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Electrocatalytic CO2 reduction (CO2RR) to alcohols offers a promising strategy for converting waste CO2 into valuable fuels/chemicals but usually requires large overpotentials. Herein, we report a catalyst comprising unique oxygen-bridged Cu binuclear sites (CuOCu-N4) with a Cu···Cu distance of 3.0-3.1 Å and concomitant conventional Cu-N4 mononuclear sites on hierarchical nitrogen-doped carbon nanocages (hNCNCs). The catalyst exhibits a state-of-the-art low overpotential of 0.19 V (versus reversible hydrogen electrode) for ethanol and an outstanding ethanol Faradaic efficiency of 56.3% at an ultralow potential of -0.30 V, with high-stable Cu active-site structures during the CO2RR as confirmed by operando X-ray adsorption fine structure characterization. Theoretical simulations reveal that CuOCu-N4 binuclear sites greatly enhance the C-C coupling at low potentials, while Cu-N4 mononuclear sites and the hNCNC support increase the local CO concentration and ethanol production on CuOCu-N4. This study provides a convenient approach to advanced Cu binuclear site catalysts for CO2RR to ethanol with a deep understanding of the mechanism.
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Euglycemic diabetic ketoacidosis(euDKA)is a rare acute metabolic disorder syndrome,its characteristics include metabolic acidosis with a high anion gap,positive ketones in blood or urine,and blood glucose<13.9 mmol/L.Due to low blood sugar level,euDKA is easy to be missed or delayed treatment in clinical work,resulting in serious consequences.In recent years,many cases of euDKA have been reported,but its inducements and pathogenesis are not fully understood.This article reviews the common inducements and pathogenesis of euDKA.
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Objective To conduct a comparative analysis of the biomechanical characteristics of the lower limbs during stair descent in patients with hemiplegia using different method to provide theoretical references for reducing fall risk during stair descent.Methods Ten healthy subjects and 20 patients with hemiplegia were selected,and their kinematic and dynamic data during stair descent were collected using the Qualisys Motion capture system and the Kistler three-dimensional dynamometer.Their biomechanical characteristics and fall risks were also analyzed.Results Compared with that of healthy subjects and patients that step on the healthy side(SHS),the range of motion(ROM)of the affected side in the lower-limb joints of patients that step on the affected side(SAS)was smaller.SHS reduced the flexion and extension ranges of the healthy side of the knee joint,and the ROM of the affected side in the lower-limb joints of SHS patients was greater than that of SAS patients.The ground reaction force(GRF)curve changes of SAS patients in left and right directions during stair descent were relatively consistent with those of normal subjects.The maximum vertical GRF of the affected side in SAS patients at the moment of landing was 1.05 times the body weight,whereas that of the healthy side was 1.25 times the body weight,which was lower than that of normal subjects(1.5 times the body weight).The maximum vertical GRF of the healthy side in SHS patients at the moment of landing was 1.85 times the body weight,which was higher than that of SAS patients and normal subjects.Conclusions Compared with that of SAS patients,the affected limb side of SHS patients has a greater ROM and vertical GRF at the moment of landing during stair descent,making SHS difficult to master.SAS is most consistent with the biomechanical characteristics during stair descent of patients with hemiplegia.
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In the quality control of Chinese medicine, the detection of active components and toxic and harmful components are two important links. Although conventional methods such as high performance liquid chromatography and liquid chromatography-mass spectrometry can accurately quantify the above substances, they have shortcomings such as complicated operation, high costs, inability of detection at any time, difficult detection of insoluble and macromolecular substances. Enzyme-linked immunosorbent assay (ELISA) can adsorb antigens or antibodies on the surface of solid carriers and realize qualitative or quantitative analysis of targets by using the specific reactions of antigens and antibodies. This method is praised for the simple operation, high sensitivity, strong specificity, simple requirements for experimental equipment, a wide application range, and low costs. In recent years, ELISA has been widely used in the quality control of Chinese medicine, especially in the content determination of mycotoxins represented by aflatoxin and the qualitative and quantitative analysis of active components. ELISA plays an increasingly important role with its unique advantages, providing new methods and ideas for the rapid quality examination of large quantities of Chinese medicines. This paper reviews the research progress in ELISA for the quality control of Chinese medicine in recent years and prospects its technical development and application prospects, aiming to provide reference and research ideas for further using this method to ensure the quality, safety, and controllability of Chinese medicine.
