ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg^-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg^-1） and model groups （50， 100， 150 mg·kg^-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the C_max and AUC in the tumor significantly increased， T_max shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg^-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.

OBJECTIVE: To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD). METHODS: Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation Surveyor^TM software. RESULTS: The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature. CONCLUSION This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".
Female ; Humans ; Afibrinogenemia/congenital* ; East Asian People ; Fibrinogen/genetics* ; Mothers ; Mutation ; Pedigree

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

Objective:To study the feasibility, safety and technique for laparoscopic anatomical liver resection of segment 8.Methods:The clinical data of 9 patients who underwent laparoscopic anatomical liver resection of segment 8 from January 2015 to December 2019 at Hunan Provincial People's Hospital were retrospectively analyzed. There were 6 males and 3 females, with age ranging from 29 to 67 years (average 53.6 years). The operation time, intraoperative blood loss , postoperative hospital stay, postoperative complications, and long-term survival and recurrence rates on follow-up were analysed.Results:Laparoscopic anatomical liver resection of segment 8 was successfully carried out in these patients. The mean operative time was 188.9 min(range 140-240 min). The mean estimated intraoperative blood loss was 117.8 ml (range 20-300 ml). The postoperative hospital stay was 6.9 days (range 3-12 days). One patient developed pleural effusion after operation and responded to conservative treatment. Another patients developed ascites with delayed extubation. The patient was successfully treated with conservative treatment. No patients developed complications above Clavien Dindo Ⅲa. There were no perioperative deaths. The postoperative pathological results showed hepatocellular adenoma ( n=2), hepatocellular carcinoma ( n=4), cholangiocarcinoma ( n=1), and metastatic liver cancer ( n=2). On follow-up for 12-58 months (median 22 months) one patient with hepatocellular carcinoma developed recurrence at 18 months after operation and was treated with microwave ablation. The other patients were well on follow-up. Conclusions:With adequate preoperative evaluation, reasonable case selection, rigorous surgical planning, and skilled laparoscopic techniques, laparoscopic anatomical liver resection of segment 8 was safe and feasible, and the short-term efficacy was good in this study.

Objective:To explore the effect of the interval of radical prostatectomy after prostate puncture on the perioperative period and prognosis of patients.Methods:Patient’s data from September 2016 to September 2018 whom performed laparoscopic radical prostatectomy at the Affiliated Hospital of Xuzhou Medical University were collected and retrospectively analyzed. All prostate biopsy confirmed prostate cancer and 66 patients underwent laparoscopic radical prostatectomy. The average age was (70.11 ± 5.01) years, ranged from 60 to 79 years. The patients were divided into two groups according to the interval time from prostate biopsy to laparoscopic radical prostatectomy: <7 d group ( n=32) and 6-8 weeks group ( n= 34). The operation time, intraoperative blood loss, postoperative hospital stays, positive rate of incisional margin, postoperative urinary incontinence rate and the rate of urinary incontinence 6 months after operation, rate of postoperative erectile dysfunction and bone metastasis were compared and analyzed between the two groups. When the data conformed to the normal distribution, the data were expressed in Mean±standard deviation ( Mean± SD), and the independent sample t-test was used to evaluate the statistical significance between groups. When the data did not conform to the normal distribution, the measurement data was expressed as Median (interquartile range) [ M( P25, P75)], and the Mann-Whitney U test was used for the comparison between groups. Count data comparison between groups using Chi-square test or Fisher exact probability method. Unconditional multivariate Logistic regression was used to analyze the relationship between outcome and exposure. Results:All the 66 patients successfully underwent surgery, the surgery success rate was 100%. The average operation time of <7 d group and group 6-8 weeks group was [185.00(174.50, 193.50)] min and [183.00(175.00, 187.50) min], respectively, the difference was not statistically significant ( P=0.685 8, U=512.0). The average intraoperative blood loss of group <7 d group and 6-8 weeks group was [185.50(177.75, 205.25)]ml, [189.00(180.75, 206.00)] ml, respectively, the difference was not statistically significant ( P=0.685 9, U=512.0). The average postoperative hospital stays of <7 d group and 6-8 weeks group was [14.00(11.75, 16.00)] d, [13.50(12.00, 15.00)] d, respectively, the difference was not statistically significant ( P=0.785 7, U=522.5). The positive rate of incisal margin of<7 d group and 6-8 weeks group was 18.75%, 14.71%, respectively, the difference was not statistically significant ( P=0.659 5, χ2=0.194). The postoperative urinary incontinence rate of <7 d group and 6-8 weeks group was 6.25% and 8.82%, respectively, the difference was not statistically significant ( P=1.000 0). The urinary control after follow-up for six months of <7 d group and 6-8 weeks group was 6.25% and 2.94%, respectively, the difference was not statistically significant ( P=0.607 7). The postoperative erectile dysfunction rate of<7 d group and group 6-8 weeks group was 9.38% and 8.82%, respectively, the difference was not statistically significant ( P=1.000 0). The postoperative bone metastasis rate of group<7 d and 6-8 weeks group was 6.25% and 5.88%, respectively, the difference was not statistically significant ( P=1.000 0). Conclusions:Performing laparoscopic radical prostatectomy within 7 days following prostate biopsy did not adversely affect the postoperative outcomes and prognosis, also not increased postoperative complications, can shorten the patient′s treatment cycle.

