Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Comparison of the myopia control effects of orthokeratology lens and peripheral defocus spectacles / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P<0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth <0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P>0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P<0.05), but there was no significant difference among different diopters(P>0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.

7,8-dihydroxy-9,10-epoxybenzoapyrene induced ferroptosis in mouse hippocampal neuron HT22 cells and its mechanism / 环境与职业医学

Background Benzo[a]pyrene (BaP) has neurotoxicity, which can induce the loss of hippocampal neurons in humans and animals and lead to spatial learning and memory dysfunction, but its mechanism is still unclear. Objective To observe the ferroptosis of mouse hippocampal neuron HT22 cells induced by 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), an active metabolite of BaP, and to explore its potential mechanism, so as to provide a basis for the study of BaP neurotoxicity mechanism. Method Mouse hippocampal neuron HT22 cells were selected and divided into four groups: solvent control group and low, medium, and high concentration BPDE exposure groups (0.25, 0.50, and 0.75 μmol·L−1). Cell survival was detected by CCK8 method. Cell morphology and ultrastructure were observed under light and electron microscopes. The levels of reactive oxygen species (ROS) and Fe2+ were detected by fluorescence probe method. Iron, 4-hydroxynonenoic acid (4-HNE), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels were detected with commercial kits. The expression levels of acyl-CoA synthase long chain family member 4 (ACSL4), cyclooxygenase 2 (COX2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were detected by Western blotting. After interventions with ferroptosis inhibitors 20 μmol·L−1 deferoxamine (DFO) and 10 μmol·L−1 ethyl 3-amino-4-cyclohexylaminobenzoate (Fer-1), the cell survival rate of each BPDE exposure group and the changes of the ferroptosis characteristic indicators and protein expression levels were observed. Results With the increase of BPDE concentration, the survival rate of HT22 cells decreased gradually, and the survival rate of each BPDE group was significantly lower than that of the solvent control group (P<0.01). Under light microscope, the number of cells in the high concentration BPDE group was significantly reduced, and atrophic cells and reduced synapses were recorded. Under electron microscope, the HT22 cells in the high concentration BPDE group showed mitochondrial shrinkage, decreased crista, and increased mitochondrial membrane density. Compared with the solvent control group, the levels of intracellular lipid ROS, Fe2+, 4-HNE, and MDA significantly increased in the high concentration group (P<0.01), the GSH and GSH-PX levels were significantly decreased (P<0.01), the protein expression levels of ASCL4 and COX2 were significantly increased (P<0.01), and the protein expression levels of SCL7A11 and GPX4 were significantly decreased (P<0.01). The ferroptosis inhibitors DFO and Fer-1 significantly reversed the cell survival rate (P<0.01), the ferroptosis characteristic indicators (ROS, Fe2+, 4-HNE, MDA, GSH, and GSH-PX levels) (P<0.01), and the expression levels of ferroptosis-related proteins (ACSL4, COX2, SLC7A11, and GPX4) (P<0.01) in the high concentration BPDE group. Conclusion BPDE can induce ferroptosis in mouse hippocampal neuron HT22 cells, which may be related to the inhibition of SLC7A11/GSH/GPX4 axis and the induction of iron metabolism disorder.

Increasing the rate of timely completion of a rapid frozen-section pathological report using the PDCA cycle / 中国基层医药

Objective:To investigate the application value of the PDCA cycle in increasing the rate of timely completion of a rapid frozen-section pathological report.Methods:The basic data of 1 926 rapid frozen section pathological reports not managed by the PDCA cycle in the Department of Pathology, Zhoushan Hospital, during January to August 2019 were collected. The number of pathological reports completed within 30 minutes and the rate of timely completion of pathological reports were calculated and compared with those calculated based on 1 051 pathological reports managed by the PDCA cycle during September to December 2019.Results:After management by the PDCA cycle, the rate of timely completion of frozen-section pathological reports was significantly increased from (84.51 ± 3.61)% to (91.87 ± 1.37)% ( t = 3.86, P < 0.05). Conclusion:Application of the PDCA cycle to pathology management can help monitor the completion of pathological reports on frozen sections. This facilitates determination of reasonable intervention measures and thereby increases the rate of timely completion of pathological reports on frozen sections.

