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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.
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Objective:To analyze clinical characteristics and genetic characteristics of children with ATP sensitive potassium passage (K ATP-HI). Methods:Forty-five children with genetically confirmed K ATP-HI and their families admitted to Beijing Children′s Hospital of Capital Medical University between February 2002 and December 2018 were selected as the study subjects. A detailed retrospective analysis of the patient's clinical characteristics, diagnosis and treatment process, disease-causing gene carrying status and later follow-up data was performed. ABCC8/KCNJ11 gene was sequenced by second-generation sequencing technology. Results:Among 45 children with K ATP-HI, 34 cases (75.6%) were neonatal onset, the first symptoms of 21 cases (46.7%) were convulsions. 39 cases had been treated with diazoxide, including 12 cases (30.8%) with good efficacy, 16 cases (41%) with poor efficacy and 11 cases with uncertain efficacy. Octreotide was further applied in 18 patients with uncertain or ineffective efficacy after diazoxide treatment, and 13 cases (72.2%) were effective, 3 cases were ineffective, and 2 cases were uncertain. 10 CHI patients who were ineffective to drug treatment or had clearly focal lesions confirmed by 18F-dopa positron emission by computed tomography ( 18F-DOPA PET) scans had undergone surgical treatment, 8 of which underwent partial pancreatectomy and blood glucose returned to normal after the operation; the other 2 cases underwent subtotal pancreatectomy and both had secondary diabetes after operation. Among 45 children with K ATP-HI, 1 case carried both ABCC8 and KCNJ11 mutations, 10 cases carried ABCC8 compound heterozygous mutations, and the remaining 34 cases carried ABCC8/KCNJ11 single genetic mutation. Among them, 21 cases had paternal inheritance, and 3 cases had maternal inheritance, 6 cases were identified with de novo mutations. Conclusions:Diazoxide treatment was ineffective for most K ATP-HI children, but octreotide had a higher effective rate. Partial pancreatectomy for focal type patients had a higher cure rate, and there was a risk of secondary diabetes after subproximal pancreatectomy, so it was very important to clarify the histological type of children before surgery. ABCC8 gene mutations and KCNJ11 gene mutations were the main pathogenic genes of K ATP-HI. Among patients carrying mutations in single ABCC8 or KCNJ11 gene mutation, K ATP-HI inherited by paternity were the majority. Some K ATP-HI children can relieve the hypoglycemia symptoms by themselves.
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Objective:To analyze the functional connectivity (FC) characteristics of sensory motor network (SMN) in patients with bipolar disorder type Ⅰ (BD-Ⅰ) by independent component analysis (ICA), and explore the correlation between abnormal SMN and clinical symptoms.Methods:Eighteen patients with BD-Ⅰ (BD-Ⅰ group) and 20 matched normal controls (HC group) were included.Both groups received resting state fMRI (rs-fMRI) scanning.Based on ICA-fMRI data, one-sample t-test and two-sample t-test were used to analyze the components of SMN and to explore abnormal brain regions between the two groups.Functional network analysis (FNC) was also used to explore the functional connectivity between SMN and other brain networks.Pearson correlation analysis were conducted by SPSS 17.0 to measure the potential associations between intra-and inter-network functional connectivity and age, education, score of Bech-Rafaelsen mania rating scale (BRMS), score of positive and negative syndrome scale (PANSS) and other indicators. Results:In BD-Ⅰ group, the functional connection in the right paracentral lobule (MIN: x=8, y=-32, z=68, t=4.86, P<0.001) and the right postcentral gyrus (MIN: x=41, y=-26, z=53, t=3.33, P<0.001) in SMN were higher than those in HC group.Compared with HC group, the connectivity value in patients with BD-Ⅰ increased between SMN-DAN (0.247±0.073, -0.078±0.080, t=-2.974, P<0.01, FDR adjusted), while the connectivity value decreased between SMN-DMN(-0.037±0.054, 0.272±0.067, t=3.520, P<0.01, FDR adjusted) and between SMN-rFPN(-0.034±0.055, 0.231±0.070, t=2.939, P<0.01, FDR adjusted). Conclusion:The sensorimotor network of patients with BD-Ⅰ has abnormal functional connections within and between networks, and FC values in some networks are positively correlated with manic symptoms, which may be part of the neural mechanisms of patients with BD-Ⅰ.
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Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.
