ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction （半夏泻心汤， BXD） in the treatment of diabetic gastroparesis （DGP）. MethodsA total of 29 SD rats were randomly divided into four groups， blank group （5 rats） and model group， BXD group and metformin group （8 rats in each group）. Except for the blank group， rats were administered intraperitoneally with 1% streptozotocin （STZ） solution and were fed a high-sugar， high-fat diet to establish the DGP rat model. After successful modeling， the BXD group was treated with BXD at 6.68 g/（kg·d） by gavage， the metformin group was treated with metformin hydrochloride at 105 mg/（kg·d） by gavage， and the blank group and the model group were treated with normal saline at 6.68 ml/（kg·d） by gavage， for 8 weeks. After the last administration， fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， total cholesterol （TC）， triglycerides （TG） were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin （MTL） and gastrin （GAS）， as well as inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β） and interleukin-10 （IL-10） in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin （HE） staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α （LXRα） levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue， and of janus kinase 2 （JAK2）， phospho-janus kinase 2 （p-JAK2）， signal transducer and activator of transcription 3 （STAT3） and phospho-signal transducer and activator of transcription 3 （p-STAT3） in gastric antrum tissue. Quantitative real-time polymerase chain reaction （qPCR） was used to measure the mRNA expression of LXRα in liver tissue and JAK2， STAT3 in gastric antrum tissue. ResultsCompared with the blank group， the model group showed significant hepatic fatty degeneration， gastric antrum tissue structure destruction， and increases in FBG， HbA1c， TC， and TG levels； the average fluorescence intensity， protein level， and mRNA expression of LXRα in liver tissue were reduced； the gastric emptying rate and gastric tissue GAS and MTL levels decreased； inflammatory factors including TNF-α， IL-6， IL-1β in gastric tissue increased， IL-10 decreased； in gastric antrum tissue， the mRNA expression of p-JAK2/JAK2， p-STAT3/STAT3， and JAK2 and STAT3 increased （P＜0.01）. Compared with the model group， both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology； FBG， HbA1c， TC， and TG levels decreased， while LXRα fluorescence intensity， protein level， and mRNA expression in liver tissue significantly increased； the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher； the levels of TNF-α， IL-6， and IL-1β decreased， whereas IL-10 levels increased， p-JAK2/JAK2， p-STAT3/STAT3， and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased （P＜0.05 or P＜0.01）. The BXD group showed higher level than the metformin group in FBG， HbA1c， and TG levels， lower level in gastric emptying rate and gastric tissue GAS content， and higher level in gastric tissue TNF-α， IL-6， IL-1β levels； there was also a decrease in IL-10 levels， and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue， as well as in p-JAK2/JAK2 levels in gastric antrum tissue （P＜0.05 or P＜0.01）. ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.

Diabetes mellitus （DM） is a metabolic disease caused by absolute or relative insulin deficiency and reduced insulin sensitivity in peripheral cells， posing a serious threat to global health. Chronic complications arising in the later stages of DM can lead to the decline or even loss of function in multiple organs， including the eyes， heart， liver， kidneys， nerves， and feet， making them the primary cause of mortality in DM patients. Although modern medicine has made some progress in the treatment of these complications， challenges such as high costs and adverse drug reactions remain. Thus， identifying highly effective drugs with minimal adverse effects has become a top priority. Astragalus membranaceus is a shining gem in the treasure trove of Chinese medicine. Numerous studies have shown that its primary active component， astragaloside Ⅳ， possesses various biological activities， including anti-inflammatory， antioxidant， and antiviral effects， as well as benefits for cardiac and cerebral function， nerve conduction， and myocardial protection. Meanwhile， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a crucial role in regulating oxidative stress， inflammatory responses， apoptosis， and autophagy. Extensive research has highlighted the significant role of this pathway in various DM complications， leading to widespread studies on its interaction with astragaloside Ⅳ. This review summarizes research findings on how astragaloside Ⅳ alleviates pancreatic cytotoxicity in DM patients by modulating the PI3K/Akt pathway. Additionally， it highlights its protective effects on basic cardiac function， inhibition of retinal cell damage， improvement of cerebral nerve dysfunction， reduction of chronic kidney and liver damage， and mitigation of neurovascular toxicity in the lower limbs. These insights provide a valuable reference for the clinical application of A. membranaceus and its active monomer， astragaloside Ⅳ， in the treatment of DM and its complications.