Investigation on the IGF-1 and lipid level in term small for gestational age infants within 24 hours postnatally / 中国新生儿科杂志

Objective:To study the insulin-like growth factors-1 (IGF-1) and lipid level of term small for gestational age (SGA) infants within 24 hours postnatally and to explore the correlation between IGF-1 and blood lipids.Methods:A prospective study was conducted on singleton term SGA and appropriate for gestational age infant (AGA) who were delivered and admitted to the neonatal ward of Guangdong Women and Children Hospital within 24 hours after birth from May 2020 to January 2021, and the infants were divided into SGA and AGA groups to compare the differences in IGF-1 and lipid levels within 24 hours after birth and to analyze the correlation between IGF-1 and lipids.Results:A total of 95 cases in the SGA group and 84 cases in the AGA group were included in the study. The proportion of infants with IGF-1 <25 ng/ml was significantly higher in SGA group (87.4%) than in the AGA group (52.4%). It was also found that the proportion of infants with IGF-1 <25 ng/ml in SGA was significantly higher than that in AGA within different gender composition groups, early-term and full-term births groups. The triglyceride (TG) level was higher in the SGA group than that in the AGA group, but the high-density lipoprotein cholesterol (HDL-C) level was lower than that in the AGA group ( P<0.05). IGF-1 level within 24 hours postnatally in SGA and AGA was positively correlated with HDL-C levels ( P<0.01) and negatively correlated with TG ( P<0.01), and HDL-C level was a predictor of IGF-1. Conclusions:Compared with term AGA, SGA term infants showed insufficient IGF-1 and HDL-C secretion and high TG within 24 hours after birth. Nutritional support for SGA should be given promptly after birth to avoid hypoglycemia and to stimulate IGF-1 secretion.

Clinical and molecular characteristics of Streptococcus pneumoniae-associated hemophagocytic lymphohistiocytosis in children / 中华儿科杂志

Objective: To summarize the clinical features of Streptococcus pneumoniae-associated hemophagocytic syndrome (SP-HLH), and the serotypes and drug-resistant characteristics of the isolated strains. Methods: There were 15 children with SP-HLH admitted to the Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital, Capital Medical University from January 2013 to December 2020 were included in this study. Clinical data including children's general characteristics, clinical features, laboratory examinations, treatments, prognosis and the outcomes of follow-up by May 2021 were analyzed retrospectively. The serotypes and drug resistance of the isolated strains were identified. All children were divided into the clinical improvement group and the death group. Mann-Whitney U test, Fisher's exact test were used to compare the data of the two groups. Results: Among the 15 children with SP-HLH, 8 were males and 7 were females. The age of these children was 1.0 (1.0, 2.5) years. Regarding the primary infection, there were 9 cases of severe pneumonia, 3 cases of meningitis and 3 cases of blood stream infection. None of these children had received pneumoniae conjugate vaccine (PCV) and all of them were admitted to the PICU. Respiratory failure was observed in 10 patients, acute renal injury in 5, and hemolytic uremic syndrome in 3 patients. All children received glucocorticoids and high-dose intravenous immunogloblin (IVIG) in addition to anti-infective treatment. Eight of the children were cured while the other 7 died. The neutrophil count in the death group was lower than that in the clinical improvement group ((5.0 (1.7, 9.3) × 109 vs. 5.2 (3.4, 10.5) ×109/L, Z =-2.43, P<0.015), and the length of hospital stay and days of PICU stay in the death group were both shorter than those in the improvement group statistically (3 (1, 11) vs. 39 (34, 48) d, 2 (1, 4) vs. 19 (12, 31) d, Z=-3.25, -3.24, both P=0.001). Ten serotypes of Streptococcus pneumoniae were identified, including 4 strains of 19F, 3 of 19A, 1 of 23F, 1 of 15A and 1 of 14, among which 9 strains (9/10) were covered by PCV13. All strains were resistant to erythromycin yet sensitive to vancomycin and linezolid. Conclusions: SP-HLH is more common in children under the age of 3, with a high mortality rate. The death cases have lower neutrophil count and rapid disease progression. The comprehensive treatment is anti-infective combined with glucocorticoids and high-dose IVIG. The predominant serotypes are 19F and 19A and all isolated strains were susceptible to vancomycin and linezolid.

Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head / 中华外科杂志

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

Two-dimensional ultrasound combined with HD-live silhouette technology in embryos/fetuses with normal or abnormal central nervous system during early pregnancy / 中华围产医学杂志

Objective:To study the ultrasonographic characteristics of embryos/fetuses with normal or abnormal central nervous system (CNS) from 7 to 13 +6 weeks of gestation using high resolution two-dimensional ultrasound combined with HD-live silhouette technology and provide a reference for early diagnosis of CNS abnormalities. Methods:Eighty normal embryos/fetuses during 7-13 +6 weeks and 41 fetuses with CNS malformations in early pregnancy during 11-13 +6 weeks were selected to observe the ultrasonographic features of embryos/fetuses with normal or abnormal CNS using transvaginal high resolution two-dimensional ultrasound and HD-live silhouette technology. Descriptive analysis was performed on the results. Results:From seven weeks of gestational age, high resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically show the prosencephalon, mesencephalon and rhombencephalon. The rhombencephalon changed the most in the brain development of embryos. At nine weeks of gestation, cleared structures of pons curvature, the fourth ventricle and cisterna magna were observed. The developing cerebellum and the original Blake pouch cyst were seen at 10 weeks of gestation. From 11 to 13 +6 weeks, the most remarkable change was the choroid plexus of the fourth ventricle changed from perpendicular to parallel to the long axis of the neural tube. Of the 41 fetuses with CNS malformation, 16 (39.0%) were exencephaly, 11 (26.8%) were holoprosencephaly, five (12.2%) were encephalocele, four (9.7%) were anencephaly, three (7.3%) were fourth ventricle dilatation, and two (4.9%) were open spina bifida. Conclusions:High resolution two-dimensional ultrasound combined with HD-live silhouette technology can clearly and stereoscopically display the morphological changes in embryonic embryos/fetuses with development of normal CNS at 7-13 +6 weeks, which is helpful to better understand the origin of CNS embryonic abnormalities and provide diagnostic clues for the early detection of CNS abnormalities.

Effect of short-term high protein and low carbohydrate diet interventions in patients with obesity and hypertension / 中华健康管理学杂志

Objective:To determine the effect of short-term high protein and low carbohydrate diet interventions on weight-related metabolic indexes in obese patients with hypertension.Methods:A retrospective study was conducted on 200 obese patients with hypertension who underwent physical examination and weight management in Shenzhen People′s Hospital from May 2015 to December 2019. Among them, 100 patients were given routine diet education (control group), and 100 patients were given high protein and low carbohydrate diet interventions (experimental group). After eight weeks, changes in body weight, body mass index, blood pressure, fasting blood glucose, blood lipid, and medical expenses were compared. T-test and Wilcoxon rank sum test were used to compare the differences between the two groups before and after the interventions. When P<0.05, it was considered significantly different. Results:After the intervention, body weight, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglycerides, and medical expenses of the experimental group decreased [79.0 (74.0, 85.0) vs 70.0 (66.0, 72.0) kg; 28.5 (26.8, 29.5) vs 26.1 (25.4, 27.7) kg/m 2; 168.0 (162.0, 178.0) vs 160.0 (154.0, 166.0) mmHg(1 mmHg=0.133 kPa); 101.0 (98.0, 108.0) vs 97.0 (90.5, 98.0) mmHg; 5.25 (4.80, 5.52) vs 4.95 (4.70, 5.20) mmol/L; 5.80 (5.27, 6.40) vs 5.40 (5.00, 5.80) mmol/L; 1.25 (0.90, 1.50) vs 1.10 (0.90, 1.20) mmol/L;(669.6±21.6) vs (646.4±21.3) CNY, respectively] (all P<0.05). The body weight of the control group decreased [78.0(73.3, 83.0) vs 79.5(74.5, 85.0) kg] ( P<0.05). The control group′s body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglycerides, and medical expenses had no significant changes (all P>0.05). Conclusion:Short-term, high protein, low carbohydrate diet intervention can effectively reduce weight, hypertension, fasting blood glucose, total cholesterol, triglycerides, and medical expenses in obese patients with hypertension.

