The pathogenesis of hyperlipidemic acute pancreatitis caused by pancreatic duct hypertension / 临床肝胆病杂志

Compared with acute pancreatitis caused by other factors， hyperlipidemic acute pancreatitis often has a higher rate of severe conditions， greater difficulties in predicting prognosis， and a more complex and unclear pathogenesis. At present， the pathogenesis of hyperlipidemic acute pancreatitis may be associated with the elevation of serum free fatty acids， but the lipid-lowering treatment regimens do not reduce the incidence rate of this disease. Recent studies have further confirmed that pancreatic duct hypertension is an important pathogenesis of acute pancreatitis. The latest research advances have shown that hyperlipidemia can lead to pancreatic duct obstruction by causing pancreatic duct hyperplasia， forming protein embolism at the biliary-pancreatic junction， and damaging the secretory function of the pancreatic duct， while pancreatic duct obstruction can in turn cause pancreatic duct obstruction. This article reviews the latest research advances in hyperlipidemia in causing pancreatic duct obstruction and emphasizes that pancreatic duct hypertension is one of the important pathogeneses of hyperlipidemic acute pancreatitis， which will provide new ideas for exploring the pathogenesis of hyperlipidemic acute pancreatitis.

Review of evaluation and influencing factors of oral drug absorption fraction / 药学学报

Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions, etc. Internal causes include age, sex, disease, etc. This paper analyzes and systematically combs how independent variables and covariates directly or indirectly affect the three time-related factors by affecting the body's physiology and internal environment, thus changing the complex process of Fa. Understanding this theoretical framework can better optimize the independent variables to reduce the impact of covariates on Fa. In addition, this paper also introduces the latest progress of prediction and evaluation of Fa, including the progress of complex dissolution device and the status of software prediction.

Risk prediction of acute kidney injury in paraquat poisoning patients / 中华急诊医学杂志

Objective:To establish a risk prediction model of acute kidney injury in paraquat (PQ) poisoning patients.Methods:A retrospective observational cohort of adult patients with acute PQ poisoning between September 10, 2010 and January 16, 2020 from the Emergency Department of West China Hospital, Sichuan University were conducted. Data on demographics, clinical records, and laboratory results were collected from electronic medical record. The patients were divided into the AKI group and the non-AKI group according to whether AKI occurred during hospitalization. The patients were randomly divided into the training and validation groups (7:3). Multivariate logistic regression analysis was used to screen the independent risk factors of AKI and the nomogram was used to establish a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the differentiation and calibration of the prediction model. Decision curve analysis (DCA) was used to evaluate the clinical validity of the prediction model.Results:A total of 718 patients were included in this study. AKI occurred in 323 (45%) patients in hospital and 378 (52.6%) patients died. The mortality rate of the AKI group was higher than that of the non-AKI group (72.8% vs. 36.2%, P < 0.05). Multivariate logistic regression analysis showed that the time from poisoning to treatment ( OR=1.018, 95% CI:1.006-1.030), white blood cell count ( OR=1.128, 95% CI: 1.084-1.173), aspartate aminotransferase ( OR=1.017, 95% CI:1.006-1.027), cystatin C ( OR=516.753, 95% CI: 99.337-2688.172), and PQ concentration ( OR=1.064, 95% CI:1.044-1.085) in blood on admission were independent risk factors of AKI in patients with PQ poisoning ( P<0.01). The area under the ROC curve was 0.943 (95% CI: 0.923-0.962) in the training cohort, and the sensitivity and specificity were 82.4% and 93.6%, respectively. The calibration curve showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusions:The time from poisoning to treatment, white blood cell count, aspartate aminotransferase, cystatin C, and PQ concentration in blood on admission were independent risk factors of AKI. The predictive model based on the above indicators has high sensitivity and specificity in evaluating AKI after PQ poisoning. Whether this prediction model can be applied to other PQ poisoning patients needs to be further expanded for verification.

Mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma cells / 国际肿瘤学杂志

Objective:To investigate the inhibitory effect and killing mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma (NK/TCL) .Methods:Human NK cell leukemia cell line YT and human NK/TCL cell line NK92 cells were treated with 0, 0.05, 0.10, 0.20, 0.30, 0.40, 0.50 μmol/L BDA-366. CCK-8 assay was used to calculate the half inhibitory concentration (IC 50) value of BDA-366 on these cells. The apoptosis levels of cells in control group and IC 50 BDA-366 treated group were detected by flow cytometry. Western blotting was used to detect the expression levels of apoptosis-related proteins in cells of control group and 1/2 IC 50, IC 50, 2× IC 50 BDA-366 treated groups. TMRE and Fluo-3 fluorescent probe were used to detect mitochondrial membrane potential of control group and IC 50 BDA-366 treated group, and the intracellular Ca 2+ concentration of control group, IC 50, 2× IC 50 BDA-366 treated groups. NOD-SCID mice in control group and 10 mg/kg BDA-366 intraperitoneal injection group were weighed and HE staining was performed to evaluate the toxicity of BDA-366 in vivo. Results:The IC 50 of BDA-366 for YT and NK92 cells were 0.065 and 0.086 μmol/L respectively. The apoptosis rates of YT cells in the control group and 0.065 μmol/L BDA-366 group were (6.62±1.59) % and (34.60±3.06) % respectively. The apoptosis rates of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were (5.57±0.88) % and (29.18±0.90) % respectively, both with statistically significant differences ( t=14.05, P<0.001; t=32.58, P<0.001). The relative expression of Bax in NK92 cells of the control group, 0.043, 0.086 and 0.172 μmol/L BDA-366 groups were 0.85±0.00, 1.26±0.04, 1.51±0.18, 1.15±0.10 ( F=20.70, P<0.001), the relative expression of Bax in BDA-366 groups were higher than that in the control group (all P<0.05). The fluorescence intensity of TMRE of YT cells in the control group and 0.065 μmol/L BDA-366 group were 8 372.00±330.47 and 6 419.67±311.34, and that of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were 9 169.00±535.72 and 7 311.67±295.52 respectively, and there were statistically significant differences ( t=7.45, P=0.002; t=5.26, P=0.006). In YT cells, the intracellular Ca 2+ concentrations of 0.065 and 0.130 μmol/L BDA-366 groups were significantly higher than that of the control group (5 791.67±220.45, 6 729.33±585.39, 4 874.67±112.61, F=19.16, P=0.003) ( P=0.039; P=0.002). In NK92 cells, the intracellular Ca 2+ concentrations of 0.086 and 0.172 μmol/L BDA-366 groups were significantly higher than that of the control group (4 553.67±17.62, 4 740.33±254.50, 4 185.67±17.67, F=10.96, P=0.010) ( P=0.039; P=0.007). There was no statistically significant difference in body weight change on day 12 compared with day 0 of NOD-SCID mice between BDA-366 group and control group [ (3.18±0.01) g vs. (2.73±0.58) g, t=0.60, P=0.570], and HE staining showed no abnormal morphology of heart, liver, spleen, lung and kidney in BDA-366 group. Conclusion:BDA-366 promotes NK/TCL cells apoptosis in vitro, but does not cause weight loss and morphological changes of organs by HE staining in vivo. The inhibitory effect of BDA-366 on NK/TCL cells may be achieved by increasing Bax expression, inducing Ca 2+ release and reducing mitochondrial membrane potential.

A preliminary study on salivary microbiota of patients with laryngopharyngeal reflux / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.

Membrane anatomy-based splenic hilar lymph node dissection for gastric cancer / 中华胃肠外科杂志

