ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.

OBJECTIVE To study the pharmacokinetic characteristics of ciprofol in pregnant and fetal rats， and provide reference for the application of ciprofol in cesarean section. METHODS Eight pregnant rats were selected. A single dose of 2.4 mg/kg of ciprofol was administered via the tail vein. One fetal rat was selected at 2， 4， 8， 12， 16， 25， 35， 45， 60， and 90 minutes respectively after ciprofol administration. Subsequently， whole blood samples were collected simultaneously from both the pregnant rats and fetal rats. HPLC-MS/MS method was used to determine the concentration of ciprofol in the bodies of pregnant and fetal rats. The ratios of fetal-to-maternal blood concentrations （F/M ratios） at each time point were calculated， and the F/M-time curves were plotted. Subsequently， non-compartmental pharmacokinetic parameters were computed using DAS 2.0 software. RESULTS Compared with pregnant rats， cmax， AUC0-90 min and AUC0-∞ of ciprofol in fetal rats were decreased significantly， while MRT was increased significantly （P＜0.05）. The F/M curve of ciprofol initially increased and then decreased， and between 0.16- 0.84， reaching a maximum value of 0.84 at 45 minutes. CONCLUSIONS Ciprofol can penetrate the placental barrier， and there are significant differences in pharmacokinetic parameters between pregnant and fetal rats. Moreover， the exposure level of ciprofol in fetal rats is much lower than that in pregnant rats. Therefore， ciprofol shows promise as an ideal anesthetic agent for cesarean section delivery.

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl₄-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl₄ olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl₄ induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.

Objective To compare the pharmacokinetic profiles of the two teriflunomide tablets in healthy Chinese subjects under fasting and fed conditions and to evaluate their bioequivalence and safety.Methods A randomized,open,single-dose,parallel trial design was used to enroll 31 and 32 healthy Chinese male subjects in the fasting and fed groups,who were randomized to a single oral dose of 14 mg of either reference or test preparation of teriflunomide tablets.The plasma concentrations of teriflunomide were determined using liquid chromatography-tandem mass spectrometry method,and Phoenix WinNonlin 8.1 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of teriflunomide.The main pharmacokinetic parameters of teriflunomide in the fasting group were as follows:Cmax were(2.14±0.27)and(2.27±0.33)μg·mL-1,AUC0-72h were(105.70±11.20)and(107.72±11.77)μg·mL-1·h,tmax was 1.49 and 0.99 h;the main pharmacokinetic parameters of teriflunomide in the fed group were as follows:Cmaxwere(1.83±0.17)and(1.75±0.22)μg·mL-1,AUC0-72h were(102.66±9.18)and(101.57±13.01)μg·mL-1·h,tmax was 4.01 and 4.99 h.The 90％confidence intervals for the geometric means of Cmax and AUC0-72h for reference and test preparations in the fasting and fed groups were in the range of 80％to 125％.Conclusion The pharmacokinetic characteristics of the 2 formulations were similar under fasting and fed administration conditions,with good bioequivalence and safety;Postprandial administration may delay the time to peak of the drug.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).
Pregnancy ; Humans ; Female ; Fertilization in Vitro/methods* ; Single-Blind Method ; Embryo Transfer ; Pregnancy Rate ; Acupuncture Therapy ; Endometrium/blood supply*

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

By exploring the core ideas of the "Xingnao Kaiqiao" theory, analyzing the relationship between the "Xingnao Kaiqiao" theory and the TCM encephalopathy, and exploring the necessity of acupuncture for the treatment of TCM encephalopathy, in order to clarify how to diagnose and treat brain diseases in acupuncture and moxibustion. The "Xingnao Kaiqiao" is the core of the theory of the "Tiaoshen", the acupuncture of "Xingnao Kaiqiao" was based on the principle of "Xingnao","Xingshen" and "Tiaoshen", the idea of the "Tiaoshen" was inseparable from the diagnosis and treatment of the TCM encephalopathy. Based on the special features of acupuncture therapy and complexity and particularity of TCM encephalopathy, acupuncture and moxibustion treatment of encephalopathy was supposed to have their own unique system of syndrome differentiation and treatment. During the practice of acupuncture, the diagnosis and treatment of TCM encephalopathy should be based on "brain", "Xingnao Tiaoshen" as a general rule, adding and subtracting from the main points of the "Xingnao Kaiqiao", and the different brain diseases are matched with appropriate treatments.

