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Objective:To investigate the effects of β-glucan on the activation and functions of mouse bone marrow-derived dendritic cells (BMDCs) induced under different conditions.Methods:Mouse bone marrow from the tibia and fibula was in vitro induced into FL-DCs and GM-DCs by FMS-like tyrosine kinase 3 ligand (Flt-3L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with IL-4 into, respectively. These cells were stimulated with whole glucan particles (WGP) and flow cytometry was performed to detect the expression of surface molecules such as CD40, CD80, MHCⅠ, MHCⅡ, CD8α, and CD11b on them. ELISA was used to detect the levels of IL-12p40, TNF-α, IL-6, and IL-10 in cell culture supernatants. The expression of each cytokine and chemokine receptor at the mRNA level was detected by real-time fluorescence quantitative PCR. CD8 + and CD4 + T cells in OT-Ⅰ and OT-Ⅱ mice were sorted out by magnetic bead sorting kit and co-cultured with FL-DCs and GM-DCs in the presence of ovalbumin (OVA). And then, the proliferation and differentiation of T cells were detected by flow cytometry. Results:WGP significantly promoted the expression of CD40, CD80, MHCⅠ, MHCⅡ and CD8α on FL-DCs and GM-DCs ( P<0.05). The secretion of IL-12p40 and TNF-α by FL-DCs and GM-DCs was significantly enhanced after WGP treatment ( P<0.05), while there are significant differences in the secretion of IL-6 and IL-10 between FL-DCs and GM-DCs. Real-time fluorescence quantitative PCR showed that WGP promoted the expression of chemokine receptors CXCR5 and CCR7 by GM-DCs ( P<0.001 and P<0.01), and the expression of CCR7 by FL-DCs ( P<0.0001). WGP promoted CD4 + T cells to secrete more IFN-γ and IL-17α when they were co-cultured with FL-DCs or GM-DCs ( P<0.05). Conclusions:WGP induces the maturation of BMDCs and improves the ability of BMDCs to activate effector T cells. Besides, WGP prompts the differentiation of BMDCs that are induced under different conditions to different Th cells.
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Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.
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Male , Female , Humans , Retrospective Studies , Atrial Fibrillation , Treatment Outcome , Cardiomyopathy, Hypertrophic/surgery , Mitral Valve Insufficiency/surgery , Ventricular SeptumABSTRACT
Objective:To investigate the effects of orlistat on the viability of human gall-bladder cancer (GBC) cells.Methods:The experimental study was conducted. The human GBC NOZ cells with high expression of FSAN was screened out through in vitro cultivating human GBC-SD, SGC-996 and NOZ cells. The cell proliferation assay, clone formation assay and protein detection experiment were used to analysis of the effects of orlistat on the viability of human GBC cells. Cell grouping: NOZ cells cultured with medium were set as the control group, cultured with medium + 10 μmol/L orlistat were set as the low-dose orlistat group, cultured with medium + 100 μmol/L orlistat were set as the high-dose orlistat group, respectively. Observation indicators: (1) expression of FASN protein in human GBC cells; (2) effects of orlistat on the proliferation of human GBC NOZ cells; (3) effects of orlistat on apoptosis of human GBC NOZ cells. Measurement data with normal distribution were represented as Mean± SD, the ANOVA test was used for comparison between groups and the least significant difference method was used for pairwise comparison. Results:(1) Expression of FASN protein in human GBC cells. Results of western blot showed that the relative expression of FASN protein in human GBC NOZ, GBC-SD and SGC-996 cells was 0.57±0.06, 0.12±0.04 and 0.10±0.02, respectively, showing a significant difference among them ( F=115.67, P<0.05). There were significant differences between the NOZ cells and the GBC-SD or the SGC-996 cells ( P<0.05), and there was no significant difference between the GBC-SD cells and the SGC-996 cells ( P>0.05). (2) Effects of orlistat on the proliferation of human GBC NOZ cells. ① Results of cell proliferation assay showed that the absorbance value of NOZ cells was 2.34±0.12, 1.57±0.08 and 1.07±0.13 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=205.88, P<0.05). ② Results of clone formation assay showed that the number of NOZ cells clones was 257±23, 153±11 and 83±11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=92.64, P<0.05). ③Results of western blot showed that the relative expression of Cyclin-D1 protein of NOZ cells was 2.31±0.10, 1.52±0.05 and 1.23±0.11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=120.73, P<0.05). The relative expression of CDK-4 protein of NOZ cells was 1.58±0.04, 1.21±0.02 and 1.19±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=110.45, P<0.05). (3) Effects of orlistat on apoptosis of human GBC NOZ cells. Results of western blot showed that the relative expression of Bcl-2 protein of NOZ cells was 1.07±0.03, 0.36±0.03 and 0.15±0.02 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=1 242.93, P<0.05). The relative expression of Bax protein of NOZ cells was 0.51±0.03, 0.38±0.05 and 1.38±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=583.51, P<0.05). Conclusion:Orlistat can inhibit the growth of human GBC NOZ cells and promote their apoptosis.
