Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.
Rats ; Animals ; Berberine/pharmacokinetics* ; Tissue Distribution ; Chromatography, Liquid ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Alkaloids/pharmacokinetics* ; Chromatography, High Pressure Liquid/methods* ; Arthritis

Abstract: Objective To screen out a more universally applicable culture medium for the isolation and culturing of pathogenic fungi through comparing the performance of various universal fungal culture media, to optimize the fungal culturomics technique, and to better apply it to the culturomics research of pathogenic fungi. Methods Multiple common fungal culture media Sabouraud dextrose agar (SDA), potato dextrose agar (PDA), modified Dixon (mDixon), modified LeemingNotman agar (MLNA), etc., and a new pan-fungal medium (PF) were used to culture 40 strains of common pathogenic fungi to determine the growth states of strains under different conditions. Based on that, PF, SDA, PDA, mDixon and MLNA, a total of 5 culture media, were used to isolate and culture a simulated sample (suspension of Candida albicans and Aspergillus fumigatus), 10 human samples (4 fecal samples and 6 vaginal secretion samples) and 3 environmental samples. Results The positive growth rates of 40 strains of pathogenic fungi in the 7 media were as follows: PDA 95.0% (38/40), SDA 95.0% (38/40), BHI 95.0% (38/40), YPD 90.0% (36/40), mDixon 95.0% (38/40), MLNA 87.5% (35/40), PF 100.0% (40/40). For the simulated samples, PF could effectively promote the self-limited growth of filamentous fungi, performing better in isolation and culture. For the human samples and environmental samples, PF showed the same versatility as SDA and PDA. Conclusions In the isolation and culturing of pathogenic fungi, PF medium can effectively isolate and culture most fungal species. Meanwhile, PF can make the fast-growing fungi show self-limited growth and clear edges, and not easy to cross-contamination, which indicates it is conducive to the isolation and identification of single colonies. PF medium outperforms other common media in isolating strains from unknown samples in culturomics, which illustrates PF medium can be effectively used for the study of fungal culturomics.

Objective: To investigate the relation between nicotinic acetylcholine receptor subunit (nAChR) genes and schizophrenia, and the relation between tag single nucleotide polymorphism (rs1317286, rs1044396, rs6494212, rs16969968, and rs684513) and schizophrenia in Han Chinese people. Methods: The protein-protein interaction (PPI) network among nAChR protein and 350 proteins encoded by schizophrenia-related susceptibility genes was constructed through the String database to explore whether nAChR genes were associated with schizophrenia in these known databases. Then, five single nucleotide polymorphisms (SNPs) of CHRNA3 (rs1317286), CHRNA4 (rs1044396), CHRNA7 (rs6494212), and CHRNA5 (rs16969968, rs684513) were analyzed in a sample of 1,035 schizophrenic patients and 816 healthy controls. The interaction between the markers was analyzed using multifactor dimensionality reduction (MDR) software. Power analysis was performed using the Quanto program. Results: There are no significant differences in genotype or allele distribution were identified between the patients and controls (p>0.05). The haplotypes constructed by four markers rs1317286, rs6494212, rs16969968, and rs684513 were not associated with schizophrenia either. However, a significant association between models made of rs1317286, rs1044396, rs6494212, and rs684513 and schizophrenia was revealed in interaction analysis (p<0.05). Conclusion The nAChR protein may have effects on the development of schizophrenia through the interaction with proteins encoded by schizophrenia-related susceptibility genes, but no relation was found between selected polymorphisms and schizophrenia in the collected Han Chinese people. However, interaction analysis suggested four-SNP model has an important effect on schizophrenia.

Objective:To investigate the therapeutic effects of noninvasive ventilation on heart failure(HF)after acute myocardial infarction(AMI)in rats.Methods:A rat model of HF after AMI was established by ligation of the left ventricular branch.Thirty male Wistar rats were randomly divided into three groups according to the random number table method: sham operation group, non-treatment group and noninvasive ventilation treatment group(n=30, each group). Echocardiography was performed on the third day after surgery, and parameters including left atrial diameter(LAD), left ventricular end diastolic diameter(LVEDD), interventricular septum thickness(IVS)and left ventricular ejection fraction(LVEF)were recorded.Serum levels of brain natriuretic peptide 45(BNP45), tumor necrosis factor α(TNF-α), matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), and heat-shock protein 70(HSP70)were measured at day 3 after operation by enzyme-linked immunosorbent assays(ELISA). Morphological changes of myocardial tissue were analyzed with hematoxylin-eosin(HE)staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL).Results:Compared with the non-treatment group, LVEDD decreased[(153.9±8.1)mm/m 2vs.(164.7±10.4)mm/m 2, P<0.05]and LVEF increased[(63.9±7.6) % vs. (54.4±9.4) %, P<0.05]in the noninvasive ventilation group .Compared with the non-treatment group, serum levels of BNP45[(0.65±0.07) % vs. (0.73±0.07) μg/L, P<0.05], TNF-α(361.5±13.1) μg/L vs. (399.1±12.6) μg/L( P<0.05), MMP-2(6 892.8±530.2) μg/L vs. (7 406.0±667.5) μg/L( P<0.05)and MMP-9(143.8±5.9) μg/L vs. (151.1±8.3) μg/L( P<0.05)decreased and levels of HSP70[(1.7±0.1)μg/L vs.(1.4±0.1)μg/L, P<0.05]increased in the noninvasive ventilation group.HE staining showed focal accumulation of neutrophils in the epicardium, loss of muscle striation, disorganized cell polarity and enlarged nuclei in the non-treatment group.Meanwhile, alleviated inflammation, scattered neutrophils between cardiomyocytes and misaligned muscle striation were observed in the noninvasive ventilation group.TUNEL results showed that the myocardial apoptotic index was lower in the noninvasive ventilation group than in the non-treatment group( P<0.05). Conclusions:Noninvasive ventilation can effectively improve heart function, reduce inflammatory response and cardiomyocyte apoptosis in rats with AMI-induced HF and may be an effective treatment for HF after AMI.