Pathogenesis and prognosis of tumor-induced acute pancreatitis: An analysis of 84 cases / 临床肝胆病杂志

Objective To investigate the association of biliary, pancreatic, and ampullary tumors with the onset of acute pancreatitis (AP) and the clinical features of tumor-induced AP by retrospectively analyzing the clinical data of patients with tumor-induced AP. Methods Related clinical data were collected from the patients with AP who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021. The etiological composition of AP was analyzed, as well as the change in the incidence rate of tumor-induced AP; the clinical features of AP were compared between tumor-induced and non-tumor-induced AP and between the tumors at different locations to explore the pathogenesis of tumor-induced AP. For normally distributed continuous data, the t -test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK- q test was used for further comparison between two groups. For non-normally distributed continuous data, the Mann-Whitney U test was used for comparison between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank-sum test was used for further comparison between two groups. The chi-square test or the Fisher's exact test was used for comparison of dichotomous categorical data between groups, and the goodness-of-fit test was used for comparison of polytomous categorical data between groups. The receiver operating characteristic (ROC) curve was used to evaluate the differential factors for pancreatic tumor-induced AP, and a multivariate logistic regression analysis was used to investigate the independent predictive factors for tumor-induced AP. Results A total of 8106 patients with AP were enrolled, among whom 84 patients (1.04%) had tumor-induced AP (tumor group). The tumor group had a significantly higher mean age than the non-tumor group ( t =6.050, P < 0.001). The mean time from initial onset of AP to tumor diagnosis was 7.38 months. Among the 84 patients with tumor-induced AP, 75 (89.2%) had mild AP (MAP), 8 (9.5%) had moderate severe AP, and 1(1.2%) had severe AP; as for the origin of tumor, 11(13.1%) had tumor originating from the lower biliary tract, 13(15.5%) had tumor originating from the ampulla, and 60(71.4%) had tumor originating from the pancreas. Recurrence of AP (risk ratio [ RR ]=8.362, 95% confidence interval [ CI ]: 3.162-22.115, P < 0.001), pancreatic duct dilatation ( RR =10.996, 95% CI : 3.871-31.236, P < 0.001), bile duct dilatation ( RR =7.738, 95% CI : 2.521-23.752, P < 0.001), and leukocyte count ( RR =0.766, 95% CI : 0.666-0.881, P < 0.001) were independent predictive factors for tumor-induced AP. Conclusion Tumor-induced AP is common in middle-aged and elderly men, with the clinical manifestations of MAP, easy recurrence, pancreatic duct dilatation/bile duct dilatation, and a persistent increase in the tumor marker CA19-9. Imaging examination of the biliary, pancreatic, and ampullary regions should be enhanced for AP with the above characteristics and no apparent trigger, and follow-up should be strengthened to avoid the missed diagnosis of tumor and the influence on prognosis.