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Objective:To systematically evaluate the intervention effect of exposure and response prevention (ERP) on obsessive compulsive disorder (OCD).Methods:PubMed, Web of Science Core Collection, EBSCO, Cochrane Library, Embase, Science Direct, Wanfang Data, China National Knowledge Infrastructure and VIP-CSTJ were used to collect randomized controlled studies related to ERP for OCD.Randomized controlled studies that met the criteria were included, with the score of Yale-Brown obsessive-compulsive scale as the primary outcome indicator and the scores of anxiety and depression scale as secondary outcome indicators, while the included literatures were evaluated for literature quality and data extraction.Review Manager 5.3 and Stata 16.0 softwares were used to conduct Meta-analysis on the extracted data.Results:Twenty-seven studies with a total of 1 239 patients were included, and 599 cases in the ERP group and 640 cases in the control group.Meta-analysis results showed that the efficacy of ERP group was significantly better than that of blank control group(MD=-6.55, 95% CI: -8.75--4.35, P<0.001) and significantly better than chlorpromazine control group treatment (MD=-5.88, 95% CI: -8.20--3.56, P<0.001) for improving patients' obsessive-compulsive symptoms, but not significantly different from CBT intervention (MD=0.21, 95% CI: -1.62-2.04, P=0.82), and the efficacy of ERP and CBT had no significant during the post-intervention follow-up period (MD=0.41, 95% CI: -2.45-3.27, P=0.78). For improving patients' depressed mood, ERP was effective in improving patients' depressed mood (SMD=-0.45, 95% CI: -0.74--0.17, P=0.002), but not significantly different from CBT (SMD=-0.05, 95% CI: -0.27-0.16, P=0.62). For improving anxiety, the efficacy of ERP group was not different from that of control group (SMD=-0.17, 95% CI: -0.56-0.23, P=0.41). Conclusion:ERP has good feasibility in improving obsessive-compulsive symptoms and depression in patients with OCD.However, long-term efficacy was not verified for improving anxiety and maintaining long-term efficacy during the follow-up period.
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Objective:To investigate the effect of tripartite motif-containing 23 (Trim23) on the differentiation and maturation of dendritic cells and the possible mechanism.Methods:Mouse bone marrow-derived dendritic cells (BMDCs) were prepared from bone marrow cells of C57BL/6 mice with the presence of Flt3L. Real-time quantitative PCR and Western blot were used to detect the expression of Trim23 in BMDCs after LPS stimulation. An overexpression vector for full-length Trim23 (Trim23 OE) was constructed and transfected into BMDCs, and the pcDNA3.1 empty vector was used as control. Flow cytometry was used to detect the expression of CD80, CD86, CD40 and MHCⅡ on the surface of vector-transfected BMDCs after LPS stimulation and ELISA was used to detect the secretion of IL-12p40, TNF-α, IL-6 and IL-10 by these cells. CD8 + and CD4 + T cells were isolated from spleen and lymph nodes of OT-Ⅰ and OT-Ⅱ mice by magnetic beads and co-cultured with LPS-treated BMDCs in the presence of ovalbumin (OVA). Flow cytometry was used to detect the proliferation and differentiation of CD8 + and CD4 + T cells. Western blot was performed to analyze the phosphorylation of p38, ERK1/2 and AKT in BMDCs. Two overexpression vectors for Trim23 mutants lacking RING or ARF domain (Trim23 ΔRING and Trim23 ΔARF) were constructed and transfected into BMDCs. Then flow cytometry and ELISA were used to detect the expression of surface molecules and cytokines. Results:The expression of Trim23 in BMDCs was significantly down-regulated after LPS stimulation. The expression of MHCⅡ, CD86 and CD80 and the secretion of TNF-α and IL-6 decreased significantly in BMDCs overexpressing Trim23. Furthermore, overexpression of Trim23 inhibited the ability of BMDCs to induce the proliferation and differentiation of CD4 + T cells and the proliferation of CD8 + T cells. Western blot showed that the phosphorylation of p38 and ERK1/2 decreased significantly in Trim23-overexpressing BMDCs. Compared with wildtype Trim23, overexpression of Trim23 ΔRING had no significant influence on the expression of surface molecules (MHCⅡ and CD86) and the secretion of cytokines (TNF-α and IL-6) in BMDCs stimulated by LPS. Conclusions:Trim23 overexpression inhibited the maturation and immune activation of BMDCs via MAPK signal pathway and its RING domain. This study provided reference for targeting Trim23 to improve the immune response of dendritic cell-based tumor vaccines.