Subject(s)
Animals , Female , Mice , Artesunate , Drugs, Chinese Herbal/therapeutic use , Liver Cirrhosis/drug therapy , Mice, Inbred C57BL , Mitochondria , SchistosomiasisABSTRACT
OBJECTIVE@#To explore the effects of isobavachalcone (IBC) on cell death of human breast cancer MCF-7 cells and explore the possible mechanism.@*METHODS@#MCF-7 cells were treated with different concentrations of IBC, and the changes in cell proliferation were assessed using MTT assay. Apoptosis of MCF-7 cells following treatment with 10, 20, and 40 μmol/L IBC was analyzed using flow cytometry with annexin V-FITC/PI double staining and fluorescence microscopy, and the expressions of apoptosis- and autophagy-related proteins (Bax, Bcl-2, Akt, p-Akt, p62, and LC3) were detected with Western blotting. Electron microscopy was used to observe the changes in submicrostructure of the cells following treatment with 40 μmol/L IBC. JC-1 assay kit, ATP assay kit, and reactive oxygen species (ROS) kit were used to determine the effect of IBC on mitochondrial function of the cells.@*RESULTS@#MTT assay showed that IBC significantly inhibited the proliferation of MCF-7 cells in a concentration- and time-dependent manner, with IC50 values of 38.46, 31.31, and 28.26 μmol/L at 24, 48, and 72 h, respectively. IBC also concentration-dependently induced apoptosis of MCF-7 cells. IBC-induced cell death was inhibited by z-VAD-fmk, a caspase inhibitor (P < 0.05), but not by the necroptosis inhibitor necrostatin-1 (Nec-1). Western blotting showed that IBC-induced MCF-7 cell apoptosis by increasing Bax expression and down-regulating the expressions of Bcl-2, Akt and p-Akt-473 (all P < 0.05). With the increase of IBC concentration, the expression of autophagy-related protein p62 and the LC3-II/I ratio increased progressively. Electron microscopy revealed the presence of autophagic bodies in IBC-treated MCF-7 cells. IBC treatment also resulted in decreased mitochondrial membrane potential and intracellular ATP level and increased ROS accumulation in MCF-7 cells (P < 0.05).@*CONCLUSION@#IBC is capable of inducing both apoptosis and autophagy in MCF-7 cells, suggesting the potential value of IBC as a lead compound in the development of anti-breast cancer agents.
Subject(s)
Humans , Adenosine Triphosphate , Cell Death , Chalcones , MCF-7 Cells , Neoplasms , Proto-Oncogene Proteins c-akt , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , bcl-2-Associated X ProteinABSTRACT
Objective: To evaluate the vascular toxicity of chemicals by a real-time observation approach using the transgenic zebrafish. Methods: The spatiotemporal vascular alterations of transgenic zebrafish after chemical exposure were assessed by laser confocal microscopy and high-content screening analysis, respectively. Results: The method using Laser Confocal Microscopy (LCM) is easier to operate and yields high-resolution images, while it is lower throughput and inefficient. In contrast, high-content analysis (HCA) analysis obtains high-quality data of vascular toxicity manifesting whole blood vasculature, whereas it requires delicate operation procedures and advanced experimental conditions. Conclusion: Two kinds of zebrafish imaging methods each have advantages and disadvantages. LCM is suitable for the evaluation of a small number of chemicals. HCA, a cutting-edge technology, has great potential for chemical safety assessment allowing high throughput vascular toxicity tests of a good number of chemicals at a time.
Subject(s)
Animals , Animals, Genetically Modified , Cardiovascular System , Toxicity Tests , ZebrafishABSTRACT
Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.
Subject(s)
Humans , Cartilage, Articular/pathology , Chondrocytes/metabolism , Down-Regulation , Epigenesis, Genetic , Jumonji Domain-Containing Histone Demethylases/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism , Osteoarthritis/pathology , RNA, Small Interfering/pharmacologyABSTRACT
Objective:To explore the effect of cognitive-motor dual task training on vascular mild cognitive impairment (VaMCI) in old patients. Methods:From March to September, 2019, 76 old patients with VaMCI in three general hospitals were divided into control group (n = 38) and intervention group (n = 38). All the patients accepted health education, while the intervention group accepted cognitive-motor dual task training in addition, for three months. They were assessed with Montreal Cognitive Assessment-Beijing Version (MoCA-BJ) and Trail Making Test (TMT-A) before and after intervention, and the one-year incidence of fall before and after intervention was investigated in the intervention group. Results:Two cases in the control group and three cases in the intervention group dropped down. The total score and dimension scores of MoCA-BJ were more significantly in the intervention group than in the control group after intervention (|Z| > 2.002, P < 0.05), except the dimension of naming, while the time for TMT-A was significantly less (Z = -5.949, P < 0.001). The one-year incidence of fall decreased significantly during the year after intervention (χ2 = 10.080, P < 0.01). Conclusion:Cognitive-motor dual task training can improve the cognitive function of older VaMCI patients, especially for attention and executive function, and reduce the risk of fall.