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Objective:To investigate the value of age shock index (Age-SI) in predicting rebleeding and death in patients with liver cirrhosis complicated with acute portal vein thrombosis treated by transjugular intrahepatic portosystemic shunt (TIPS).Methods:A total of 134 patients with liver cirrhosis complicated with acute portal vein thrombosis treated in West China Hospital of Sichuan University from April 2019 to April 2021 were selected, all patients were treated with TIPS, the differences of clinical data between rebleeding and no rebleeding, death and survival were observed and analyzed.Results:The age, child Pugh grade C ratio, Age-SI and neutrophil lymphocyte ratio (NLR) of patients with rebleeding were (57.28±9.92)years, 42.11%, (54.68±7.8) and (4.40±0.92), respectively, which were significantly higher than those of patients without rebleeding ( P<0.05). The age of dead patients, the course of liver cirrhosis, Age-SI and NLR were (59.90±9.81)years, (60.86±9.82)months, (55.47±7.64) and (4.76±0.99), respectively, which were significantly higher than those of surviving patients ( P<0.05). Logistic regression analysis showed that age, Age-SI and NLR were the influencing factors of rebleeding ( P<0.05), and Age, course of liver cirrhosis and Age-SI were the influencing factors of death ( P<0.05). The area under the receiver operating characteristic (ROC) curve for predicting rebleeding by Age-SI was 0.862( P<0.05); The area under the ROC curve for predicting death by Age-SI was 0.854 ( P<0.05). Conclusions:Age-SI has high application value in predicting rebleeding and death in patients with liver cirrhosis complicated with acute portal vein thrombosis treated with TIPS, which is worthy of further study.
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Objective:To explore the relation among self-esteem, psychological flexibility and mental health in medical students, and to provide scientific reference for mental health education for medical students.Methods:A total of 788 medical students selected from a medical university in Chongqing City were investigated with the symptom checklist 90 (SCL-90), self-esteem scale (SES), acceptance and action questionnaire-Ⅱ (AAQ-Ⅱ), and cognitive fusion questionnaire-fusion (CFQ-F). SPSS 22.0 software was used for statistical analysis. T test, ANOVA, correlation analysis and tests for mediation effects were conducted. Results:There were significant differences in self-esteem and mental health level among medical students in gender and different grades ( t=-2.55, P<0.05; F=6.53, P<0.05). Mental health, self-esteem and psychological flexibility of medical students were correlated in pairs ( r=-0.528-0.694, P<0.01). Psychological flexibility played a partial mediation role between self-esteem and mental health of medical students, and the mediating effect accounted for 60.03% of the total effect. Conclusion:Self-esteem can directly predict the mental health of medical students, and can also indirectly affect mental health through psychological flexibility. Medical universities should carry out psychological education and promotion work with pertinence.
