0.002, <0.001,0.010). Logistic regression analysis showed that alcohol consumption, P3b peak latency and wave amplitude PZ lead, N1 wave amplitude of visual P3a group FZ lead were the influencing factors of MMSE ( OR=0.04, 1.01, 0.76, 1.51, 95% Cl were 0.00-0.30, 1.00-1.03, 0.59-0.97, 1.08-2.10, P=0.002,0.007,0.029,0.016). Conclusion:The peak latency and amplitude of endogenous psychological cognitive potentials N2, P3b and P3a of event-related potentials P3b and P3a in patients with lacunar cerebral infarction were prolonged and decreased. At the same time, with the occurrence of clinical cognitive impairment, the peak latency and amplitude of these cognitive potentials were further prolonged and decreased more significantly. Alcohol consumption, P3b peak latency and PZ lead of visual P3b wave group, and FZ lead of N1 wave of visual P3a wave group were the influencing factors of simple intelligent mental state.

Antiviral effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism / 药学学报

To investigate the effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism, we used Huh7, Huh7.5, H460, and C3A cell lines as in vitro models to evaluate the cytotoxicity and antiviral activity of FFYH by observation of cell pathogenic effect (CPE); and then the inhibitory effect of FFYH on the transcription expression of coronavirus RNA and inflammatory factor mRNA were evaluated by quantitive reverse transcription PCR (qRT-PCR); finally, the inhibitory effect of FFYH on the expression of coronavirus protein and its underlying mechanism against coronavirus were investigated by Western blot and immunofluorescence. Our results indicated that 50% toxic concentration (TC50) FFYH on Huh7, Huh7.5, H460, and C3A cells were 2 035.21, 5 245.69, 2 935.28 and 520 µg·mL-1, respectively; 50% inhibitory concentration (IC50) of FFYH on HCoV-229E in Huh7 and Huh7.5 cells were 438.16 and 238.54 µg·mL-1 with safety index (SI) of 4.64 and 21.99, respectively; IC50 of FFYH on HCoV-OC43 in H460 cells was 165.13 µg·mL-1 with SI of 17.78. Moreover, FFYH not only could inhibit the replication of coronaviruses (HCoV-OC43 and HCoV-229E) through inhibiting the transcription of viral RNA and the expression of viral protein, but also effectively suppress the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) at mRNA level caused by coronaviruses, which might be associated with the inhibitory effect of FFYH on mitogen-activated protein kinase (MAPK) pathway and the nuclear translocation of nuclear transcription factor-κB (NF-κB). In summary, our results demonstrated that FFYH exhibited a good in vitro anti-coronavirus effect, which provides a theoretical basis for its clinical use in the treatment of anti-coronavirus pneumonia.

Value of metagenomic next-generation sequencing in children with severe infectious diseases / 中国当代儿科杂志

OBJECTIVES@#To study the application value of metagenomic next-generation sequencing (mNGS) in children with severe infectious diseases.@*METHODS@#An analysis was performed on the clinical data and laboratory test results of 29 children with severe infection who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to December 2020. Conventional pathogen culture was performed for the 29 specimens (27 peripheral blood specimens and 2 pleural effusion specimens) from the 29 children, and mNGS pathogen detection was performed at the same time.@*RESULTS@#Among the 29 children, 2 tested positive by conventional pathogen culture with 2 strains of pathogen, and the detection rate was 7% (2/29); however, 20 children tested positive by mNGS with 38 strains of pathogen, and the detection rate was 69% (20/29). The pathogen detection rate of mNGS was significantly higher than that of conventional pathogen culture (P<0.05), and mNGS could detect the viruses, fungi, and other special pathogens that conventional pathogen culture failed to detect, such as Orientia tsutsugamushi. The univariate analysis showed that gender, routine blood test results, C-reactive protein, procalcitonin, D-dimer, radiological findings, and whether antibiotics were used before admission did not affect the results of mNGS (P>0.05).@*CONCLUSIONS@#Compared with conventional pathogen culture, mNGS is more sensitive for pathogen detection, with fewer interference factors. Therefore, it is a better pathogenic diagnosis method for severe infectious diseases in children.

A metabolite of Danshen formulae (IDHP) induces angiogenesis and protects rat brains against focal ischemia via CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling / 中国药理学与毒理学杂志