There is a consensus that selectively perform splenic lymph node dissection is necessary for high-risk patients with proximal gastric cancer to achieve radical treatment. However, there are still some outstanding issues that need to be solved during the practice of splenic lymph node dissection. These include poorly defined boundaries, technical difficulties, and blurred boundaries in No. 10 and No. 11 lymph nodes, etc. Membrane anatomy has achieved successful applications in the field of gastric and colorectal surgery in recent years. The study of membrane anatomy in the splenic hilum region is controversial due to the special location of the splenic hilum, which involves multiple organs and affiliated mesentery undergoing complex rotation, folding, and fusion during embryonic development. In this manuscript, we summarize the following points based on existing research and personal experience regarding membrane anatomy. 1. There is a membrane anatomical structure that can be used for lymph node dissection in the splenic hilum region. 2. The membrane structure in the splenic hilum region can be divided into two layers: the superficial layer is composed of the dorsal mesogastrium, and the deep layer is composed of Gerota fascia, the tail of the pancreas, and the mesentery of the transverse colon (from head to tail). 3. There is a loose space between the two layers that can be used for separation during surgery. The resection of the dorsal mesogastrium belongs to D2 dissection. The No. 10 lymph node in the deeper layer belongs to the duodenal mesentery, and the resection of the No.10 lymph node exceeds D2 dissection. The complete excision of the gastric dorsal mesentery is consistent with the D2+CME surgical mode proposed by Gong Jianping's group.

Combined effect of PNPLA3 rs738409 and UGT1A1 rs10929303 gene polymorphisms on nonalcoholic fatty liver disease in children / 中华肝脏病杂志

Objective: To investigate the combined effects of patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 (C > G) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) rs10929303 (C > T) on nonalcoholic fatty liver disease (NAFLD) in children and adolescents so as to provide scientific evidence for NAFLD genetic research. Methods: 1 027 children and adolescents aged 7-18 were selected as the research subjects. The general situation, past medical history, height and body weight measurements, and B- mode ultrasound test of the liver were investigated by dedicated full-time personnel. In addition, the morning fasting venous blood was collected to measure the blood biochemical indicators. DNA was extracted and genotyped for PNPLA3 rs738409 and UGT1A1 rs10929303. Logistic regression analysis was used to analyze the association and combined effect of the two gene polymorphisms and NAFLD. Statistical analysis was performed by t-test, Mann-Whitney U test, or c2 test according to different data. Results: The GG genotype of PNPLA3 rs738409 and the CC genotype of UGT1A1 rs10929303 were associated with an increased risk of developing NAFLD in children by 89% (OR = 1.89, 95% CI: 1.11-3.23, P = 0.019) and 96% (OR = 1.96, 95% CI: 1.21-3.17, P = 0.006), respectively, while the concurrent risk of NAFLD in those who carried the above two genotypes increased by 306% compared with those who did not carry both genotypes (OR = 4.06, 95% CI: 1.90 ~ 8.66, P < 0.001). Conclusion: The combined effect of PNPLA3 and UGT1A1 gene polymorphisms can significantly increase the risk of NAFLD in children, providing new evidence for elucidating the genetic susceptibility to NAFLD.

Relationship between cadmium exposure and pulmonary function level and chronic obstructive pulmonary disease / 中华劳动卫生职业病杂志

Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.

The predictive value of warning scores for intensive care unit admission in coronavirus disease 2019 patients / 中华内科杂志

To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.

Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma: an analysis of 127 cases / 中华病理学杂志

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.

Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta / 中华妇产科杂志

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.

Progress in research of influenza vaccination in pregnant women / 中华流行病学杂志

Influenza is an acute respiratory infectious disease caused by influenza virus. Pregnancy is associated with physiologic and immunological changes that may increase the risk for influenza virus infection and influenza-related complications. Influenza vaccination is the most effective way to prevent influenza virus infection. WHO and many countries have classified pregnant women as a priority population for influenza vaccination, however, there are still many challenges for promoting influenza vaccination in pregnant women in China, influenza vaccination coverage in pregnant women remains low and some influenza vaccine package inserts list pregnancy as an absolute contraindication. In this paper, we summarize the research progress in the effects of influenza infection and influenza vaccination during pregnancy both at home and abroad, then discuss the strategies to promote influenza vaccination in pregnancy for the purpose of providing reference for the related research and policy development in China.

Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021 / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos / 中华预防医学杂志

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.