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ObjectiveTo investigate the protective effect and regulatory mechanism of berberine (BBR) against the senescence of ovarian granulosa cells. MethodA cell senescence model in the human ovarian granulosa-like tumor (KGN) cell line was induced by H2O2. A control group, a model group, and high-dose (1 μmol·L-1) and low-dose (0.5 μmol·L-1) BBR groups were set up. The cells in the model group and the BBR groups were incubated with 10 μmol·L-1 H2O2 for 40 min. The effect of BBR on KGN cell proliferation was detected by cell counting kit-8 (CCK-8) assay. The effect of BBR on the senescence of KGN cells was detected by β-galactosidase staining. The effects of BBR on the apoptosis and ROS content of KGN cells were detected by flow cytometry. The effects of BBR on the mRNA expression of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax), cysteinyl aspartate-specific protease-3 (Caspase-3), forkhead transcription factor O1 (FoxO1), and catalase (CAT) was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Western blot was used to detect the effects of BBR on protein expression of silent information regulator1 (SIRT1), superoxide dismutase 2 (SOD2), c-Jun N-terminal kinase (JNK), FoxO1, autophagy-associated protein microtubule-associated protein light chain 3Ⅱ (LC3BⅡ), mammalian ortholog of yeast Atg6 (Beclin-1), and ubiquitin-binding protein p62. ResultAfter H2O2 induction for 40 min, the cell proliferation rate of the model group decreased compared with that of the control group (P<0.01), and the cell proliferation rates of the BBR groups increased compared with that of the model group (P<0.05). The results of β-galactosidase staining showed that the cells of the model group showed significant senescence compared with those of the control group (P<0.01), and the cellular senescence in the BBR groups was reduced compared with that of the model group (P<0.01). As revealed by flow cytometry, compared with the control group, the model group showed increased apoptosis rate (P<0.01), and compared with the model group, BBR groups showed decreased apoptosis rates (P<0.05). Meanwhile, the ROS content in the model group increased compared with that in the control group (P<0.01), and compared with the model group, the BBR groups showed reduced cellular ROS content (P<0.01). The Real-time PCR results showed that compared with the control group, the model group showed decreased mRNA expression of CAT and Bcl-2/Bax in KGN cells and increased mRNA expression of Caspase-3 and FoxO1 (P<0.05), and compared with the model group, the BBR groups showed increased mRNA expression of CAT and Bcl-2/Bax (P<0.05) and reduced mRNA expression of Caspase-3 and FoxO1 in KGN cells (P<0.05). As revealed by Western blot results, SIRT1, SOD2, and p62 protein levels decreased in the model group compared with those in the control group (P<0.01), and JNK FoxO1, LC3BⅡ, and Beclin-1 protein levels increased (P<0.05). After BBR intervention, SIRT1, SOD2, and p62 protein levels increased (P<0.01), and JNK, FoxO1, LC3BⅡ, and Beclin-1 protein levels decreased compared with those in the model group (P<0.05). ConclusionBBR has an inhibitory effect on ovarian granulosa cell senescence, and the mechanism is related to the inhibition of apoptosis and autophagy mediated by the SIRT1/FoxO1 pathway.
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ObjectiveTo understand the situation of nosocomial infection in cancer hospitals and its changing trend, so as to provide a basis for adjusting the focus of nosocomial infection prevention and control in cancer hospitals. MethodsData of nosocomial infection quality control indices of Sun Yat-sen University Cancer Center from 2019 to 2021 were obtained through the nosocomial infection monitoring system, and the changes of these indices across the three years were analyzed by Chi-square test and Cochran-Armitage trend test. ResultsFrom 2019 to 2021, the incidence rates of nosocomial infection in this hospital were 0.80%, 0.78% and 0.57%, which decreased significantly year by year (P<0.001). Among them, surgical site and respiratory system infection were more common, accounting for 35.75% and 31.08%, respectively. Gram-negative bacteria and fungi were the main pathogens. The incidence rate of multidrug-resistant bacteria in hospital increased year by year, from 0.08‰ to 0.14‰ (P<0.001), among which methicillin-resistant staphylococcus aureus, carbapenem-resistant Enterobacter and bacteria producing ultra-broad spectrum β-lactamase (ESBLs) bacteria increased significantly. The incidence rates of three-tube associated infections were no different across 3 years (P>0.05), which were still at high levels. ConclusionFrom 2019 to 2021, the prevention and control of nonsocomial infection in the cancer hospital has been improved overall. Meanwhile, the infections of respiratory system and surgical sites, ESBLs related multidrug-resistant bacteria and three-tube are weak links in cancer specialized hospitals, which need to be emphasized and improved.