Objective To study the effect of noninvasive ventilation on heart failure(HF)in rats after acute myocardial infarction(AMI)and the mechanisms involved.Methods A total of 30 Wistar rats were randomly divided into three groups:the noninvasive ventilation group,the non-treatment group and the sham operation group(n=10 in each group).The model for HF after AMI was established by left anterior descending coronary artery ligation.Serum levels of B-type natriuretic peptide-45 (BNP-45),70 000 heat-shock protein(HSP70),matrix metalloproteinases(MMP-2 and-9),tumor necrosis factor-α(TNF-α)and echocardiography parameters,such as left atrium(LA)diameter,left ventricular(LV)end-diastolic diameter,interventricular septal(IVS)thickness,and left ventricular ejection fraction(LVEF),were measured at 3,5,7 and 14 days after operation in each group.Results Compared with the non-treatment group,LVEDD was reduced and LVEF was increased in the noninvasive ventilation group at 14 days after operation(155.92±14.74)mm/m2 vs.(149.35±11.29)mm/m2,(92.13±3.72)％ vs.(76.39±9.24)％,(P＜0.05),while LA diameter and IVS thickness showed no significant difference(P＞0.05).Compared with the non-treatment group,serum levels of BNP45,MMP-2,MMP-9,and TNF-α were decreased and HSP70 levels were increased in the noninvasive ventilation group at 3,5,7,and 14 days after operation (P ＜ 0.05).In the noninvasive ventilation group,serum levels of BNP45,MMP-2,MMP-9 and TNF-α at 5,7,and 14 days after operation were lower than those at 3 days after operation,and serum HSP70 levels at 7 and 14 days after operation were higher than those at 3 days after operation (P ＜ 0.01).Conclusions Noninvasive ventilation can effectively reduce the inflammatory response in rats with HF after AMI and reduce myocardial ischemia-reperfusion injury.It is an effective treatment for HF after AMI.

Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06％ (174/207),85.71％ (168/196) and 63.11％ (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34％ (145/262),48.06％ (124/258) and 46.15％ (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6％ and 45.8％.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P＜0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95％ confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P＜0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95％ CI:0.15-0.82,P＜0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.

Objective To explore the feasibility and application in quantifying the rabbit central nervous system by using magnetic resonance diffusion tensor imaging(DTI)sequences.Methods 12 normal New Zealand rabbits were used to scan the brain and spinal cord of rabbits by DTI sequence of 1.5T MR machine,and the normal apparent diffusion coefficient(ADC)and fractional anisotropy (FA)values were obtained in the different regions of the brain and every spinal segment of rabbits,to analyse the characteristics and regularity of numerical changes.Results The average ADC value in the brain of rabbits was (0.87±0.08)×10-3mm2/s,the average FA value was 0.23±0.09;the average ADC value in cervical spinal cord was (1.05±0.14)×10-3mm2/s,the average FA value was 0.55±0.08.The average ADC value in thoracic spinal cord was (1.14±0.12)×10-3mm2/s,and the average FA value was 0.57±0.06;the average ADC value in lumber spinal cord was (1.20±0.12)×10-3mm2/s,and the average FA value was 0.61±0.06.Conclusion FA average value in the brain is lower than that in spinal cord (P<0.001),the difference is related to the distribution of nerve fibers and physiological curvature of spine.ADC average value in the brain is lower than that in spinal cord(P<0.001),this is related to the volume of spinal canal and the peripheral structure of spinal cord.The difference of FA value in the brain and spinal cord is higher than ADC value.

Objective · To investigate the effect of modified electroconvulsive therapy (MECT) on oxidative stress parameters in patients with bipolar disorder. Methods · Forty-three patients with bipolar disorder (case group) were enrolled that received MECT intervention for 6 weeks, and 49 healthy volunteers (control group) were recruited. Chinese versions of the 17 items Hamilton Depression Rating Scale (HAMD-17), Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) were used to assess the efficacy and side effects at baseline and after 6 weeks of treatment. The plasma levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured at baseline and after 6 weeks of treatment to assess the level of oxidative stress. Results · The serum MDA and GSH-Px levels of the case group were higher while the serum SOD levels of the case group was lower than that of the control group, and there was no significant difference in the serum CAT levels between two groups at baseline. MDA levels were higher in manic states than in depressed states, and they were positively correlated with the CGI-S scores. After MECT treatment, the CGI-S scores of patients decreased significantly, and the plasma MDA levels decreased significantly in manic and depressive states, but there was no change in other oxidative stress parameters. Conclusion · There was oxidative stress damage in patients with bipolar disorder, and the severity of the disease varied with the degree of damage. MECT improved the symptoms of the disease and decreased the level of plasma MDA, while there was no effect on the anti-oxidation index.