Research Progress on the Role of Tumor-Associated Macrophages in Multiple Myeloma --Review / 中国实验血液学杂志

Bone marrow microenvironment is a highly complex environment surrounding tumor, which plays an important role in the survival, proliferation, drug resistance and migration of multiple myeloma (MM) cells. As an important cellular component in tumor microenvironment, tumor-associated macrophages(TAM) has attracted attention due to its key role in tumor progression and drug resistance. Targeting TAM has shown potential therapeutic value in cancer treatment. In order to clarify the role of macrophages in MM progression, it is necessary to understand the differentiation of TAM and its characteristics of promoting MM. This paper reviews the research progress on how TAM is programmed in MM and the mechanism of TAM promoting tumor development and drug resistance.

The Distribution and Significance of Activated T Cells and Lymphocyte Subsets in Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution of bone marrow lymphocyte subsets in patients with myelodysplastic syndrome(MDS),the proportion of activated T cells with immunophenotype CD3+HLA-DR+ in the lymphocytes and its clinical significance, and to understand the effects of different types of MDS, different immunophenotypes, and different expression levels of WT1 on the proportion of lymphocyte subsets and activated T cells.@*METHODS@#The immunophenotypes of 96 MDS patients, the subsets of bone marrow lymphocytes and activated T cells were detected by flow cytometry. The relative expression of WT1 was detected by real-time fluorescent quantitative PCR, and the first induced remission rate (CR1) was calculated, the differences of lymphocyte subsets and activated T cells in MDS patients with different immunophenotype, different WT1 expression, and different course of disease were analyzed.@*RESULTS@#The percentage of CD4+T lymphocyte in MDS-EB-2, IPSS high-risk, CD34+ cells >10%, and patients with CD34+CD7+ cell population and WT1 gene overexpression at intial diagnosis decreased significantly (P<0.05), and the percentage of NK cells and activated T cells increased significantly (P<0.05), but there was no significant difference in the ratio of B lymphocytes. Compared with the normal control group, the percentage of NK cells and activated T cells in IPSS-intermediate-2 group was significantly higher(P<0.05), but there was no significant difference in the percentage of CD3+T, CD4+T lymphocytes. The percentage of CD4+T cells in patients with complete remission after the first chemotherapy was significantly higher than in patients with incomplete remission(P<0.05), and the percentage of NK cells and activated T cells was significantly lower than that in patients with incomplete remission (P<0.05).@*CONCLUSION@#In MDS patients, the proportion of CD3+T and CD4+T lymphocytes decreased, and the proportion of activated T cells increased, indicating that the differentiation type of MDS is more primitive and the prognosis is worse.

Clinical application of plasma exchange combined with continuous veno-venous hemofiltration dialysis in children with refractory Kawasaki disease shock syndrome / 中国当代儿科杂志

OBJECTIVES@#To study the role of plasma exchange combined with continuous blood purification in the treatment of refractory Kawasaki disease shock syndrome (KDSS).@*METHODS@#A total of 35 children with KDSS who were hospitalized in the Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, from January 2019 to August 2022 were included as subjects. According to whether plasma exchange combined with continuous veno-venous hemofiltration dialysis was performed, they were divided into a purification group with 12 patients and a conventional group with 23 patients. The two groups were compared in terms of clinical data, laboratory markers, and prognosis.@*RESULTS@#Compared with the conventional group, the purification group had significantly shorter time to recovery from shock and length of hospital stay in the pediatric intensive care unit, as well as a significantly lower number of organs involved during the course of the disease (P<0.05). After treatment, the purification group had significant reductions in the levels of interleukin-6, tumor necrosis factor-α, heparin-binding protein, and brain natriuretic peptide (P<0.05), while the conventional group had significant increases in these indices after treatment (P<0.05). After treatment, the children in the purification group tended to have reductions in stroke volume variation, thoracic fluid content, and systemic vascular resistance and an increase in cardiac output over the time of treatment.@*CONCLUSIONS@#Plasma exchange combined with continuous veno-venous hemofiltration dialysis for the treatment of KDSS can alleviate inflammation, maintain fluid balance inside and outside blood vessels, and shorten the course of disease, the duration of shock and the length of hospital stay in the pediatric intensive care unit.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis / 亚洲男科学杂志(英文版)

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.