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Based on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway, this study investigated the effect of medicated serum of Sparganii Rhizoma(SR) and Curcumae Rhizoma(CR) on the proliferation, apoptosis, migration, and secretion of inflammatory factors of ectopic endometrial stromal cells(ESCs). Specifically, human ESCs were primary-cultured. The effect of different concentration(5%, 10%, 20%) of SR-, CR-, and SR-CR combination-medicated serum, and AG490 solution(50 μmol·L~(-1)) on the proliferation of ESCs was detected by methyl thiazolyl tetrazolium(MTT) assay, and the optimal dose was selected accordingly for further experiment. The cells were classified into normal serum(NS) group, SR group(10%), CR group(10%), combination(CM) group(10%), and AG490 group. The apoptosis level of ESCs was detected by flow cytometry, and the migration ability was examined by wound healing assay. The secretion of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α was determined by enzyme-linked immunosorbent assay(ELISA). The protein levels of cysteinyl aspartate specific protei-nase-3(caspase-3), B-cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) and the levels of phosphorylated(p)-JAK2 and p-STAT3 were detected by Western blot. The results showed that the viability of ESCs cells was lowered in the administration groups compared with the blank serum group(P<0.01), especially the 10% drug-medicated serum, which was selected for further experiment. The 10% SR-medicated serum, 10% CR-medicated serum, and 10% CM-medicated serum could increase the apoptosis rate(P<0.01), up-regulate the protein expression of caspase-3 and Bax in cells(P<0.05 or P<0.01), down-regulate the expression of Bcl-2(P<0.01), decrease the cell migration rate(P<0.05 or P<0.01), and reduce the secretion levels of IL-1β, IL-6, and TNF-α(P<0.05 or P<0.01), and levels of p-JAK2 and p-STAT3(P<0.05 or P<0.01). Compared with the SR and CR groups, CM group showed low cell viability(P<0.01), high protein expression of caspase-3 and Bax(P<0.05 or P<0.01), and low protein expression of Bcl-2 and p-JAK2(P<0.05). After incubation with CM, the apoptosis rate was higher(P<0.05) and the migration rate was lower(P<0.01) than that of the CR group. The p-STAT3 protein level of CM group was lower than that of the RS group(P<0.05). The mechanism of SR, CR, and the combination underlying the improvement of endometriosis may be that they blocked JAK2/STAT3 signaling pathway, inhibited ESC proliferation, promoted apoptosis, weakened cell migration, and reduced the secretion of inflammatory factors. The effect of the combination was better than that of RS alone and CR alone.
Subject(s)
Female , Humans , Janus Kinase 2 , Caspase 3 , bcl-2-Associated X Protein , Interleukin-6/genetics , Apoptosis , Signal Transduction , Cell Proliferation , STAT3 Transcription Factor/geneticsABSTRACT
OBJECTIVE@#To explore the clinical and genetic characteristics of a child with spinocerebellar ataxia type 29 (SCA29) due to novel variant of the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) gene.@*METHODS@#The child was subjected high-throughput sequencing, and candidate variant was verified by Sanger sequencing of his family members.@*RESULTS@#The child was found to harbor a c.800C>T (p.T267M) variant of the ITPR1 gene, which was not found in his parents and their fetus. The variant has occurred in a hotspot of the ITPR1 gene variants and was unreported before in China. Based on his clinical and genetic characteristics, the child was diagnosed with SCA29.@*CONCLUSION@#The novel heterozygous c.800C>T (p.T267M) of the ITPR1 gene probably underlay the SCA29 in this child.
Subject(s)
Child , Humans , Family , Inositol 1,4,5-Trisphosphate Receptors/genetics , Mutation , Spinocerebellar Ataxias/genetics , Spinocerebellar DegenerationsABSTRACT
OBJECTIVE To study the repair effect and mechanism of Zhixu burn ointment on deep second-degree burned model rats. METHODS The deep second-degree burned model was established with a temperature-controlled apparatus. The model rats were randomly divided into model group, Jingwanhong ointment group and Zhixu burn ointment high-dose, medium-dose and low-dose groups (specifications were 20 g core+20 mL wetting agent, 10 g core+20 mL wetting agent, 5 g core+20 mL wetting agent, respectively). Another blank control group (only dehairing treatment, no modeling) was set up, with 10 rats in each group. The rats in each administration group were given corresponding drugs, the rats in the blank control group were not treated, and the rats in the model group were given normal saline once a day for 21 d. The healing of burn wounds and histomorphological changes of burned skin in each group of rats were observed, and the healing rate of wounds was calculated; the levels of vascular endothelial growth factor (VEGF), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α(TNF-α) in the wound skin tissue of rats were detected by enzyme-linked immunosorbent assay; immunohistochemical method was used to detect the expression levels of VEGF and platelet endothelial cell adhesion molecule-1 (CD31) protein in burned skin tissue. RESULTS Compared with model group, the wound area of the rats in the Jingwanhong ointment and Zhixu burn ointment groups gradually decreased and healed significantly by day 21, and the wound healing rate was significantly higher (P<0.05 or P<0.01); thicker new epidermal layer was seen in the skin tissue, and connective tissue and new blood vessels were significantly increased in the dermis; the expression levels of IL-1β, IL-6 and TNF-α were significantly decreased (P<0.05 or P<0.01), and the expression levels of VEGF and CD31 protein were significantly increased (P<0.05 or P<0.01) in the burned skin tissue. CONCLUSIONS Zhixu burn ointment can repair the skin of deep second-degree burned model rats, and the mechanism may be related to reducing the inflammatory response of burn wound and promoting the angiogenesis.