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Objective To explore the effects of transurethral en-blocresection of bladder tumor(TeURBT)on urination function,serum chitinase protein 40(YKL-40),bladder specific nuclear matrix protein-1(BLCA-1),and p-oxyfossase-1(PON-1)levels in patients with non-muscle invasive bladder cancer(NMIBC).Methods 74 patients with NMIBC admitted to our Hospital from January 2019 to May 2022 were divided into TeURBT group and transurethral resection of bladder tumor(TURBT)group by random lottery,with 37 cases in each group.The effective tumor clearance rate,surgery and urination function indexes were compared between the two groups.Blood samples were collected before surgery,3 months,6 months and 12 months after surgery to determine the levels of serum YKL-40,BLCA-1 and PON-1,and the recurrence rate was analyzed at 12 months of follow-up.Results The effective resection rate of bladder tumor was 100.00%in both groups.The operative time in TeURBT group was significantly longer than that in TURBT group(P<0.05),and the intraoperative blood loss,catheter indwelling/bladder irrigation/hospitalization time in TeURBT group were significantly less than those in TURBT group(P<0.05).Urinary output and maximum urinary flow per second in both groups significantly increased on postoperative day 14(P<0.05),but there was no statistically significant difference in the above indexes between the two groups on postoperative day 14(P>0.05).The levels of serum YKL-40 and BLCA-1 in the two groups at 3,6 and 12 months after surgery significantly decreased(P<0.05),while the level of PON-1 significantly increased(P<0.05).There were no statistically significant differences in serum YKL-40 and PON-1 levels between the two groups at 3 and 6 months after surgery(P>0.05),while serum YKL-40 and BLCA-1 levels in the TeURBT group were significantly lower than those in the TURBT group at 12 months after surgery(P<0.05),and PON-1 levels were significantly higher than those in the TURBT group(P<0.05).The stages in the TeURBT group could be accurately diagnosed after operation,and the postoperative pathological stages were Ta stage in 24 cases and T1 stage in 13 cases.The total incidence of postoperative complications in TeURBT group and cumulative incidence of recurrence in 1-year follow-up were 5.40%,which was significantly lower than 24.32%and 21.62%in TURBT group(P<0.05).Conclusion The effective resection rate of TeURBT and TURBT in the treatment of NMIBC tumor is similar,which can effectively improve the urination function of patients,downregulation of serum YKL-40 and BLCA-1 levels,and up-regulation of PON-1 levels.Compared with TURBT,TeURBT has advantages of less intraoperative blood loss,fewer postoperative complications,faster recovery,and lower recurrence rate.