OBJECTIVE Only limited number of drugs are currently available for treating ischemic stroke. Therapeu?tic angiogenesis has recently emerged as one of the most promising therapies for cerebral ischemic injury. Isopropyl-β-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (IDHP) is a metabolite derived from the botanical formulation for Dantonic?. Here, we investigated the angiogenic efficacy of IDHP in cerebral ischemia. METHODS The in vivo effects of IDHP were evaluated in the C57BL/6 mouse Matrigel plug and rat transient middle cerebral artery occlusion (tMCAO) models. Primary human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC) were used to explore the effects of IDHP on stimulating proliferation, migration and tube formation in vitro. ELISA and Western blotting were used to quantitate the release and expression of relevant target molecules and signaling path?ways. RESULTS IDHP reduced infarct volume and improved sensorimotor function in rats subjected to tMCAO by pro?moting angiogenesis, and promoted Matrigel neovascularization in mice. Moreover, IDHP produced a biphasic modula?tion on proliferation and migration both in HUVEC and HBMEC. It also induced tube formation in a 12-day HUVEC-HDF co-culture model and in Matrigel assays. IDHP-induced angiogenesis was accompanied by increased levels of p-AMPKα (Thr172) and p-eNOS (Ser1177) both in vitro and in vivo, and the decreased level of VEGF in rat brains on day 1 whereas enhanced level of VEGF on day 3 and 7 after tMCAO. Mechanistically, AMPK knockdown or pharmacologi?cally inhibiting AMPK and its upstream kinases (CaMKKβ) inhibited the eNOS phosphorylation induced by IDHP in HUVEC. Furthermore, selective eNOS inhibitor (L-NIO), selective CaMKKβ inhibitor (STO) and AMPKa inhibitor (Com?pound C) blocked the capillary-like tube formation in the co-culture model induced by IDHP (10 nmol · L-1). CONCLU?SION Collectively, these findings showed that IDHP protected rats from cerebral ischemia-reperfusion injury by promot?ing angiogenesis via activating CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling, and suggest it to be a promising new drug candidate for the prevention and/or treatment of cerebral ischemia and other vascular occlusive diseases.

Influence factors of depression in patients with lacunar cerebral infarction with mild cognitive impairment / 中国综合临床

Objective:To observe the related factors of depression in patients with lacunar cerebral infarction with mild cognitive impairment.Methods:From 2016 to 2019, 114 patients with mild cognitive impairment of lacunar cerebral infarction in Kailuan General Hospital were selected as the research objects.MRI brain scan was completed within 72 hours after admission, and Zung′s self rating Depression Scale (SDS) was used to evaluate emotion within 1 week.According to the results of SDS, 69 patients with mild cognitive impairment and no depression of lacunar infarction were selected as the control group, and 45 patients with mild cognitive impairment and mild depression of lacunar infarction were selected as the case group.The general clinical data, the proportion of patients with lacunar infarction in different brain regions and cognitive function of the two groups were observed.Logistic regression method was used to analyze the risk factors of depression in patients with mild cognitive impairment of lacunar infarction, and the characteristics of clinical somatization symptoms were observed.Results:(1)There were 53 males (76.81%, 53/69) and 16 females (23.19%, 16/69) in the control group, 29 males (64.44%, 29/45) and 16 females (35.55%, 16/45) in the case group, and the difference between the two groups was statistically significant ( P=0.049). Hyperhomocysteinemia in the control group and the case group was 31.88% (22/69) and 53.33%(24/45), respectively, with statistically significant differences between the two groups ( P=0.003). (2) The incidence rates of lacunar infarction in basal ganglia and oval center was 80% (36/45) and 71.11% (32/45) in case group respectively, and 59.42% (41/69) and 18.84% (13/69) in control group respectively.The difference between two groups was statistically significant ( P values were 0.001 and <0.001), and there was no significant difference in infarct size in other regions ( P>0.05). (3) The rate of impaired attention and computing power in the case group was 88.89%(40/45), which was higher than that in the control group 78.26%(54/69), and the difference was statistically significant ( P=0.036). (4) Multivariate Logistic regression analysis showed that hyperhomocysteemia ( OR=2.659, 95% CI 1.041-6.793, P<0.05) and central oval infarction ( OR=10.332, 95% CI 4.069-26.235, P<0.01) were independent risk factors for mild cognitive dysfunction and depression in lacunar cerebral infarction.(5) The proportion of insomnia and tears with somatization symptoms in the case group was 35.56%(16/45) and 37.77%(17/45), respectively, which were higher than that in the control group 8.70%(6/69) and 2.90%(2/69), respectively, with statistically significant differences (all P<0.001). Conclusion:Hyperhomocysteinemia and hemioval central cerebral infarction are independent risk factors for depression in patients with lacunar cerebral infarction with mild cognitive dysfunction, accompanied by somatization symptoms of insomnia and tearing.

Radiofrequency catheter ablation of ventricular tachycardia in patients post surgical repair of tetralogy of Fallot / 中华心血管病杂志

