ObjectiveTo explore the potential mechanism of Erchen Decoction （二陈汤， ECD） in improving metabolic syndrome （MS） with phlegm syndrome. MethodsForty mice were randomly divided into a blank group of 10 mice and a modeling group of 30 mice. The MS model with phlegm syndrome was induced in the modeling group by high-fat diet. Thirty successfully modeled mice were randomly divided into a model group， a ECD group， and a metformin group， with 10 mice in each group. The ECD group was given 0.4 g/（kg·d） of ECD， while the metformin group was intervened with 11.1 g/（kg·d） of metformin solution， and the blank group and the model group were given 0.02 ml/（g·d） of sterilized drinking water， all by gavage， once daily for 4 weeks. Body weight， abdominal circumfe-rence， body length， Lee's index and food intake were recorded. Blood glucose and blood lipid levels including fasting blood glucose， triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. ELISA was used to detect serum leptin levels， while HE staining was used to observe liver pathological changes. Western Blot and q-PCR were used to detect protein and mRNA expression of hypothalamic leptin receptor （LepR）， pro melanocortin （POMC）， and neuropeptide Y （NPY） in the hypothalamus. Immunofluorescence was used to detect fluorescence expression of POMC and NPY in the hypothalamic arcuate nucleus region. ResultsPathological results showed that the mice in the model group had numerous fat vacuoles in hepatocytes and significant liver fat deposition， while the ECD and metformin groups showed reduced fat vacuoles and less liver fat deposition. Compared to those in the blank group， the mice in the model group mice showed liver fat deposition， increased body weight， abdominal circumference， Lee's index and food intake； fasting blood glucose， TG， TC， LDL-C， and serum leptin levels were elevated， while HDL-C was decreased； the expression of LepR， POMC protein levels and their mRNA expression decreased， while the protein level and mRNA expression of NPY increased； the fluorescence expression of POMC in the arcuate nucleus was reduced， while NPY fluorescence expression increased （P＜0.05 or P＜0.01）. Compared to the model group， the ECD group and metformin group showed significant improvements in the above indicators （P＜0.05 or P＜0.01）. Compared to the ECD group， the metformin group showed a reduction in body weight and NPY fluorescence expression， and an increase in HDL-C levels （P＜0.05 or P＜0.01）. ConclusionECD can downregulate serum leptin levels and improve glucose and lipid metabolism in the MS of phlegm syndrome. Its mechanism of action may be to reduce liver fat deposition and thereafter affect the expression of neuropeptides related to feeding activity in the hypothalamus.

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To explore the mechanism of Buzhong Yiqi Decoction in the treatment of retinitis pigmentosa (RP) based on network pharmacology; To verify it by in vitro experiments.Methods:The effective active components and corresponding targets of Buzhong Yiqi Decoction were screened by retrieving TCMSP database, and the RP-related targets were obtained by searching GeneCards, OMIM and other databases. The interaction network diagram of Buzhong Yiqi Decoction-RP was drawn by Cytascape3.7.1 software, and the core targets were extracted. DAVID online database was used to enrich and analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway; the FerrDb database was searched to obtain the genes that regulate ferroptosis, and finally comprehensively analyze the relationship between the active targets of Buzhong Yiqi Decoction, RP and ferroptosis and make predictions; finally, molecular docking was performed by Auto Dock software to verify the reliability of the results. In vitro experiment, rat Muller cells were used as the research object, and LPS-induced cells were used to construct model cells in vitro. The blank group, model group, Buzhong Yiqi Decoction low-, medium- and high-dosage groups were set up, and the cell proliferation was detected by CCK-8 method; the concentrations of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) and ferroptosis in the cells were detected by the kit method; the expressions of HIF-1α MRNA and GPX-4, FTH-1, ACSL4 mRNA levels in cells of each group were detected by RT-PCR.Results:Totally 117 effective targets were selected from Buzhong Yiqi Decoction, and IL-6, IL-1β, EGFR, ESR1, PPARG may be the targets of Buzhong Yiqi Decoction in regulating ferroptosis and anti-RP. Buzhong Yiqi Decoction could regulate ferroptosis by mediating MAPK, HIF-1, TNF, AGE-RAGE, Toll-like receptor, IL-17, PI3K-Akt and other signal pathways. Molecular docking virtual results suggested that the quercetin, kaempferol, β-Sitosterol and IL-6, IL-1β, EGFR, ESR1, PPARG and other candidate core targets had good binding activity. Compared with the model group, the cell activity, level of SOD, LDH activity, MDA content and Fe 3+ content, IL-6 mRNA, HIF1A mRNA ,ACSL4 mRNA in each Buzhong Yiqi Decoction group significantly decreased ( P<0.05), the expressions of GPX-4 and FTH-1mRNA significantly increased ( P<0.05). Conclusion:Buzhong Yiqi Decoction may play the role of anti-inflammation and anti-ferroptosis through multiple components, multiple targets and multiple molecular pathways, thus achieving the effect of prevention and treatment of RP.