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Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.
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Humans , Adult , Cardiac Surgical Procedures/methods , Cardiomyopathy, Hypertrophic/genetics , Echocardiography , Electrocardiography , Phenotype , Sarcomeres/geneticsABSTRACT
Objective: To evaluate the efficacy and prognosis of orthopedic surgical resection surgery in patients with newly diagnosed multiple myeloma (NDMM). Methods: This retrospective cohort study collected clinical data of patients with NDMM who underwent surgery due to spinal cord compression or pathological long-bone fractures at the Peking Union Medical College Hospital from 1 January 2003 to 31 December 2021. Patients who received biopsy or vertebroplasty/kyphoplasty were excluded and patients with the same degree of bone disease and who did not undergo any surgical intervention were selected as controls. Visual analogue scale (VAS) and physical status (ECOG) scores, progression-free survival (PFS), and overall survival (OS) were compared. Statistical analysis included the χ2-test, t-test, and Kaplan-Meier methods. Results: Baseline data were compared between the surgical group (n=40 with 43 interventions) and the non-surgical group (n=80), and included sex, age, paraprotein type, International Staging System (ISS), number of lytic lesions, cytogenetic abnormalities, first-line treatment, and the proportion of patients receiving autologous stem cell transplantation (ASCT) (all P>0.05). Serum M protein levels in the surgical group were significantly lower than those of the non-surgical group [(21.95±16.44) g/L vs. (36.18±20.85) g/L, P=0.005]. The surgical lesions involved the axial skeleton (79.1%, 34/43) or the extremities (20.9%, 9/43). VAS and ECOG scores improved significantly after surgery (VAS: 2.30±0.80 vs. 6.60±1.50, P<0.001; ECOG: 2.09±0.59 vs. 3.09±0.73, P<0.001). The median follow-up time was 51 months. Kaplan-Meier survival analysis suggested that the median PFS (25 vs. 29 months) and OS (46 vs. 60 months) were comparable between the surgical and non-surgical intervention groups (both P>0.05). Subgroup analysis showed that among patients with ISS Ⅰ or those who had received ASCT, PFS in the surgical group was similar to that of the non-surgical intervention group (both P>0.05), while OS was worse (P=0.005, 0.017). Patients with ISS Ⅱ/Ⅲ scores or without ASCT had similar PFS and OS between the surgical and non-surgical intervention groups (all P>0.05). Cox multivariate analysis suggested that ISS and ASCT were independent prognostic factors for OS (ISS: HR=0.42, 95%CI 0.19-0.93, P=0.031; ASCT: HR=0.41, 95%CI 0.18-0.97, P=0.041), while orthopedic surgery did not influence survival (P=0.233). Conclusion: For patients with NDMM, orthopedic surgical resection decreased bone-related complications and improved quality of life, but did not affect survival.