Characteristics of Traditional Chinese Medicine Syndromes and Treatments of COVID-19 Patients from Two Hospitals Based on “Treatment of Disease in Accordance with Three Conditions” / 中国实验方剂学杂志

ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019（COVID-19） based on the differences of syndromes and traditional Chinese medicine（TCM） treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system （HIS） of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai，dominated by young and middle-aged males，had clinical symptoms of fever， abnormal sweating，and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat， with manifest cold， dampness， and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness， accompanied by draining depressed heat. The core Chinese medicines used are Poria，Armeniacae Semen Amarum，Gypsum Fibrosum，Citri Reticulatae Pericarpium，and Pogostemonis Herba. By contrast，the 105 patients in Ruili， dominated by young females， had atypical clinical symptoms， and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach， with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen， resolving dampness， and dispersing Qi with light drugs. The core Chinese medicines used are Poria，Atractylodis Macrocephalae Rhizoma，Glycyrrhizae Radix et Rhizoma，Coicis Semen，Platycodonis Radix，Lonicerae Japonicae Flos， and Pogostemonis Herba. ConclusionThe differences in clinical characteristics， TCM syndromes， and medication of COVID-19 patients from the two places may result from different regions，population characteristics， and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.

Total Flavones of Spatholobi Caulis Regulate Hippocampal Neuroplasticity in Depressed Rats Through CREB/BDNF Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total flavones of Spatholobi Caulis （TFSC） against depression in rats. MethodThe fifty KM mice were randomly divided into the normal group and high-， medium-， and low-dose （1， 0.5， 0.25 g·kg-1） TFSC groups and gavaged with the corresponding drugs for 12 successive days. One hour after the last administration， the immobility time in forced swimming test and tail suspension test was recorded. The SD rats were randomly divided into the normal group， model group， fluoxetine （5 mg·kg-1） group， and high- and low-dose （1， 0.25 g·kg-1） TFSC groups. Following the exposure of rats to two different kinds of stimuli daily for inducing chronic unpredictable stress， they were administered with the corresponding drugs for 21 d. After the experiment， the levels of serum neurotransmitters and inflammatory factors in rats were detected by enzyme-linked immunosorbent assay （ELISA）. The changes in hippocampal neurons of rats were observed by hematoxylin-eosin （HE） and Nissl staining. The mRNA expression levels of nuclear factor-κB （NF-κB） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of cAMP-response element binding protein （CREB）， phosphorylated CREB （p-CREB）， and brain-derived neurotrophic factor （BDNF） in hippocampal tissues by Western blot. ResultCompared with the normal group， TFSC significantly shortened the immobility time of mice in tail suspension and swimming tests （P<0.05）. Compared with the normal group， the model group exhibited reduced sucrose intake and wilderness activity （P<0.01）， decreased 5-HT， DA， NE （P<0.05， P<0.01）， MAO， IL-6， TNF-α （P<0.05， P<0.01）， damaged neurons， increased mRNA levels of TNF-α and NF-κB （P<0.01）， and down-regulated BDNF and CREB protein expression （P<0.05）. Compared with the model group， TFSC significantly enhanced sucrose intake and wilderness activity of rats （P<0.05）， increased the serum 5-HT， DA and NE （P<0.05， P<0.01）， and decreased the serum MAO， IL-6， and TNF-α （P<0.05， P<0.01） as well as NF-κB and TNF-α mRNA expression （P<0.01）， up-regulated the protein expression levels of BDNF and CREB （P<0.01）， and improved the pathological symptoms of hippocampus. ConclusionTFSC improved the hippocampal neurons of rats via CREB/BDNF signaling pathway and reduced depressive pathological damage， thus relieving depression.

An Intronic Variant of CHD7 Identified in Autism Patients Interferes with Neuronal Differentiation and Development / 神经科学通报·英文版

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.

Deep Learning-Based Cardiac Imaging Data Measurement and Its Application in Diagnosis of Sudden Cardiac Death / 法医学杂志

In the field of forensic medicine, diagnosis of sudden cardiac death is limited by subjective factors and manual measurement methods, so some parameters may have estimation deviation or measurement deviation. As postmortem CT imaging plays a more and more important role in the appraisal of cause of death and cardiopathology research, the application of deep learning such as artificial intelligence technology to analyze vast amounts of cardiac imaging data has provided a possibility for forensic identification and scientific research workers to conduct precise diagnosis and quantitative analysis of cardiac diseases. This article summarizes the main researches on deep learning in the field of cardiac imaging in recent years, and proposes a feasible development direction for the application of deep learning in the virtual anatomy of sudden cardiac death at present.