Objective To analyze the epidemiological burden of glaucoma in China based on data from the Global Burden of Disease 2019(GBD 2019)database to provide a theoretical basis for the prevention and control of glaucoma in China.Methods Analysis of the glaucoma epidemic trend and age,period,and gender trends in China from 1990 to 2019 and the correlation between glaucoma and the Socio-Demographic Index(SDI)were conducted according to relevant data on the number of patients,prevalence,disability-adjusted life years(DALYs)and DALY rates downloaded from the GBD 2019 database.Results In 2019,China was ranked globally first for the number of people with glaucoma and second for DALYs due to glaucoma.In 2019,China's glaucoma prevalence was among the highest globally,with the number of pa-tients being 1.92 times that of 1990.Both the prevalence and the DALY rate demonstrated a persistent upward trajectory.The demographic distribution of patients with glaucoma in China revealed a curve which peaked among middle-aged individ-uals,with higher prevalence observed in males than females.An inverse correlation was identified between SDI and the age-standardized prevalence and DALY rates,which exhibited a negative average annual percentage change,indicative of a pro-gressive decline with rising SDI.Conclusion From 1990 to 2019,China experienced a significant increase in the burden of glaucoma,ranking among the highest globally,with a positive correlation observed between the disease burden and the level of social development.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

OBJECTIVE To identify the influence factors associated with 28-day fatality among COVID-19 hospitalizations and to analyze the interaction between the disease severity at admission and the use of hospital preparations.METHODS A retrospective review of records from COVID-19 hospitalizations aged 18 to 90 who were admitted to the Jiangsu Province Hospital of Chinese Medi-cine from December 15,2022 to January 15,2023 were conducted.Patients who died or were lost to follow-up within 48 h of admis-sion were excluded.Patients were divided into survival and death groups based on their 28-day fatality status.Descriptive statistics were used to characterize the two groups and multivariate logistic regression models were employed to identify factors influencing 28-day fatality risk.The interaction between the severity of illness at admission and the use of hospital preparations was explored through cross-over analysis and hierarchical regression analysis.RESULTS Significant differences were observed between the survival and death groups in terms of severity of illness at admission,hospital preparations usage,steroid therapy,age,platelet count,lactate dehydro-genase levels,and urea(P<0.05.Crossover analysis and hierarchical logistic regression analysis revealed a significant antagonistic interaction between the severity of illness at admission and the use of hospital formulations both before adjustment(RERI=-20.678,95%CI:-33.703～-7.652;APAI=-2.301,95%CI:-4.027～-0.575 and after adjusting for gender,age,clinical characteristics and further adjusting for laboratory parameters(RERI=-5.972,95%CI:-10.564～-1.380;APAI=-2.205,95%CI:-4.131～-0.279,and it was an antagonistic interaction both before(SI=0.279,95%CI:0.157～0.493 and after adjustment(SI=0.222,95%CI:0.095～0.523.CONCLUSION The use of hospital preparations significantly reduces the 28-day fatality risk among COV-ID-19 hospitalizations and a clear antagonistic interaction was observed between the disease severity at admission and the use of hospi-tal preparations.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