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To screen the available tomato pollution-safe cultivar varieties and reduce the potential food safety risks in Cd-polluted areas, the differences of Cd accumulation in different tomato (Solanum lycopersicum) varieties in southern China were studied by soil culture and hydroponic experiments. Firstly, the high and low accumulation varieties were selected from 25 tomato varieties under 2.94 mg/kg Cd stress by soil culture test, and then the responses of high and low accumulation tomato varieties to Cd stress were determined by hydroponic experiments. The results of soil culture test show that under 2.94 mg/kg Cd stress, there were significant differences in plant height, total biomass and yield among 25 tomato cultivars, and the Cd contents of fruits of all 25 tomato cultivars exceeded the highest limit value (0.05 mg/kg) of CAC (Codex alimentarius commission). Through cluster analysis, 7, 4 and 14 varieties accumulating relatively high, medium, and low concentrations of Cd in the fruits were screened, among which the highest, the lowest, and the average Cd contents in the fruits were 3.06 mg/kg DW, 1.47 mg/kg DW, and 2.21 mg/kg DW, respectively. The results of hydroponic experiment show that under the same concentration of Cd stress, Qiantangxuri F1, a high Cd accumulating variety, absorbed Cd faster, accumulated more Cd, used shorter oxidative stress response time and had stronger tolerance to Cd than Zhefen 3053, a low Cd accumulating variety. The typical high and low Cd accumulating varieties can provide a reference for agricultural production in heavy metal polluted areas and the development of molecular-assisted breeding methods of PSC. At present, cultivating low Cd accumulating PSC varieties and dynamic monitoring of Cd contents in tomato fruits are feasible methods in medium and light Cd-polluted areas.
Subject(s)
Antioxidants , Cadmium/toxicity , China , Solanum lycopersicum , Plant Breeding , Plant Roots/chemistry , Soil Pollutants/toxicityABSTRACT
Objective@#To explore the clinical study of different frequency repetitive transcranial magnetic stimulation in the treatment of senile schizophrenia.@*Methods@#The 70 elderly schizophrenics admitted to Kangning Hospital Affiliated to Wenzhou Medical University from February 2018 to August 2019 were randomly divided into observation group (35 cases) and control group (35 cases). High frequency repetitive transcranial magnetic stimulation was used in the observation group and low frequency repetitive transcranial magnetic stimulation was used in the control group. Both groups were treated for 4 weeks. The changes of clinical global impression (CGI), positive and negative syndrome scale (PANSS), cognitive function rating scale for schizophrenia (SCoRS), scale of social-skills for psychiatric inpatients(SSPI) and serum sex hormone levels before and after treatment were compared between the two groups.@*Results@#After treatment, the CGI and PANSS scores of the two groups were lower than those before treatment [observation group:(2.43 ± 0.37) scores vs. (5.61 ± 0.58) scores, (35.73 ± 6.57) scores vs. (79.95 ± 8.98) scores, t=27.346 and 23.512; control group: (3.37 ± 0.48) scores vs. (5.49 ± 0.62) scores, (40.91 ± 8.17) scores vs. (78.64 ± 9.63) scores, t=15.996 and 17.675, P<0.05]; after treatment, the CGI and PANSS scores of the observation group were lower than those of the control group (t=9.176, 2.923, P<0.05). After treatment, the SCoRS scores of the two groups was lower than those before treatment (observation group: t=12.822, control group: t=7.402, P<0.05); after treatment, the SCoRS score of the observation group was lower than that of the control group [(27.92 ± 5.41) scores vs. (34.25 ± 6.17) scores] (t=4.564, P<0.05). The SSPI scores of the two groups increased after treatment (observation group: t=9.252; control group: t=3.671, P<0.05); after treatment, the SSPI scores of the observation group were higher than those of the control group [(35.74 ± 3.27) scores vs. (30.85 ± 2.28) scores](t=7.257, P<0.05). After treatment, the serum testosterone and prolactin levels in the two groups were higher than those before treatment (observation group: t=13.853, 15.198; control group: t=10.075 and 9.225, P<0.05); after treatment, the serum testosterone and prolactin levels in the observation group were higher than those in the control group (t=5.693 and 7.202, P<0.05).@*Conclusions@#High frequency repetitive transcranial magnetic stimulation is superior to low frequency repetitive transcranial magnetic stimulation in the treatment of senile schizophrenia, and the improvement of sex hormone level is superior to low frequency repetitive transcranial magnetic stimulation, and the improvement of cognitive and social functions is superior to low frequency repetitive transcranial magnetic stimulation.