Follow-up is a crucial step for the screening of neonatal genetic and metabolic diseases, which can directly influence the detection, diagnosis, efficacy of treatment, as well as the quality of neonatal screening. In view of the lack of follow-up, full understanding, and inconsistent requirement between various agencies and personnel in China, there is an urgent need for standardization. The Committee for Proficiency Testing of the Neonatal Genetic Metabolic Disease Screening Center of the National Health Committee of China has organized the writing of expert consensus for follow-up of neonatal genetic and metabolic disease screening after thorough discussion, so as to guide the follow-up work and improve its quality.
China ; Consensus ; Follow-Up Studies ; Genetic Diseases, Inborn ; diagnosis ; Humans ; Infant, Newborn ; Metabolic Diseases ; diagnosis ; genetics ; Neonatal Screening

Objective:To observe the influence of Xuebijing injection on the inflammatory markers and prognosis of coronavirus disease 2019 (COVID-19) patients.Methods:Sixty severe COVID-19 patients admitted to Changsha Public Health Treatment Center (North Hospital of the First Hospital of Changsha City) from January to March in 2020 were randomly divided into routine treatment group, Xuebijing 50 mL group and Xuebijing 100 mL group, with 20 cases in each group. The routine treatment group was treated according to the National Health Commission's guide for COVID-19. On the basis of conventional treatment, Xuebijing injection was injected by 50 mL twice a day for 7 days in Xuebijing 50 mL group, while by 100 mL twice a day for 7 days in Xuebijing 100 mL group. The blood routine test, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, 2019 novel coronavirus (2019-nCoV) nucleic acid test and disease classification of three groups before and 8 days after treatment were observed.Results:① After treatment, the white blood cell count (WBC) and lymphocyte count (LYM) of three groups increased, meanwhile CRP and ESR decreased. Compared with routine treatment group, the WBC count of Xuebijing 100 mL group after treatment significantly increased (×10 9/L: 7.12±0.55 vs. 5.67±0.51, P < 0.05), and the levels of CRP and ESR in Xuebijing 50 mL and 100 mL groups significantly decreased [CRP (mg/L): 32.3±4.6, 28.0±6.2 vs. 37.3±5.9; ESR (mm/1 h): 45.9±5.7, 40.5±7.4 vs. 55.3±6.6, all P < 0.05]. Compared with Xuebijing 50 mL group, the increase of WBC, and the decrease of CRP and ESR were more significant in Xuebijing 100 mL group [WBC (×10 9/L): 7.12±0.55 vs. 5.82±0.49, CRP (mg/L): 28.0±6.2 vs. 32.3±4.6, ESR (mm/1 h): 40.5±7.4 vs. 45.9±5.7, all P < 0.05]. ② After treatment, the APACHEⅡscore of three groups decreased. In Xuebijing 100 mL group, the APACHEⅡscore after treatment was significantly lower than those in routine treatment and Xuebijing 50 mL groups (12.3±1.5 vs. 16.5±1.6, 15.9±1.4, both P < 0.05). After treatment, the 2019-nCoV nucleic acid test in three groups partly turned negative, with 9 cases in routine treatment group, 8 cases in Xuebijing 50 mL group and 9 cases in Xuebijing 100 mL group, without significant difference ( P > 0.05). The conditions of patients in the three groups were improved after treatment, among them, 8 cases in the routine treatment group were transformed into common type, 1 case into critical type; 9 cases and 12 cases of Xuebijing 50 mL group and 100 mL group were transformed into common type respectively. Xuebijing 100 mL group was improved more obviously than Xuebijing 50 mL group and routine treatment group (both P < 0.05). Conclusion:The Xuebijing injection can effectively improve the inflammatory markers and prognosis of severe COVID-19 patients.

This paper summarizes the factors affecting schistosomiasis transmission in the middle and lower reaches of the Yangtze River before and after the completion of the Three Gorges Dam and analyzes schistosomiasis prevalence trends to provide a basis for the application of the Three Gorges project methodologies in other areas.The Three Gorges Dam has demonstrated a positive effect on schistosomiasis control.Hubei,Hunan,Jiangxi,Anhui,and Jiangsu in the middle and lower reaches of the Yangtze River are currently regions with a high prevalence of schistosomiasis.These five provinces contained 97.62％ of known snail areas and 93.66％ of calculated schistosomiasis cases with 90.07％ of counties (cities,districts) not yet meeting the criteria for schistosomiasis transmission interruption by the end of 2016.After the Three Gorges Dam was built,the prevalence of schistosomiasis in the middle and lower reaches of the Yangtze River decreased.By the end of 2016,the estimated number of cases decreased by 92.75％ and the snail habitat areas decreased by 6.56％ compared to 2004.No acute schistosomiasis cases have occurred for two consecutive years since 2015.