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Objective:To analyze the clinical value of noninvasive pressure strain loop (PSL) in assessing left ventricular myocardial work in patients with essential hypertension.Methods:In this cross-sectional study, 66 patients with essential hypertension who were admitted to the Affiliated Hospital of Yangzhou University from August to December 2020 were continuously enrolled. According to left ventricular mass index (LVMI) >95 g/m 2 in women and >115 g/m 2 in men,≤95 g/m 2 in women and ≤115 g/m 2 in men, the 66 patients were divided into left ventricular hypertrophy (LVH) group (14 cases) and non-left ventricular hypertrophy (NLVH) group (52 cases). Furthermore, the NLVH group was divided into a mild group (30 cases) and a moderate/severe group (22 cases) according to the systolic blood pressure of 140~159 mmHg (1 mmHg=0.133 kPa) and ≥160 mmHg. Another 25 healthy adults who underwent physical examination during the same period were included as healthy control group. The height, weight and blood pressure were measured in all the subjects, and routine echocardiography and speckle tracking imaging analysis were performed. PSL results were obtained by combining the results of speckle tracking imaging analysis with systolic blood pressure. The differences of general clinical data, basic parameters of two-dimensional ultrasound and myocardial work parameters of PSL (global work index, global effective work, global wasted work, and global work efficiency) were compared among the groups, and the clinical value of PSL in assessing left ventricular myocardial work in patients with essential hypertension was analyzed. Results:There was no significant difference in left ventricular ejection fraction among all groups (all P>0.05). The global work index of moderate/severe NLVH group was significantly higher than that of mild NLVH group, LVH group and healthy control group [(2 630±231) vs (2 254±179), (1 847±261), (1 724±209) mmHg%]. The global effective work of moderate/severe NLVH group was significantly higher than that of LVH group and healthy control group [(2 965±261) vs (2 330±258) and (2 121±163) mmHg%] (all P<0.05). The global wasted work of LVH group was significantly higher than that of moderate/severe NLVH group, mild NLVH group and healthy control group [(248±107) vs (141±57), (116±57), (83±58) mmHg%] (all P<0.05). The global work efficiency was significantly lower than that of moderate/severe NLVH group, mild NLVH group and healthy control group (89.1%±3.9% vs 94.3%±1.9%, 95.0%±1.8%, 95.8%±2.3%) (all P<0.05). With the increase of blood pressure, the PSL decreased in the LVH group and increased in the other three groups. The bull′s eye diagram of myocardial work in the healthy control group was uniform green (normal effective work area), red began to appear in the mild NLVH group (high intensity myocardial work area), red area increased in the moderate/severe NLVH group, and blue appeared in the LVH group (ineffective work area). Conclusions:PSL has good clinical value in assessing left ventricular myocardial work in patients with primary hypertension. The parameters derived from PSL data can sensitively identify impaired systolic function in individuals with normal left ventricular ejection fraction.
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The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC50 = 16.94 μg·mL-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.
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OBJECTIVES@#To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response.@*METHODS@#A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA).@*RESULTS@#For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg.@*CONCLUSIONS@#There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.
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Humans , Infant, Newborn , Arginine/analogs & derivatives , Biomarkers , Hypertension, Pulmonary/drug therapy , Prospective StudiesABSTRACT
Objective To investigate the prevalence of Schistosoma japonicum infection in wild mice in Shitai County, Anhui Province, so as to provide insights into precise control of the source of S. japonicum infections. Methods Wild mice were captured using the trapping method for three successive nights at snail-infested settings from Jitan Village of Jitan Township, and Shiquan Village and Xibai Village of Dingxiang Township, Shitai County, Anhui Province in June and October, 2018. All trapped wild mice were sacrificed and liver and mesenteric vein specimens were collected for detection of S. japonicum eggs using microscopy, while the fecal samples in mouse intestines were collected for identification of S. japonicum infections using Kato-Katz technique. In addition, the population density of trapped wild mice was estimated and the prevalence of S. japonicum infection was calculated in trapped wild mice. Results A total of 376 wild mice were trapped from three villages in Shitai County. The population density of trapped wild mice was 9.1% (376/4 124), and the prevalence of S. japonicum infection was 24.2% (91/376) in trapped wild mice. The highest prevalence of S. japonicum infection was detected in Shiquan Village of Dingxiang Township (30.1%), and the lowest prevalence was seen in Xibai Village of Dingxiang Township; however, there was no significant difference in the prevalence of S. japonicum infection in trapped wild mice among three villages (χ2= 4.111, P > 0.05). In addition, there was no significant difference in the prevalence of S. japonicum infection in wild mice captured between on June (26.8%, 34/127) and October (22.9%, 57/249) (χ2 = 0.690, P = 0.406). The trapped wild mice included 6 species, including Rattus norvegicus, Niviventer niviventer, R. losea, Apodemus agrarius, Mus musculus and N. coning, and the two highest prevalence of S. japonicum infection was detected in R. losea (34.9%, 22/63) and R. norvegicus (31.2%, 44/141). Conclusions The prevalence of S. japonicum infections is high in wild mice in Shitai County, and there is a natural focus of schistosomiasis transmission in Shitai County.