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Objective@#To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome, and to analyze the pathogenic genes carried by some patients.@*Methods@#The clinical data of 6 patients were summarized. The pathogenic genes of 4 families were analyzed. Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation. The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA) gene and to identify the pathogenic mutation sites by comparing with normal sequencing results.@*Results@#All the children had typical clinical manifestations of the disease which has been previously reported in the literature, such as severe growth retardation, special skin manifestations, and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c. 1824C>T(p.G608G). The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c. 1968+ 2T>C, among which the mutation of IVS8-4 C>A has not been reported.@*Conclusions@#In Chinese children, both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging. It is easy to make a diagnosis based on clinical manifestations. Finding of the pathogenic gene may further confirm the diagnosis.
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Objective:To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome, and to analyze the pathogenic genes carried by some patients.Methods:The clinical data of 6 patients were summarized. The pathogenic genes of 4 families were analyzed. Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation. The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA) gene and to identify the pathogenic mutation sites by comparing with normal sequencing results.Results:All the children had typical clinical manifestations of the disease which has been previously reported in the literature, such as severe growth retardation, special skin manifestations, and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c. 1824C>T(p.G608G). The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c. 1968+ 2T>C, among which the mutation of IVS8-4 C>A has not been reported.Conclusions:In Chinese children, both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging. It is easy to make a diagnosis based on clinical manifestations. Finding of the pathogenic gene may further confirm the diagnosis.
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Objective To explore the clinical study of different frequency repetitive transcranial magnetic stimulation in the treatment of senile schizophrenia.Methods The 70 elderly schizophrenics admitted to Kangning Hospital Affiliated to Wenzhou Medical University from February 2018 to August 2019 were randomly divided into observation group (35 cases) and control group (35 cases).High frequency repetitive transcranial magnetic stimulation was used in the observation group and low frequency repetitive transcranial magnetic stimulation was used in the control group.Both groups were treated for 4 weeks.The changes of clinical global impression (CGI),positive and negative syndrome scale (PANSS),cognitive function rating scale for schizophrenia (SCoRS),scale of social-skills for psychiatric inpatients(SSPI) and serum sex hormone levels before and after treatment were compared between the two groups.Results After treatment,the CGI and PANSS scores of the two groups were lower than those before treatment [observation group:(2.43 ± 0.37) scores vs.(5.61 ± 0.58) scores,(35.73 ± 6.57) scores vs.(79.95 ± 8.98) scores,t =27.346 and 23.512;control group:(3.37 ± 0.48) scores vs.(5.49 ± 0.62) scores,(40.91 ± 8.17) scores vs.(78.64 ± 9.63) scores,t =15.996 and 17.675,P ＜ 0.05];after treatment,the CGI and PANSS scores of the observation group were lower than those of the control group (t =9.176,2.923,P ＜ 0.05).After treatment,the SCoRS scores of the two groups was lower than those before treatment (observation group:t =12.822,control group:t =7.402,P ＜ 0.05);after treatment,the SCoRS score of the observation group was lower than that of the control group [(27.92 ± 5.41) scores vs.(34.25 ± 6.17) scores] (t=4.564,P＜0.05).The SSPI scores of the two groups increased after treatment (observation group:t=9.252;control group:t=3.671,P＜0.05);after treatment,the SSPI scores of the observation group were higher than those of the control group [(35.74 ± 3.27) scores vs.(30.85 ± 2.28) scores](t =7.257,P ＜ 0.05).After treatment,the serum testosterone and prolactin levels in the two groups were higher than those before treatment (observation group:t =13.853,15.198;control group:t =10.075 and 9.225,P ＜ 0.05);after treatment,the serum testosterone and prolactin levels in the observation group were higher than those in the control group (t=5.693 and 7.202,P＜0.05).Conclusions High frequency repetitive transcranial magnetic stimulation is superior to low frequency repetitive transcranial magnetic stimulation in the treatment of senile schizophrenia,and the improvement of sex hormone level is superior to low frequency repetitive transcranial magnetic stimulation,and the improvement of cognitive and social functions is superior to low frequency repetitive transcranial magnetic stimulation.