Subject(s)
Humans , Prognosis , Multiple Myeloma/diagnosis , Hematopoietic Stem Cell Transplantation/methods , Retrospective Studies , Quality of Life , Transplantation, Autologous , Orthopedic Procedures , Treatment OutcomeABSTRACT
OBJECTIVE@#Acetaminophen (APAP) overdose is a common cause of liver injury. This study aimed to investigate the protective effect of honokiol (Hon) against APAP-induced hepatotoxicity and its potential mechanism.@*METHODS@#C57BL/6 mice were administrated with Hon (10 and 30 mg/kg) after APAP (300 mg/kg) treatment. On 1.5 h and 5 h after Hon treatment, mice were sacrificed. Serum and liver were collected. And then, liver injury-related indexes, APAP metabolism-related indexes, mitochondrial respiratory chain function-related indexes, and mitochondrial membrane function-related protein expression were evaluated.@*RESULTS@#It was found that Hon significantly decreased serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity and glutathione (GSH) depletion, increased hepatic catalase (CAT) and GSH peroxidase (GSH-Px) activities, reduced hepatic MDA and 3-nitrotyrosine contents, inhibited hepatic CYP1A2 activity and APAP protein adducts (APAP-CYS) formation. Meanwhile, oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased, whereas the release of H2O2 in the mitochondria was decreased following Hon treatment. Furthermore, Hon markedly down-regulated p-JNK in both cytosol and mitochondria, and obviously inhibited the release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from mitochondria to cytosol.@*CONCLUSION@#Hon alleviated APAP-induced liver injury through the following pathways: Reducing the production of APAP-CYS by inhibiting CYP1A2 activity; Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT, GSH-Px and GSH; Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV; Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria, thereby reducing the release of AIF and EndoG.
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Objective To investigate the expression levels of HBV pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in circulating serum of chronic hepatitis B (CHB) patients after withdrawal from nucleos(t)ide analogues (NUC), as well as the correlation of HBV pgRNA and HBcrAg levels in circulating blood in different periods of time with recurrence in CHB patients after drug withdrawal. Methods Among the patients who attended the outpatient service of Affiliated Hospital of North Sichuan Medical College from December 2019 to July 2022, a total of 108 CHB patients who received anti-HBV therapy for at least 5 years and met the criteria for drug withdrawal in 2017 EASL Guidelines were enrolled. According to the time of drug withdrawal, the patients were divided into 4-, 12-, and 24-week groups after drug withdrawal, and according to the presence or absence of recurrence, they were divided into recurrence group and non-recurrence group. Quantitative real-time PCR was used to measure the level of HBV pgRNA in circulating serum of CHB patients; ELISA was used to measure the expression level of HBcrAg in peripheral venous blood; quantitative real-time PCR was used to measure HBV DNA load with high accuracy. The t -test was used for comparison of continuous data between two groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Pearson correlation test was used to investigate the correlation between the indices in circulating blood. Results For the CHB patients after drug withdrawal, the recurrence rate was 17.1% at 4-12 weeks, cumulative recurrence rate reached 29.3% after 24 weeks of follow-up, the patients with positive HBV DNA alone accounted for 64.3% and 60.0%, respectively, those with positive HBeAg alone accounted for 28.5% and 20.0%, respectively, and those with positive HBV DNA and HBeAg accounted for 7.1% and 20.0%, respectively. The expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum of CHB patients at 24 weeks after drug withdrawal were significantly higher than those at the time of drug withdrawal and at 4 weeks after drug withdrawal, and there was a significant difference between groups at different time points (all P 0.05). Conclusion The recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg than the non-recurrence group at the time of drug withdrawal, suggesting that the levels of HBV pgRNA and HBcrAg in the CHB patients of the non-recurrence group at the time of drug withdrawal may be used as the reference thresholds for safe drug withdrawal in CHB patients, and measurement of HBV pgRNA and HBcrAg may be one of the potential reference indicators for the selection of anti-HBV treatment endpoints in the future.
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Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.
Subject(s)
Female , Male , Humans , Child , Adolescent , Prospective Studies , Nephritis, Hereditary , Proteinuria/drug therapy , Serum AlbuminABSTRACT
Aim To study the effeet of Wenyang Hua- Nrpl signaling pathway in systemic sclerosis ( SSc ) zhuo Tongluo formula ( WYHZTLF) on the Sema3A/ mouse model, and to explore its mechanism in the treatment of SSe.Methods The systemic sclerosis mouse model was constructed and divided into control group, model group, WYHZTLF low (21 g • kg 1 ) , medium (42 g • kg 1 ) , high (84 g • kg 1 ) dose group and the Sema3A inhibitor epigallocatechol gallate (EGCG) group.All groups were given intragastric administration for four weeks, and the control and model groups were treated with saline.Histopathology and dermal thickness were detected by HE, VEGFA pro-tein expression levels were detected by immunohisto- chemistry; the protein expression levels of Sema3A, Nrpl and VEGFA were determined by Western blot; Sema3A expression levels in mouse serum were detec-terl by ELISA.Results Comparer] with model group, WYHZTLF significantly alleviated the skin lesions in systemic sclerosis mouse model, significantly inhibited the dermal thickness, inhibited the protein expression levels of VEGFA, Sema3A and Nrpl , and reduced the expression levels of serum Sema3A.Conclusion WYHZTLF can improve the vascular injury of SSc, and its mechanism may be related to the inhibition of VEGFA and Sema3A/Nrpl signaling pathway.