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Circadian rhythm is mainly regulated by circadian clock genes, which is the result of biological evolution and plays an important role in maintaining the normal structure and function of organisms. When the circadian rhythm is disturbed or out of balance, it will have adverse health consequences. In addition to studies on diseases of nervous system, endocrine system or cardiovascular system, it has been found that circadian rhythm disorder mediated by circadian clock gene also plays a key regulatory role in the occurrence and development of hepatocellular carcinoma, which is a potential diagnostic marker and therapeutic target. In this paper, the research on the role of circadian clock gene in hepatocellular carcinoma in recent years is reviewed, and the research progresis and existing problems of targeting circadian clock gene in the treatment of hepatocellular carcinoma are discussed.
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Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.
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BACKGROUND@#Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD.@*METHODS@#This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0-52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study.@*DISCUSSION@#The tACS applied in this trial may have treatment effects on MDD with minimal side effects.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.
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Objective:To investigate the effects of β-glucan combined with agonistic anti-CD40 monoclonal antibody (5C11) on the immune functions of dendritic cells (DCs) and the possible molecular mechanism.Methods:Mononuclear cells were separated from fresh concentrated white cells (granulocytes) of healthy subjects using Ficoll density gradient centrifugation, and induced by GM-CSF and IL-4 to differentiate into immature DCs. Following various stimulation (5C11 alone, β-glucan alone, 5C11 combined with β-glucan), flow cytometry was used to detect the expression of CD40, CD80, CD83, CD86 and MHC-Ⅱ molecule HLA-DR on the surface of DCs. ELISA was used to detect the secretion of cytokines including IL-12, IL-6, TNF-α and IL-10. Western blot was used to detect the phosphorylation of proteins related to MAPK signaling pathway.Results:Flow cytometry suggested that β-glucan significantly induced the expression of co-stimulatory molecule CD40 on the surface of DCs ( P<0.05). After the DCs were co-stimulated with β-glucan and 5C11, CD80, CD83 and CD86 expression were further significantly increased, and a strong synergistic effect on CD83 expression, a key marker of DC maturation, was observed ( P<0.01). ELISA showed that β-glucan combined with 5C11 could significantly promote the secretion of cytokines such as IL-12, IL-6 and TNF-α by DCs, and have a synergistic effect on the secretion of IL-12, a critical cytokine in regulating DC functions ( P<0.01). Western blot indicated that the phosphorylation of p38 MAPK and p44/42 MAPK in DCs was increased significantly after combined treatment, and the phosphorylation started earlier and lasted longer compared to that in DCs stimulated with 5C11 or β-glucan alone ( P<0.01). Conclusions:This study suggested that β-glucan combined with 5C11 had a synergistic effect on promoting the maturation and improving the immune functions of DCs, providing a new strategy for the preparation of anti-tumor DC vaccines.
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Objective To analyze the endemic situation of schistosomiasis in national surveillance sites of Anhui Province from 2015 to 2018, so as to provide scientific evidence for schistosomiasis control and prevention in Anhui Province. Methods According to the National Schistosomiasis Surveillance Programme (2014 version), a total of 51 national schistosomiasis surveillance sites were assigned in Anhui Province in 2015, and Schistosoma japonicum infections in humans and livestock and snail distribution were monitored from 2015 to 2018. Results A total of 89 638 local residents and 42 609 mobile populations received serological screening of schistosomiasis in 51 national surveillance sites of Anhui Province from 2015 to 2018, and the sero-prevalence of S. japonicum infections was 1.41% to 3.69% in local residents and 0.84% to 2.13% in mobile populations, respectively. There were 5 egg-positive local residents and 1 egg-positive mobile populations detected in 2015, with occupations of farmers and fishermen. There were 6 405 livestock detected for S. japonicum infections, and no egg-positives were identified. Among an area of 12 661 hm2 surveyed in the national schistosomiasis surveillance sites of Anhui Province from 2015 to 2018, the areas of snail habitats were 2 461.27 to 2 628.96 hm2, andthemeandensityoflivingsnailswas 0.3757 to 0.4330 snails/0.1 m2, with no S. japonicum infections identified in snails. Conclusions The endemic situation of schistosomiasis is at a low level in Anhui Province; however, the risk of schistosomiasis transmission remains in local regions of the province. The construction of the surveillance-responsesystemshouldbereinforcedtoconsolidatetheachievementsofschistosomiasis control in Anhui Province.