Evaluation of quantitative stool occult blood test in opportunistic screening for colorectal cancer / 中华健康管理学杂志

Objective:To evaluate the efficacy of quantitative fecal immunochemical test (fecal immunochemical test, FIT) in the screening of colorectal cancer and precancerous lesions.Methods:47 243 patients who underwent quantitative FIT screening for colorectal cancer in the Health Management Department of Shenzhen People′s Hospital from January 2019 to October 2020 were enrolled as subjects. Colonoscopy was recommended for patients with positive quantitative FIT. A follow-up was done after one year to compare the results of the quantitative FIT positive group and the negative group after colonoscopy. Data were adjusted by propensity score matching method and a receiver operating characteristic curve ( ROC) was established to evaluate the diagnostic effect of quantitative FIT combined with colonoscopy on colorectal cancer and precancerous lesions. Results:A hemoglobin concentration>100 μg/L was set as a positive threshold. There were 2 472 positive cases of quantitative FIT, and the positive rate was 5.23%. After one-year follow-up, 284 patients had completed colonoscopy; the colonoscopy compliance was 11.49%. Of the negative population, 1 493 patients selected colonoscopy within one year. Compared with the results of gold standard colonoscopy, the sensitivity and specificity of quantitative FIT for screening for advanced adenoma and cancer were 26.53% and 86.54%, respectively. The sensitivity for colorectal cancer screening was 94.44% and screening for advanced adenoma was 22.77%. After propensity score matching, there were 256 FIT positive patients and 705 FIT negative patients. Colorectal cancer was the outcome variable, while FIT combined with colonoscopy, age combined with colonoscopy, and FIT combined with age combined with colonoscopy were the diagnostic indicators. The areas under the curve were 0.841(95% CI:0.778-0.904), 0.677(95% CI: 0.535-0.820), and 0.882(95% CI:0.807-0.958), respectively. Conclusion:Quantitative FIT has a high susceptibility to opportunistic screening for colorectal cancer, and a low sensitivity to advanced adenoma. At the same time, quantitative FIT combined with colonoscopy has a good diagnostic accuracy for colorectal cancer, which is better than the effect of using age as a cut-off point for colonoscopy. Quantitative FIT combined with age and colonoscopy has the best effect on screening for colorectal cancer. Quantitative FIT has a high sensitivity to colorectal cancer and a low sensitivity to advanced adenoma.

Evaluation of the effect of remote lifestyle intervention on the management of weight and related indicators in the overweight and obese population / 中华健康管理学杂志