Objective To explore the early clinical characteristics and influencing factors in children with autism spectrum disorders(ASD).Methods From January 2005 to December 2014,193 children with ASD were collec-ted by continuous grouping method from Children's Rehabilitation Training Center in Xi'an.According to the 1∶1 matched case-control study requirements,and the other 193 children from kindergartens and primary schools in the urban areas of Xi'an were collected as healthy control group from March 1 to July 1,2016.The age of children in the case group was(40.78±14.86)months and the age of the healthy control group was(40.61±14.40)months.There were 167 boys and 26 girls in 2 groups and the ratio of boys to girls was 6.42∶1.00.The general status questionnaires,medical history questionnaire,diagnostic chart,Autism Behavior Checklist(ABC)and Family Environment Scale of Chinese version(FES-CV)were completed by parents between 2 groups.Childhood Autism Rating Scale(CARS)was completed by doctors in the case group.By using Excel software,the original questionnaires were completed in 2 entries by 2 persons to set up the database.All data were analyzed by SPSS 17.0 statistical software and conditional Logistic regression was used for multivariate analysis.Results Seventy point eight percent(137/193 cases)of children with ASD had been found abnormal under 2 years old or at 2 years old,and 54.9％(106/193 cases)had been diagnosed under 3 years old or at 3 years old.The average delay from the discovery to the diagnosis was 17 months.The initial abnormalities appea-rances were mainly manifested as no response to calling in 153 cases(79.3％),very little active contact with others in 141 cases(73.1％),silent or less use of oral language in 137 cases(71％),avoiding contact with the eyes of others or lack of facial expressions in 121 cases(62.7％).Their signs were easy to be misdiagnosed as mental retardation and language retardation.Children in the case group began to walk alone at the age of 8 months to 3 years old,and only 62.2％(120/193 cases)of them could walk alone at the age of 18 months or before.The age of conscious speech was at 8 months to 4 years and 4 months,and only 39.4％(76/193 cases)of the ASD children could speak at the age of 18 months or before.The total scores of the ABC scale of the case group were(56.520±22.140)scores and the sub-scales and total scores were significantly higher than those of the healthy control group,and the difference was statistically significant(t=16.845,27.390,16.527,26.320,23.371,32.206,all P<0.001).The positive consistent rate of ABC and clinical diagnosis was 56.5％.The total scores of CARS in the case group was(36.4±8.6)scores,and the positive consistent rate of CARS and clinical diagnosis was 78.8％.There was a statistical significance between the 2 groups in parental education,mother's occupation,family history(x2=29.670,44.593,15.439,6.095,all P<0.05),and there were statistical significance in the main caregivers,family harmony and family income(x2=19.006,7.129,109.027,all P<0.05).There was no statistical significance between the 2 dimensions of independence and achievement orientation between the 2 groups(t=-1.559,-0.139,P=0.120,0.890).The case group in the family cohesion,expressiveness,intellectual-cultural orientation,active-recreational orientation,moral-religious emphasis,organization and control of the 7 dimension scores were significantly lower than those in the healthy control group,and the differences were statistically significant(t=-7.683,-5.734,-8.762,-14.109,-2.026,-4.530,-2.464,all P<0.05).In the case group,the scores of the conflict dimension were higher than those of the healthy control group,and the difference was statistically significant(t=4.925,P<0.001).There was a statistical significance between the 2 groups in gestational age and birth hypoxia(x2=6.898,27.180,all P<0.05).According to multivariate analysis of Logistic regression,people other than parents serving as the primary support,anoxia of newborn,mother of non professional and technical personnel and lower scores of family active-recreational orientation might be the risk factors of ASD,family per capita income of 3 000 Yuan RMB or more monthly,mother education level of high school and above,and lower scores of family conflict might be the protective factors for ASD.Conclusions Clinical features of most ASD children can be easily identified under 2 years old,but if the diagnosis is delayed,the related intervention is late,so importance should be attached to early diagnosis.Mother's occupation and education level,family economic status,family environment,their supervisors,and anoxia of newborn may be the effective entry points in the prevention and treatment of ASD.

Objective To investigate the effects of Pinella's ingredients on the viability of cells, morphology, microstructure, cell cycle and apoptosis in human cervical cancer cell lines. Methods The β-sitosterol and/or total protein of Pinella were incubated at different concentrations with cervical cancer cell line SiHa. The effects of β-sitosterol and/or total protein of Pinella on the viability of cells were tested by MTT assay. The effects of β-sitosterol on morphology, microstructure, cell cycle and apoptosis were studied by phase-contrast microscope, electron microscope and flowcytometry, respectively. Results β-sitosterol could obviously inhibit the viability of SiHa cells in a time-and dose-dependent manner. The total protein of Pinella had no effects on SiHa cells' viability. 20 μmol/L β-sitosterol induced the accumulation of SiHa cells in S phase in the cell cycle. And the percents of apoptosis and necrosis increased. The morphology and microstructure of SiHa cells changed significantly after treated with 20 μmol/L β-sitosterol. Conclusions The total protein of Pinella had little influence on the viability of cervical cancer cells SiHa. The viability of SiHa cells could be suppressed by β-sitosterol. β-sitosterol could induce the accumulation of cells in S phase and the percent of apoptosis and necrosis. The morphology and microstructure changed significantly after treated with β-sitosterol. Therefore, β-sitosterol might be a prospect safe and low toxicity anti-cervical cancer drug.