Objective: To investigate the clinical and electrophysiological features of ventricular tachycardia (VT) in tetralogy of Fallot (TOF) patients post surgical repair (rTOF) and to analyze the therapeutic effect and prognosis of radiofrequency ablation of rTOF-VT. Methods: This is a retrospective study. Consecutive patients with rTOF-VT, who were treated in Fuwai Hospital from January 2015 to March 2020, were enrolled. All the patients underwent right ventricular voltage mapping following routine cardiac electrophysiological examination, followed by linear or homogenizing radiofrequency ablation based on the low-voltage substrate. The clinical features, 3-dimentional electrophysiological substrate mapping, radiofrequency ablation and long-term prognosis of the enrolled patients were analyzed. Acute ablation success was defined as completion of linear or homogenizing ablation or intraoperative evoked VT as destination of the procedure. Patients were followed up at 3 and 6 months post operation and every year thereafter. The endpoints were sudden cardiac death (SCD) and recurrence of ventricular tachycardia. Results: A total of 20 patients with rTOF-VT were enrolled including 14 males with an age of (35.8±11.8) years. The electrocardiogram identified 23 types of ventricular tachycardia, 19 of which were originated from right ventricular inflow tract outlet. The most common clinical manifestations were heart murmur (19 cases, 95%) and syncope (4 cases, 25%). Electroanatomical substrate mapping was performed in 20 patients and evidenced localized or diffuse scar or low-voltage area of right ventricle. Intraoperative electrophysiological tests provoked ventricular tachycardia in 6 patients (30%), including 5 patients with hemodynamics disturbance. The acute success rate of radiofrequency ablation was 95% (19/20). The follow-up time was (31.1±17.7) months and the recurrence rate of ventricular tachycardia was 30% during follow-up period and 5 cases received repeat radiofrequency ablation and there was no recurrent ventricular tachycardia during follow-up post repeat radiofrequency ablation. Conclusions: The voltage substrate mapping under sinus rhythm is a feasible mapping method for rTOF-VT. Linear or flaky radiofrequency ablation of the slow conduction zone is safe and effective treatment strategy, the recurrence rate after the first radiofrequency ablation is still high, and the effectiveness of repeat radiofrequency ablation is satisfactory in this patient cohort.

Current status and quality analysis of interventional therapy for patients with atrial fibrillation in China / 中华心血管病杂志

Objective: To define the current status and analyze the medical quality of interventional therapy for patients with atrial fibrillation (AF) in China. Methods: This survey was performed in all seven large regions of China, one to three regional major medical centers were selected from each region. Medical records of patients underwent interventional therapy for AF in the year 2017 were randomly inspected. CHA2DS2-VASc score, prescribed anticoagulant after ablation, indication of left atrial appendage occlusion (LAAO), and complications in the medical records were analyzed. Results: A total of 10 800 AF catheter ablations and 447 LAAOs were performed in 17 regional medical centers in 2017. There were 10/17 centers performing AF catheter ablation<500 cases and 7/17 centers performing LAAO<20 cases. A total of 1 347 cases of catheter ablation and 160 cases of LAAO were selected for further analysis. Among all selected cases, 15.8% (238/1 505) non-valvar AF cases recorded CHA2DS2-VASc scores. The anticoagulation rate after AF catheter ablation was 98.6% (1 328/1 347), anticoagulation rate was higher than 90% in 16 out of 17 centers. The complication and severe complication rates of AF catheter ablation were 0.9% (12/1 347) and 0.4% (5/1 347), respectively. The differences of complication and severe complication rates in AF catheter ablation were similar between centers performing<500 cases and centers performing ≥500 cases (0.5% (2/413) vs. 1.1% (10/934), P>0.05; 0.5% (2/413) vs. 0.3% (3/934), P>0.05). The coincidence rate of LAAO indication was 81.3% (130/160), and the rate was higher in center performing ≥20 cases than in centers performing<20 cases (84.8% (106/125) vs. 68.6% (24/35), P<0.05). The complication and severe complication rates of LAAO were 3.1% (5/160) and 1.9% (3/160). The rate of complications in LAAO was higher in center performing<20 cases than in centers performing ≥20 cases (8.6% (3/35) vs. 1.6% (2/125), P<0.05), and there was no significant difference in severe complication rate (5.7% (2/35) vs. 0.8% (1/125), P>0.05). Conclusions: Interventional therapy for AF in China is generally standardized and safe. The overall incidence of complications post AF interventional ablation is low, the anticoagulation rate after AF catheter ablation is high, and the adherence rate of LAAO indication is fair. The indicators mentioned above vary widely among centers.

Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway / 中国天然药物

Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg

The Expression and Significance of Serum Protein ROCK2 in Patients with Chronic Graft-Versus-Host Disease / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT.@*RESULTS@#The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment（P＜0.01）; the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ（P＜0.01）. The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD（P＜0.05）.@*CONCLUSION@#ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.

Progress in diagnosis of sepsis-associated acute kidney injury in children / 中国小儿急救医学

Acute kidney injury(AKI)is a very common critical disease worldwide, especially in pediatric intensive care unit(PICU). There are many pathogenic factors for AKI, among which sepsis is essential to the development of AKI.Sepsis-associated acute kidney injury(SA-AKI) often have sudden onset and poor prognosis.Because there is still a lack of powerful diagnostic tools, resulting in clinical intervention in SA-AKI often lags behind.Therefore, awareness of SA-AKI risk and early identification of injury severity, as well as timely initiation of supportive treatment, remain the main contents of current research.There are hundreds of new biological markers and diagnostic tools for early identification and prognosis of AKI.This review introduced the progress on diagnosis of SA-AKI.The aim is to improve clinicians′ understanding of SA-AKI.