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Aloin is a small-molecule drug well known for its protective actions in various models of damage. Traumatic brain injury (TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier (BBB) often leads to an adverse prognosis. Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear, we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models. Adult male C57BL/6 mice underwent controlled cortical impact injury, and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury, then both received aloin treatment. In the animal experiments, we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema, decrease disruption of the BBB, and improve neurobehavioral performance after cortical impact injury. In the cellular studies, the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury. The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase, the activation of p65 nuclear factor-kappa B, and the ratios of B cell lymphoma (Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3. We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells. Aloin may thus be a promising therapeutic drug for TBI.
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Objective@#To explore the clinical application value of enhanced recovery after surgery (ERAS) in the laparoscopic surgery for cholecystolithiasis comorbid with choledocholithiasis.@*Methods@#The prospective study was conducted. The clinicopathological data of 52 patients with cholecystolithiasis comorbid with choledocholithiasis who were admitted to the Third Affiliated Hospital of Zunyi Medical University from September 2016 to September 2018 were collected. Patients were divided into 2 groups by random number table: patients in observation group received laparoscopic cholecystectomy + choledocholithotomy + choledochoscopic exploration + T-tube drainage (or primary suture of common bile duct) and perioperative management guided by the concept of enhanced recovery after surgery (ERAS), and patients in control group received traditional perioperative management. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) postoperative complications; (4) postoperative pain scores; (5) changes in hepatic function and blood routine during perioperative period. Follow-up using outpatient examination and telephone interview was performed to detect complications during the postoperative 6 months up to March 2019. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the paired t test or repeated ANOVA. Count data were described as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability.@*Results@#Fifty-two patients were screened for eligibility, including 20 males and 32 females, aged 25-68 years, with an average age of 53 years. There were 30 patients in the observation group and 22 in the control group. (1) Surgical situations: the operation time and volume of intraoperative blood loss were (133±19)minutes and (47±21)mL in the observation group, and (136±22)minutes and (49±23)mL in the control group, respectively, showing no significant difference between the two groups (t=-0.386, -0.211, P>0.05). (2) Postoperative situations: time to out-of-bed activity, time to initial food intake, time to first anal flatus, duration of postoperative hospital stay, and hospital expenses were (18±4)hours, (19±5)hours, (28±2)hours, (4.0±1.0)days, and (1.82±0.22)×104 yuan in the observation group, and (29±7)hours, (46±9)hours, (37±4)hours, (6.6±1.6)days, and (2.25±0.29)×104 yuan in the control group, respectively, showing significant differences between the two groups (t=-7.054, -14.169, -9.426, -6.582, -5.809, P<0.05). (3) Postoperative complications: 1 of 30 patients in the observation group had postoperative biliary leakage, with a postoperative complication rate of 3.3%, and was cured after symptomatic support treatment. Six of 22 patients in the control group had postoperative complication, with a postoperative complication rate of 27.3%, including 2 of biliary leakage, 1 of hemorrhage, 1 of abdominal infection, 1 of pulmonary infection, 1 of urinary infection, and they were cured after symptomatic support treatment. There was a significant difference between the two groups (χ2=4.358, P<0.05). (4) Postoperative pain scores: from postoperative 6 hours to 48 hours, the postoperative pain score changed from 2.4±0.7 to 1.9±0.9 in the observation group, and from 4.1±0.7 to 2.9±0.9 in the control group, respectively, showing a significant difference in the changing trend between the two groups (F=78.053, P<0.05). (5) Changes in hepatic function and blood routine during perioperative period: from preoperation to postoperative 3 days, levels of alamine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBil), and count of white blood cells in the observation group changed from (77±20)U/L to (53±12)U/L, from (85±22)U/L to (61±17)U/L, from (166±39)U/L to (55±24)U/L, from (40±13)μmol/L to (29±12)μmol/L, from (7.0±2.0)×109/L to (6.8±1.9)×109/L, and changed from (79±23)U/L to (62±14)U/L, from (88±24)U/L to (64±17)U/L, from (179±34)U/L to (74±29)U/L, from (45±13)μmol/L to (35±12)μmol/L, from (7.9±2.4)×109/L to (7.5±1.9)×109/L in the control group, respectively. The levels of ALT, AST, GGT, TBiL, and count of WBC showed increasing at postoperative 1 day, and decreasing at postoperative 3 days. There was no significant difference in the changing trend between the two groups (F=0.058, 0.471, 3.021, 1.593, 2.172, P>0.05).@*Conclusion@#ERAS is safe and effective in the laparoscopic surgery for choledocholithiasis comorbid with cholecystolithiasis.