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OBJECTIVE@#To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology.@*METHODS@#Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database.@*RESULTS@#The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects.@*CONCLUSION@#This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.
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BACKGROUND@#Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1 (HTRA1) gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.@*METHODS@#We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1, 2020. CARASIL probands with genetic diagnosis reported to date were also reviewed. The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.@*RESULTS@#Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included. Compared with typical CARASIL, HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors (P < 0.001), a later onset age (P < 0.001), and a relatively slower clinical progression. Alopecia and spondylosis can be observed, but less than those in the typical CARASIL. Thirty-five heterozygous mutations in HTRA1 were reported, most of which were missense mutations. Amino acids located close to amino acids 250-300 were most frequently affected, followed by these located near 150∼200. While amino acids 250∼300 were also the most frequently affected region in CARASIL patients, fewer mutations precede the 200th amino acids were detected, especially in the Kazal-type serine protease domain.@*CONCLUSIONS@#HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL. The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.
Subject(s)
Humans , Cerebral Infarction , Cerebral Small Vessel Diseases/genetics , Heterozygote , High-Temperature Requirement A Serine Peptidase 1/genetics , Leukoencephalopathies/genetics , Mutation/geneticsABSTRACT
Objective@#To compare the difference of cognitive fusion, empirical avoidance between patients with obsessive-compulsive disorder and healthy control group, and to explore the relationship between obsessive-compulsive score and cognitive fusion, empirical avoidance.@*Methods@#The cognitive fusion questionnaire(CFQ), acceptance and action questionnaire-2nd edition(AAQ-II) and Yale-Brown scale for obsessive-compulsive symptoms (Y-BOCS) were used to investigate 100 subjects with obsessive-compulsive disorder (OCD) and 166 healthy controls.And the differences in cognitive fusion and empirical avoidance scores were compared between the two groups.The relationship of obsessive-compulsive symptoms and cognitive fusion, empirical avoidance was analyzed using multiple linear regression analysis.@*Results@#The scores of cognitive fusion ((49.89±10.62) vs (33.88±11.44), t=-11.345, P<0.01)and empirical avoidance ((29.75±9.53) vs (21.59±7.03), t=-7.995, P<0.01) in obsessive-compulsive disorder group were significantly higher than those in healthy control group.There were significant differences in cognitive fusion and empirical avoidance in age variables (F=8.63, P<0.01). In AAQ-Ⅱ, item 2 (r=0.246, P<0.05), item 6 (r=0.223, P<0.05) and total score (r=0.240, P<0.05) were positively correlated with the total score of Y-BOCS.Item 2 (r=0.311, P<0.01), item 3 (r=0.286, P<0.05), item 6 (r=0.248, P<0.05) and total score (r=0.229, P<0.05) were positively correlated with the scores of obsessive-thinking.In CFQ, item 2 (r=0.231, P<0.0) 5), item 4 (r=0.242, P<0.05), item 7 (r=0.308, P<0.05), item 8 (r=0.277, P<0.05) and item 9 (r=0.249, P<0.05) were positively correlated with the total score of Y-BOCS.Item 8 (r=0.261, P<0.05) was positively correlated with the scores of obsessive-thinking, item 7 (r=0.237, P<0.05) and item 9 (r=0.238, P<0.05) were positively correlated with scores of obsessive-compulsive behavior.When predicting total obsessive-compulsive scores, only CF item 7 of Q (B=1.827, P<0.01), item 3 (B=0.956, P<0.05), and item 6 of AAQ-Ⅱ (B=0.584, P<0.05) entered the equation with a joint explanatory variation of 19%.When predicting the score of obsessive-thinking, only item 2 of AAQ-Ⅱ (B=0.446, P<0.01) entered the equation, explaining the variance was 9.7%.In the prediction of obsessive-compulsive behavior, only item 9 (B=0.815, P<0.05) of CFQ entered the equation, and the explanatory variation was 5.6%.@*Conclusion@#Cognitive fusion in the patients with obsessive-compulsive disorder and the high level of empirical avoidance may be an important factor for the maintenance of the symptoms.