Objective To explore the effect and potential mechanism of suppressors of cytokine signaling 3 (SOCS3) knockout on cell viability and apoptosis of retinal ganglion cells (RGCs) after optic nerve injury.Methods The optic nerve transection was used to construct optic nerve injury model of rats,and RGCs were isolated after optic nerve injury.The experimental animals were divided into optic nerve transection injury (ONT) group and sham-operation (Sham) group.The expression of SOCS3 in RGCs was detected by Western blot and RT-PCR in each group.Subsequently,SOCS3 siRNA was transfected into RGCs of Sham group and ONT group,and the experimental were further subdivided into blank control group,negative control group and SOCS3 silence groups.Cell viability was measured by CCK8 and MTr methods.Apoptosis was detected by Hoechst 33342 staining and flow cytometry.Furthermore,the mTOR siRNA and SOCS3 siRNA were co-transfected into RGCs,and cell viability and apoptosis were detected.Results The expression of SOCS3 was dramatically increased at 3 days after injury in the ONT group when compared with Sham group (P =0.049),and it showed an increased tendency gradually along with the extension of injury time.Compared with the blank control in the ONT group,SOCS3 silence markedly promoted cell viability [(49.47 ± 7.35) ％ vs.(73.24 ± 8.70) ％],reduced cell growth inhibition [(27.25 ±0.75)％ vs.(10.96 ± 1.07)％] and apoptosis [(23.06 ± 1.43)％ vs.(10.65 ± 1.77)％].The result of Hoechst 33342 staining indicated that SOCS3 silence ameliorated the cell apoptosis induced by ONT.In addition,SOCS3 silence significantly improved pS6 expression at 2 weeks after injury,and mTOR and SOCS3 co-silence reduced cell viability,increased cell growth inhibition and apoptosis compared with SOCS3 silence group after injury.Conclusion SOCS3 silence promotes injury-induced cell viability of RGCs and suppresses injury-induced apoptosis of RGCs via up-regulating mTOR activity in the later period of injury.

Objective To investigate the expression of gastric and intestinal phenotypic markers in Siewert typeⅡand Ⅲ early gastroesophageal junction(GEJ) cancer, and to explore its correlation with clinic-pathological features.Methods From April 2010 to July 2015, 53 cases diagnosed as early GEJ cancer were enrolled.The gastric and intestinal phenotypic markers such as mucin5AC(MUC5AC),mucin6(MUC6),mucin2(MUC2),caudal related homeodomain transcription 2(CDX2) and cluster of differentiation 10(CD10) were detected, and then the patients were divided into gastric type, gastrointestinal type, intestinal type and non-classified type according to the results of immunohistochemical staining.Combined with Siewert classification the clinicopathological features were analyzed.Chi square test or Fisher′s exact test was performed for statistical analysis.Results In the cancer tissues of 47 patients with Siewert type Ⅱand Ⅲ early GEJ cancer, the case numbers of positive expression of MUC5AC,MUC6,MUC2, CDX2 and CD10 were 21(44.7%),19(40.4%),31(66.0%),27(57.4%) and 17(36.2%),respectively;the case numbers of gastric type, gastrointestinal type, intestinal type and non-classified type were 11(23.4%),14(29.8%),21(44.7%) and one(2.1%), respectively.The positive expression rates of MUC5AC and MUC6 in Siewert typeⅡwere 55.9%(19/34) and 50.0%(17/34),which were higher than those of Siewert typeⅢ(2/13), and the positive expression rate of MUC2 was 55.9%(19/34), which was lower than that of Siewert typeⅢ(12/13), and the differences were statistically significant (x2=6.240,4.679 and 4.053;all P<0.05).In Siewert typeⅡ, the proportion of intestinal type was 32.4%(11/34), which was lower than that of Siewert typeⅢ(10/13), and the differences were statistically significant (x2=7.142,P=0.010).In patients with Siewert typeⅡand Ⅲ early cancer, males predominated in intestinal type which were mostly well differentiated type with less submucosal carcinoma.The maximum diameter of tumor was less than those of gastric type and gastrointestinal type.In paracancerous mucosal tissues, the incidences of intestinal metaplasia in gastrointestinal type and intestinal type were 11/14 and 81.0%(17/21), which were higher than that of gastric type (3/11);the incidences of atrophy in gastrointestinal type and intestinal type were 12/14 and 85.7%(18/21),which were higher than that of gastric type (4/11),and the differences were statistically significant (Fisher′s exact test,all P<0.05).Conclusions Siewert typeⅡand Ⅲ early GEJ cancer can directly originated not only from gastric mucosa, but also from gastrointestinal and intestinal mucosa.Atrophy and intestinal metaplasia could exist before cancer genesis.