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Objective To explore the clinical application value of enhanced recovery after surgery (ERAS) in the laparoscopic surgery for cholecystolithiasis comorbid with choledocholithiasis.Methods The prospective study was conducted.The clinicopathological data of 52 patients with cholecystolithiasis comorbid with choledocholithiasis who were admitted to the Third Affiliated Hospital of Zunyi Medical University from September 2016 to September 2018 were collected.Patients were divided into 2 groups by random number table:patients in observation group received laparoscopic cholecystectomy + choledocholithotomy + choledochoscopic exploration +T-tube drainage (or primary suture of common bile duct) and perioperative management guided by the concept of enhanced recovery after surgery (ERAS),and patients in control group received traditional perioperative management.Observation indicators:(1) surgical situations;(2) postoperative situations;(3) postoperative complications;(4) postoperative pain scores;(5) changes in hepatic function and blood routine during perioperative period.Follow-up using outpatient examination and telephone interview was performed to detect complications during the postoperative 6 months up to March 2019.Measurement data with normal distribution were represented as Mean ± SD,and comparison between groups was analyzed using the paired t test or repeated ANOVA.Count data were described as absolute numbers and percentages,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Results Fifty-two patients were screened for eligibility,including 20 males and 32 females,aged 25-68 years,with an average age of 53 years.There were 30 patients in the observation group and 22 in the control group.(1) Surgical situations:the operation time and volume of intraoperative blood loss were (133± 19) minutes and (47 ± 21) mL in the observation group,and (136±22) minutes and (49±23)mL in the control group,respectively,showing no significant difference between the two groups (t=-0.386,-0.211,P>0.05).(2) Postoperative situations:time to out-of-bed activity,time to initial food intake,time to first anal flatus,duration of postoperative hospital stay,and hospital expenses were (18±4) hours,(19±5) hours,(28±2)hours,(4.0± 1.0)days,and (1.82±0.22) × 104 yuan in the observation group,and (29±7)hours,(46±9)hours,(37±4)hours,(6.6±1.6)days,and (2.25±0.29) ×104 yuan in the control group,respectively,showing significant differences between the two groups (t =-7.054,-14.169,-9.426,-6.582,-5.809,P<0.05).(3) Postoperative complications:1 of 30 patients in the observation group had postoperative biliary leakage,with a postoperative complication rate of 3.3%,and was cured after symptomatic support treatment.Six of 22 patients in the control group had postoperative complication,with a postoperative complication rate of 27.3%,including 2 of biliary leakage,1 of hemorrhage,1 of abdominal infection,1 of pulmonary infection,1 of urinary infection,and they were cured after symptomatic support treatment.There was a significant difference between the two groups (x2 =4.358,P < 0.05).(4) Postoperative pain scores:from postoperative 6 hours to 48 hours,the postoperative pain score changed from 2.4 ± 0.7 to 1.9± 0.9 in the observation group,and from 4.1 ± 0.7 to 2.9 ± 0.9 in the control group,respectively,showing a significant difference in the changing trend between the two groups (F=78.053,P<0.05).(5) Changes in hepatic function and blood routine during perioperative period:from preoperation to postoperative 3 days,levels of alamine aminotransferase (ALT),aspartate transaminase (AST),gamma-glutamyltransferase (GGT),total bilirubin (TBil),and count of white blood cells in the observation group changed from (77±20)U/L to (53± 12)U/L,from (85±22)U/L to (61± 17) U/L,from (166±39) U/L to (55±24) U/L,from (40± 13) μmol/L to (29±12) μmol/L,from (7.0±2.0) × 109/L to (6.8± 1.9) × 109/L,and changed from (79±23) U/L to (62± 14) U/L,from (88±24)U/L to (64± 17) U/L,from (179±34) U/L to (74±29) U/L,from (45± 13) μmol/L to (35±12) μmol/L,from (7.9±2.4)× 109/L to (7.5± 1.9)× 109/L in the control group,respectively.The levels of ALT,AST,GGT,TBiL,and count of WBC showed increasing at postoperative 1 day,and decreasing at postoperative 3 days.There was no significant difference in the changing trend between the two groups (F=0.058,0.471,3.021,1.593,2.172,P>0.05).Conclusion ERAS is safe and effective in the laparoscopic surgery for choledocholithiasis comorbid with cholecystolithiasis.