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Objective To compare the difference of cognitive fusion,empirical avoidance between patients with obsessive-compulsive disorder and healthy control group,and to explore the relationship between obsessive-compulsive score and cognitive fusion,empirical avoidance.Methods The cognitive fusion questionnaire(CFQ),acceptance and action questionnaire-2nd edition (AAQ-Ⅱ) and Yale-Brown scale for obsessive-compulsive symptoms (Y-BOCS) were used to investigate 100 subjects with obsessive-compulsive disorder (OCD) and 166 healthy controls.And the differences in cognitive fusion and empirical avoidance scores were compared between the two groups.The relationship of obsessive-compulsive symptoms and cognitive fusion,empirical avoidance was analyzed using multiple linear regression analysis.Results The scores of cognitive fusion ((49.89± 10.62) vs (33.88 ± 11.44),t =-11.345,P＜ 0.01) and empirical avoidance ((29.75±9.53) vs (21.59±7.03),t=-7.995,P＜0.01) in obsessive-compulsive disorder group were significantly higher than those in healthy control group.There were significant differences in cognitive fusion and empirical avoidance in age variables (F=8.63,P＜0.01).In AAQ-Ⅱ,item 2 (r=0.246,P＜ 0.05),item 6 (r=0.223,P＜0.05) and total score (r=0.240,P＜0.05) were positively correlated with the total score of Y-BOCS.Item 2 (r=0.311,P＜0.01),item 3 (r=0.286,P＜0.05),item 6 (r=0.248,P＜0.05) and total score (r=0.229,P＜0.05) were positively correlated with the scores of obsessive-thinking.In CFQ,item 2 (r=0.231,P＜0.0) 5),item 4 (r=0.242,P＜ 0.05),item 7 (r =0.308,P＜ 0.05),item 8 (r =0.277,P＜0.05) and item 9 (r=0.249,P＜0.05) were positively correlated with the total score of Y-BOCS.Item 8 (r=0.261,P＜0.05) was positively correlated with the scores of obsessive-thinking,item 7 (r=0.237,P＜0.05) and item 9 (r=0.238,P＜0.05) were positively correlated with scores of obsessive-compulsive behavior.When predicting total obsessive-compulsive scores,only CF item 7 of Q (B=1.827,P＜0.01),item 3 (B=0.956,P＜0.05),and item 6 of AAQ-Ⅱ (B=0.584,P＜0.05) entered the equation with a joint explanatory variation of 19％.When predicting the score of obsessive-thinking,only item 2 of AAQ-Ⅱ (B=0.446,P＜0.01) entered the equation,explaining the variance was 9.7％.In the prediction of obsessive-compulsive behavior,only item 9 (B=0.815,P＜0.05) of CFQ entered the equation,and the explanatory variation was 5.6％.Conclusion Cognitive fusion in the patients with obsessive-compulsive disorder and the high level of empirical avoidance may be an important factor for the maintenance of the symptoms.
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OBJECTIVE@#To evaluate the efficacy of ultrasound or fluoroscopic-guided percutaneous transluminal angioplasty (PTA) combined with thrombolysis for the treatment of acutely thrombosed arteriovenous fistula (AVF) or grafts (AVG).@*METHODS@#One hundred and ninety-two hemodialysed patients, in whom the thrombosed arterio-venous AVF or AVG developed less than 72 h and there were no contraindications for thrombolysis and PTA, underwent PTA combined with thrombolysis therapy in Sir Run Run Shaw Hospital of Zhejiang University from October 2014 to October 2017. Under ultrasound and/or fluoroscopic guidance, balloon catheter was introduced to thrombosis sites along a guide wire. Then the balloon was inflated and normal saline mixed with urokinase and heparin was injected for thrombolysis. After blood flow was restored, angioplasty was performed on vascular stenosed sites.@*RESULTS@#A total of 274 endovascular interventional operations were performed for 192 patients. The procedure success rate was 98.2%, clinical success rate was 93.8%and complication rate was 1.46%. The post-intervention primary patency rates for AVF group were 87.4%, 76.7%and 63.9%at 3, 6 and 12 months, respectively; while the post-intervention secondary patency rates were 93.7%, 91.6%and 83.0%, respectively. The post-intervention primary patency rates for AVG group were 60.7%, 51.5%and 43.1%at 3, 6 and 12 months, while the post-intervention secondary patency rates were 82.7%, 77.1%and 70.8%, respectively.@*CONCLUSIONS@#PTA combined with thrombolysis is an effective and safe therapeutic option for AVF and AVG thrombosis, which would prolong hemodialysis access and save vascular resources for hemodialyzed patients.