ObjectiveTo investigate the trends in diabetes mortality rate and the characteristics of decreased population in Fengxian District, Shanghai from 2012 to 2021. MethodsData from the death registration records of the residents in Fengxian District between 2012 and 2021, sourced from the Shanghai Death Surveillance System, were analyzed. Indicators such as the crude mortality rate due to diabetes, the standardized mortality rate, years of life lost (YLL), and the probability of premature death were estimated. Annual percentage change (APC) was used to analyze the temporal trends of mortality and the probability of premature death due to diabetes. Rate decomposition analysis was used to assess the contributions of demographic and non-demographic factors to diabetes mortality. ResultsFrom 2012 to 2021, there were 1 471 deaths due to diabetes in Fengxian District, with a crude mortality rate of 27.51/100 000 and a standardized mortality rate of 17.58/100 000. The crude mortality rate showed an overall increasing trend (APC=4.58%, Z=3.49, P<0.05). The potential years of life lost (PYLL) due to diabetes over this period amounted to 9 715 person-years, with a PYLL rate of 1.82 ‰, and the average years of life lost (AYLL) was 11.94 years. The probability of premature death was 0.41% (APC=3.36%, t=2.33, P<0.05). Both population aging and non-aging factors contributed to the increase in diabetes mortality, with overall contribution rates of 67.99% and 32.01%, respectively. Among men, the contribution rates were 60.57% and 39.43%, while among women, they were 79.43% and 20.57%, respectively. ConclusionFrom 2012 to 2021, both the crude mortality rate and the probability of premature death due to diabetes showed an upward trend among the residents in Fengxian District, with a higher YLL. Population aging was the main factor causing the increase in mortality rate, while non-demographic factors had a greater impact on the rise in diabetes mortality among men than that in women. Therefore, the management on male diabetes patients should be strengthened.

To explore the application value of SAA (serum amyloid A), CRP (C reactive protein), PCT (procalcitonin), WBC (white blood cell) and N% (neutrophil %) in the diagnosis of neonatal septicemia. This study was a retrospective study. 173 children with clinically diagnosed septicemia and 66 children with definitely diagnosed septicemia admitted to the Department of Neonatology, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China,from January 2022 to January 2024 were selected as the case group, and 148 children with neonatal jaundice who were hospitalized during the same period were selected as the control group. Fasting venous blood was collected within 24 hours after the children′s admission to detect the levels of serum WBC, N%, SAA, CRP and PCT. One-way analysis of variance and Kruskal-Wallis H test were used to compare the general data and inflammatory index levels of the three groups of children. The correlation analysis between SAA and other inflammatory indicators was conducted using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was used to determine the diagnostic efficacy of different inflammatory indicators for patients with definitely diagnosed septicemia and those with clinically diagnosed septicemia, and for those with clinically diagnosed septicemia and those without infection. The results showed that the levels of WBC [(16.88±5.64)×10 9/L], N% [70.00 (63.00, 75.00)], PCT [2.22 (1.20, 5.55) mg/L], CRP [3.00 (0.50, 10.30) mg/L], SAA [19.70 (10.82, 49.90) mg/L] in the clinically diagnosed septicemia group and WBC [(16.10±7.48)×10 9/L], N% [73.50 (61.50, 80.93)], PCT [5.35 (0.69, 20.07) mg/L], CRP [15.52 (4.98, 30.50) mg/L], SAA [43.95 (14.00, 175.98) mg/L] in the definitely diagnosed septicemia group were all higher than those in the control group (11.17±3.38)×10 9/L, 49.81 (36.93, 62.75), 0.20 (0.07, 0.99) mg/L, 0.54 (0.20, 1.40) mg/L, 5.15 (3.60, 8.68) mg/L, and the differences were all statistically significant (all P<0.05). Spearman correlation analysis showed that the level of SAA was positively correlated with WBC, N%, PCT and CRP ( rs=0.453, 0.540, 0.343, 0.550, all P<0.05). ROC curve analysis showed that the area under ROC curve(AUC) of SAA for the definitely diagnosed septicemia group and the clinically diagnosed septicemia group was higher than that of other inflammatory indicators, among them, the AUC of SAA for diagnosing the definitely diagnosed neonatal septicemia group was 0.933 (95% CI: 0.809-1.000, P<0.05), with a sensitivity of 92.90% and a specificity of 99.30%. The AUC of SAA for diagnosing the clinically diagnosed septicemia group was 0.861 (95% CI: 0.818-0.904, P<0.05), with a sensitivity of 83.20% and a specificity of 81.80%. In conclusion, compared with CRP, PCT, WBC and N%, SAA has higher sensitivity and specificity for distinguishing neonatal septicemia (including definitely diagnosed septicemia and clinically diagnosed septicemia), and has certain auxiliary diagnostic value for neonatal septicemia.