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Objective To establish a method of in vivo microvascular imaging and blood flow calculation with better continuous imaging quality. Methods Anesthetized mice with dye injection through tail vein were placed in the center of a 37 ℃ hot plate holder. The stripped tissues were placed in a self ̄made low edge confocal dish and immersed in normal saline. The exposed tissues were pressed with self ̄made circular metal pads of different weights and sizes. The microvascular blood flow in the liver and hind limb of pregnant mice (n = 3) and normal female mice (n = 3) were measured by the improved device. Results This method can accomplish stable and continuous imaging. The blood flow velocity of liver and hind limb of pregnant mice were faster than that of normal female mice. Conclusion This method can be used for three ̄dimensional imaging of microvessels and detection of blood flow velocity in organs.
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Objective:To analyze the rules of medication and principles of formulas for the treatment of coronavirus disease 2019 (COVID-19) using the traditional Chinese medicine inheritance support platform (V2.5).Methods:The clinical data, including gender, age, clinical symptoms, frequency of traditional Chinese medicine medication and prescription information, of patients with COVID-19 and asymptomatic infection who were admitted to Hebei COVID-19 designated hospital supported by medical team of First Affiliated Hospital of Hebei University of Chinese Medicine from January to March 2021 were collected. The information data were input into the traditional Chinese medicine inheritance support platform (V2.5). The data mining and analysis were realized by the integrated association rules and complex entropy clustering analysis methods of the software, including the analysis of the frequency of each drug use, drug meridian, taste, and prescription rules, and the new prescriptions were developed.Results:A total of 564 patients (564 prescriptions) were enrolled, involving 200 Chinese herbs, including 357 cases of common COVID-19 and 207 cases of asymptomatic infection. The proportion of women with common COVID-19 was high, and the high incidence age group was 51-70 years old. There was no significant difference in gender of asymptomatic infection, and the high incidence age group was 1-20 years old. The main clinical manifestations of most patients were head heavy and cough, followed by low fever and cough with sputum, the main tongue coating and pulse pattern were similar in both types of patients. The frequency of traditional Chinese medicine used in patients with common type of COVID-19 from high to low was liquorice root (326 times), indian bread (264 times), pinellia tuber (263 times), bitter apricot seed (236 times), baical skullcap root (229 times), gypsum (205 times), agastache rugosus (201 times), dried tangerine peel (194 times), ephedra (184 times), and Chinese thorowax root (163 times), while that used by asymptomatic infection were baical skullcap root (174 times), liquorice root (142 times), medicated leaven (137 times), agastache rugosus (127 times), pinellia tuber (114 times), Chinese thorowax root (100 times), officinal magnolia bark (91 times), atractylodes rhizome (89 times), peony root (84 times), and milkvetch root (83 times). The two types of patients were mainly treated with warm, cold and flat drugs, and the nature and taste were mainly pungent, bitter and sweet. The meridian tropism of drugs was mainly lung, spleen and stomach. High frequency drug formulation mainly included drugs for resolving turbidity and detoxification. At the same time, seven new prescriptions for common COVID-19 and four new prescriptions for asymptomatic infection were developed.Conclusions:The primary reason for the COVID-19 occurrence and development is turbidity-toxin and the qi of plague, and resolving turbidity and detoxication are the basic treating principle. On the basis, for patients with common COVID-19, symptomatic treatment such as relieving exterior syndrome, clearing heat, resolving phlegm, and antitussive drugs should be taken into account at the same time, while the treatment of asymptomatic infections should focus more on supporting the body and eliminating the harmful pathogens.
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The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.