Objective:To evaluate the effect of remote lifestyle intervention on the management of weight and related indicators in the overweight and obese population.Methods:A total of 400 individuals with overweight or obesity who participated in remote lifestyle intervention in the Health Management Department of Shenzhen People′s Hospital from May 2015 to December 2018 were included as the remote intervention group, and 400 individuals with overweight and obesity who matched their age and gender were selected as the control group. Dietician established individual WeChat groups with the remote intervention group, and the WeChat platform was used to conduct remote lifestyle intervention for them, including setting weight control goals, giving timely feedback to the food log based on photos, providing exercise guidance and psychological support. The control group received personalized diet and exercise prescriptions, but did not receive remote intervention. After adjusting the data by propensity score matching method, univariate and multivariate logistic regression models were used to analyze the management effect of weight and related indicators in the two groups after one year.Results:After one year of intervention, effective data were obtained from a total of 755 cases (371 cases in the remote intervention group and 384 cases in the control group), and effective data were retained from 446 cases (223 cases in the remote intervention group and 223 cases in the control group) after bias matching. The body mass index (BMI), systolic blood pressure, fasting blood glucose, triglyceride, total cholesterol, low-density lipoprotein, and serum uric acid of the remote intervention group [(24.85±2.52) kg/m 2, (110.21±10.53) mmHg, (4.96±0.65) mmol/L, (1.25±0.82) mmol/L, (4.87±1.11) mmol/L, (2.88±0.74) mmol/L, and (306.01±95.66) mmol/L respectively] were significantly lower than that of the control group [(27.76±2.28) kg/m 2, (121.14±14.07) mmHg, (5.10±0.87) mmol/L, (1.54±0.83) mmol/L, (5.28±0.96) mmol/L, (3.13±0.80) mmol/L, (355.16±92.68) mmol/L respectively] (all P<0.05). After intervention, intervention was consistently being influencing factors when BMI was reduced by 4%―12%, ( P<0.05). The probability of a 12% reduction in BMI in the remote intervention group was 112.486 times higher than that in the control group (95% CI: 16.852-890.266). At the same time, the initial BMI was an influential factor for the restoration of normal BMI. For every 1 kg/m 2 decrease in the initial BMI, the probability of restoration of normal BMI was 4.76 times higher than that before the decrease (95% CI: 3.222-5.057). Conclusions:Remote lifestyle intervention has a certain effect on the management of weight and related indicators in the overweight and obese populations. It has significant effect on weight loss of overweight and mildly obese people, but has limited effect on moderate and severe obese people.

Clinical metabolomics research on Xiaozhang Tie with the umbilical compress therapy for cirrhotic ascites / 药学学报

We used metabolomics technology to identify and understand the biomarkers and therapeutic mechanisms of umbilical compress therapy based on Xiaozhang Tie (XT) to provide scientific evidence for its clinical application. A total of 10 patients with cirrhotic ascites and gastrointestinal motility disorders who were hospitalized in the Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2017 to June 2018 were divided into a placebo group (4 cases) or an XT group (5 cases), and 10 healthy volunteers were included as controls. This clinical trial was approved according to the Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (2017-528-11-01). The patients in the XT group were given umbilical compress therapy with Xiaozhang Tie, and patients in the placebo group were administered a plaster patch in which the drug content was less than 5%, receiving one patch per day for three consecutive days. Non-targeted metabolomics technology and UPLC-Q/Orbitrap-MS/MS analysis technology were utilized to investigate the fluctuations in endogenous metabolic profiles in the patient's urine prior to and after administration of XT. By analyzing and comparing the urine metabolic profiles of patients with cirrhotic ascites to those of healthy volunteers, a total of 31 biomarkers were identified, 14 of which were significantly decreased by the intervention with Xiaozhang Tie (P <0.05). Pathway enrichment analysis revealed that phenylalanine metabolism and tryptophan metabolism are key pathways affected by XT treatment. The results suggest that XT can alleviate cirrhotic ascites by modulating abnormalities in amino acid metabolism.

Effect of Gecko Extract on Neuroinflammation in Rats with Reserpine-induced Depression via TLR4/NF-κB Pathway / 中国实验方剂学杂志