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Estimation of postmortem interval(PMI)plays a crucial role in forensic study and identifica-tion work. Because of the unique anatomy location, vitreous humor is considered to be used for estima-ting PMI, which has aroused interest among scholars, and some researches have been carried out. The detection techniques of vitreous humor are constantly developed and improved which have been gradually applied in forensic science, meanwhile, the study of PMI estimation using vitreous humor is updated rapidly. This paper reviews various techniques and instruments applied to vitreous humor detection, such as ion selective electrode, capillary ion analysis, spectroscopy, chromatography, nano-sensing technology, automatic biochemical analyser, flow cytometer, etc., as well as the related research progress on PMI es-timation in recent years. In order to provide a research direction for scholars and promote a more accu-rate and efficient application in PMI estimation by vitreous humor analysis, some inner problems are also analysed in this paper.
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Objective:To investigate the efficacy and the clinical value of magnetic resonance elastography(MRE) in diagnosis of hepatic fibrosis with Meta-analysis, and to provide basis for clinical treatment of hepatic fibrosis.Methods:The studies published before February 2, 2017 about MRE and staging of hepatic fibrosis in Chinese or English were retrived in the databases including PubMed, EMBase, Web of Science, Cochrane Library,CNKI, CBMDisc,VIP, Wanfang data, and supplemented by manual retrieval for relevant literatures.The inclusion and exclusion criterions were used to select and extract the literatures.The literatures qualitie were valuated based on QUADAS-2 tool.The sensitivity(SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (+LR), negative likelihood ratio (-LR) on the groups of F0 vs F1-F4,F0-F1 vs F2-F4,F0-F2 vs F3-F4, F0-F3 vs F4 and heterogeneity were combined and tested with Stata software respectively.HSROC and AUROC were also implemented.Results:A total of 1 332 studies were searched, and 22 were included.21 of them were in English and 1 in Chinese.The results of Meta analysis showed that the SENp, SPEp, +LRp,-LRp, DOR and AUROC in F0 vs F1-F4 group were 88.8%(85.0-91.7),95.9%(91.5-98.0),21.435(10.215-44.979),0.117(0.086-0.159),183.187(72.533-462.650) and 0.96(0.94-0.98) ,respectively;the SENp, SPEp, +LRp,-LRp, DOR and AUROC in F0-F1 vs F2-F4 group were 93.3%(89.2%-35.9%), 94.1%(90.2%-96.5%),15.839(9.344-26.848),0.072(0.044-0.117),221.224(100.980-484.648) and 0.98(0.96-0.99),respectively;the SENp, SPEp, +LRp, -LRp, DOR and AUROC in F0-F2 vs F3-F4 group were 92.9%(88.9%-95.5%),94.6%(91.2%-96.8%),17.348(10.496-28.671),0.075(0.048-0.119),230.434(111.482-476.317)0.98(0.96-0.99), respectively;the SENp, SPEp, +LRp,-LRp, DOR and AUROC in F0-F3 vs F4 group were 97.7%(93.0%-99.3%),93.2%(90.3%-95.2%),14.337(9.910-20.742),0.025(0.008-0.075),580.405(144.871-2325.307) and 0.98(0.96-0.99),respectively.Conclusion:MRE,as a new and noninvasive imaging method, has high diagnostic value in all stages of hepatic fibrosis, which can provide a reliable reference for clinical precise treatment of hepatic fibrosis.