Subject(s)
Humans , Angioplasty , Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Renal Dialysis , Retrospective Studies , Thrombolytic Therapy , Thrombosis , General Surgery , Treatment Outcome , UltrasonographyABSTRACT
OBJECTIVE: To evaluate the effectiveness of semi-open suturation of vaginal stump in preventing pelvic lym-phocele after pelvic lymphadenectomy during gynecologic cancer surgery.METHODS:This study is a retrospectivestudy.Totally 348 patients with cervic cancer or endometrial cancer who underwent pelvic lymphadenectomy and/or para-aortic lymphadenectomy from January 2012 to September 2018 were divided into two groups according to the suturationof vaginal stump:102 patients were in the semi-open group and 246 patients were in the closed group.The two groupswere compared concerning the surgery time,harvested lymph node,drainage time,albumin level,hemoglobin content,and the incidence of lymphocele and symptomatic lymphocele.RESULTS:There were no differences between two groupswith respect to surgery time,harvested lymph node,drainage time,albumin level or hemoglobin content(P>0.05).Theincidence of lymphocele and symptomatic lyphocele in semi-open group was significantly lower than that in closed group(35.3%versus79.3%,3.9%versus19.5%,P<0.05);the average diameter of lymphocele in semi-open group was also sig-nificantly lower than that in closed group(4.1cm versus 5.9cm,P<0.05).CONCLUSION:The result of this study indicatesthat the application of semi-open saturation of vaginal stump is an effective way to reduce the incidence of pelvic lym-phocele after gynecologic malignancy,which is simple and with reliable effect.It doesn′t increase the incidence of postop-eration complications and deserves clinical application.
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OBJECTIVE: To investigate the clinical efficacy of cervicectomy for cervical intraepithelial neoplasia(CIN)in patients with cervicovaginal shortening.METHODS: Retrospectively analyze the clinical data of the 120 cases of CIN treated in Shengjing Hospital of China Medical University from April 2014 to November 2018.Cervicectomy was performed because of cervicovaginal shortening caused by menopausal or peri-menopausal cervical atrophy or cervical surgery.The clinical treatment,efficacy and prognosis of the patients were reviewed.RESULTS: The mean age of the 120 patients was 55.2 years(range:35-77 years).The indications of operation included:persistent abnormal cervical cytology test(7),CIN2(42),CIN3(70),squamous carcinoma of the cervix(1);peri-menopausal and menopausal patients with obvious cervicovaginal atrophy(100),premenopausal patients with natural short cervix(2),and obvious cervicovaginal shortening caused by cervical surgery(18).The mean operating time was 23.2 min(range 10-30 min),the mean bleeding volume was 7.8 mL(range:5-20 mL),and the mean height of cervix resected was 2.59 cm(range:2-3 cm).No secondary injury,bleeding or other postoperative complications occurred during surgery;cervical postoperative wounds healed well;only one case developed cervical adhesion after surgery.The postoperative histologic diagnosis were compared with the preoperative histologic diagnosis,in which 45 degraded(37.50%),42 consistent(35.00%),and 33 upgraded(27.50%).HPV conversion rate 3 months after cervicectomy was 80.81%(80/99),and total HPV conversion rate was 88.89%(88/99).A total of 29 patients underwent secondary surgery,23 underwent total hysterectomy,and 6 underwent extensive hysterectomy and pelvic lymphadenectomy.All patients were followed up,once every 3 to 6 months,and median follow-up time was 29.5 months(range 4-59 months).All patients recovered well after surgery;only 2 cases showed positive margins,and only 2 cases of residual disease and 1 case of recurrence were found during follow-up.CONCLUSION: For patients with cervical intraepithelial neoplasia of cervicovaginal shortening,cervicectomy is a safe,effective and relatively microinvasive treatment.