Objective:To investigate the effects and mechanism of Gecko extract for treatment of depression in rats. Method:The depression rats were induced by intraperitoneal injection of reserpine （0.5 mg·kg^-1）. The successfully modeled rats were randomly divided into model group， fluoxetine group （1.8 mg·kg^-1）， high dose and low dose groups of Gecko extract （12， 6 g·kg^-1）. The rats were given corresponding dose of drugs once a day for 10 days. After administration， the levels of neurotransmitters and inflammatory factors in serum and prefrontal cortex of rats were detected by enzyme-linked immunosorbent assay （ELISA）. The cell changes in hippocampal tissues were observed by hematoxylin-eosin （HE） staining. The mRNA levels of interleukin-6 （IL-6）， nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， and tumor necrosis factor （TNF-<italic>α</italic>） in the hippocampus of rats were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein levels of Toll-like receptor 4 （TLR4） and NF-<italic>κ</italic>B in hippocampal tissues of rats were detected by Western blot. Result:Compared with the normal group， Gecko extract significantly shortened the immobility time of tail suspension and swimming in mice. Compared with model group， Gecko extract significantly reduced blepharoptosis and retention time in circles for the rats （<italic>P</italic><0.05）， increased the levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in serum （<italic>P</italic><0.05）， decreased the levels of Monoamine oxidase （MAO）， IL-6， and TNF-<italic>α</italic> in serum （<italic>P</italic><0.05） and prefrontal cortex （<italic>P</italic><0.05）， decreased the mRNA levels of inflammatory cytokines IL-6， NF-<italic>κ</italic>B and TNF-<italic>α</italic> and the protein expressions of TLR4 and NF-<italic>κ</italic>B in the hippocampus of rats （<italic>P</italic><0.05，<italic> P</italic><0.01）， and improved the pathological symptoms of the hippocampus. Conclusion:Gecko extract can significantly alleviate the pathological damage of depression and improve the symptoms of depression， and its mechanism may be due to inhibiting TLR4/NF-<italic>κ</italic>B signaling pathway and reducing the expression of NF-<italic>κ</italic>B， IL-6 and other inflammatory factors in the hippocampus of rats.

Clinical features and pathological types of pulmonary nodules with different components / 中国医师杂志

Objective:To investigate the clinical features, pathology and prognosis of pulmonary nodules.Methods:The data of patients with pulmonary nodules diagnosed by computed tomography (CT) in the Affiliated Hospital of Yangzhou University from 2015 to 2017 were analyzed retrospectively. The pathological results of all the nodules that were resected by video-assisted thoracoscopic surgery (VATS) were obtained definitely. Moreover, the prognosis of pulmonary nodules was also investigated by analyzing their clinical features and pathology.Results:Of all 117 pulmonary nodules, the number of pure ground glass nodules (pGGN), mixed ground glass nodules (mGGN) and solid nodules was 37, 64, and 16, respectively. Nodules of different compositions are more common in women, and are mostly located in the upper lobe of the right lung. There were significant differences in the pathological types of nodules with different components. The pathological results of pGGNs were mainly adenocarcinoma in situ (AIS) (51.4%, P<0.001), and mGGNs were also characterized by AIS (37.5%, P=0.001), while solid nodules were mainly invasive adenocarcinoma (IAC) and others ( P<0.001). Meanwhile, the diameter of solid nodules was significantly larger than that of mixed ground glass nodules and pure ground glass nodules [(17±8)mm, P<0.001], and the diameter of IAC in the mGGNs [(15±7)mm, P<0.001] and solid nodules [(22±8)mm, P=0.031] was significantly larger than other pathological types. In addition, the prevalence of complications after thoracoscopic surgery was 9.0% (10/111), and symptomatic treatment was effective after 1-3 months. Conclusions:The components and diameter of pulmonary nodules were closely related to lung adenocarcinoma. With the increase of solid components and diameter of nodules, it is possible to develop into IAC. Therefore, CT screening of pulmonary nodules is beneficial to the diagnosis and treatment for early lung cancer, and significant to the improvement of prognosis.

Pharmacogenetics progress of commonly-used chemotherapeutic drugs for acute leukemia / 白血病·淋巴瘤

Leukemia is a common and harmful disease for humans. Chemotherapy is the main treatment method. During the decades of experience, the clinicians have found that these drugs work well, but obvious individual differences occur in different patients. Some concerns of the clinicians exist such as how to learn more about the factors that may induce drug resistance and adverse reactions, and how to improve the efficacy of chemotherapy drugs, reduce drug resistance and side effects. This paper reviews the effect of genetic factors of commonly-used chemotherapeutic drugs for acute leukemia, aiming to provide a theoretical foundation for personalized administration of these chemotherapeutic drugs.