To investigate the pharmacological activities and potential mechanisms of action of the active components in Artemisia argyi with artificial intelligence technology, a search was conducted in the HIT, TCMSP, and TCMIO databases, obtaining 199 active components of A. argyi. A comprehensive set of algorithms, including KNN, MLP, RF, SVM, and models based on Lipinski’s and Veber’s rules, was employed to predict the toxicity and oral bioavailability of A. argyi compounds, identifying 14 components that are non-toxic and have good oral bioavailability. The synthetic accessibility score (SAscore) model was used to analyze the synthetic accessibility of the 14 components mentioned above, and molecular segments were fragmented using BRICS and RECAP algorithms. Mining of the STP and PM databases yielded 406 target proteins for the core components of A. argyi, and Cytoscape was used to screen out 5 core targets: SRC, EGFR, PTPN11, HRAS, and PDGFRB. GO and KEGG enrichment analyses indicated that the core targets were involved in 808 GO enrichment analysis entries and 71 signaling pathways, including EGFR tyrosine kinase inhibitor resistance, gap junction, phospholipase D, and JAK/STAT. Molecular docking results showed that active compounds of A. argyi have a good binding affinity with proteins SRC, EGFR, PTPN11, and HRAS. Cellular experiments have confirmed that ledol, an active component of A. argyi, can promote the proliferation of HUVEC cells within a certain concentration range and can increase the expression of EGFR protein. This study reveals the pharmacological characteristics and potential molecular mechanisms of the active components of A. argyi and lays a solid scientific foundation for its medicinal development.

Objective To investigate the distribution and clinical characteristics of TCM syndromes in infertility patients with autoimmune thyroiditis(AIT).Methods By referring to the relevant literature on the distribution of TCM syndromes of AIT and infertility in women of childbearing age,the TCM Syndromes Survey of Infertility Patients with Autoimmune Thyroiditis was formulated.256 cases of infertility patients with AIT who underwent in vitro fertilization-embryo transfer(IVF-ET)at the Reproductive Center of The First Affiliated Hospital of University of Science and Technology of China from June 2019 to December 2020 were retrospectively analyzed.The data of basic information,TCM syndromes,basic thyroid-stimulating hormone(TSH),thyroid peroxidase antibody(TPO-Ab)and thyroglobulin antibody(TG-Ab)were collected.By means of frequency analysis and systematic cluster analysis,the distribution regularity of TCM syndromes in infertility patients with AIT were concluded.Results After analysis,the following 5 common syndrome elements were obtained,namely,qi deficiency,liver depression,spleen deficiency,kidney deficiency and blood stasis.In addition,it was concluded that this disease was more common in complex syndromes.Through systematic clustering analysis,main TCM syndromes of this disease were obtained,which were qi deficiency and liver depression syndrome(69 cases,26.9%),spleen and kidney deficiency syndrome(45 cases,17.6%),spleen qi deficiency syndrome(38 cases,14.8%),qi deficiency and blood stasis syndrome(36 cases,14.1%),kidney deficiency and liver depression syndrome(32 cases,12.5%)and other syndrome types(36 cases,14.1%).The basic TSH level was higher in patients with qi deficiency and liver depression syndrome,spleen qi deficiency syndrome,qi deficiency and blood stasis syndrome than other syndrome types,with statistical significance(P<0.05).There was no significant difference in TPO-Ab and TG-Ab titers among different syndromes(P>0.05).Conclusion TCM syndromes of infertility patients with AIT can be clustered into qi deficiency and liver depression syndrome,spleen and kidney deficiency syndrome,spleen qi deficiency syndrome,qi deficiency and blood stasis syndrome,kidney deficiency and liver depression syndrome and other syndrome.The main element of syndrome is qi deficiency,and the pathological sites involved spleen,kidney and liver.Stasis blood is a main pathological product.It is required to pay close attention to the thyroid function in AIT patients with qi deficiency.

Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.

Objective:To explore the regulatory effects of Danzhi Jiangtang Capsules on glucose metabolism and mitochondrial oxidative stress levels in db/db mice.Methods:Totally 32 db/db mice were randomly divided into model group, positive control group, and Danzhi Jiangtang Capsule low-, medium- and high-dosage groups; at the same time, 8 same-sex C57BL/6 mice of the same week age were selected as the blank group. The metformin group was filled with metformin solution 0.1 g/kg, and the Danzhi Jiangtang Capsule low-, medium- and high-dosage groups were injected with 0.99, 0.49 and 0.25 g/kg Danzhi Jiangtang Capsule solution respectively. The model group and the blank group received the same volume of physiological saline solution for the gavage, 1 time/d, continuous 12 weeks. The weight and fasting blood sugar (FBG) changes in each group of mice were detected; the serum insulin (FINS) level was detected by ELISA method and the insulin resistance index (HOMA-IR) was calculated; kits were used to detect the pancreatic tissue SOD and MDA levels of each group of mice; HE staining was used to observe pathological morphology of pancreatic tissue. Transmission electron microscopy was used to observe the ultrastructure of pancreatic mitochondria; Western blot method was used to detect the expressions of p-AMPK and AMPK proteins in pancreatic tissue.Results:Compared with the model group, after 8 or 12 weeks of drug administration, the weight of mice in the Danzhi Jiangtang Capsule high-dosage group decreased ( P<0.05 or P<0.01), and the level of FBG decreased ( P<0.01); FINS and HOMA-IR in the Danzhi Jiangtang Capsule high- and medium-dosage groups decreased ( P<0.01), the SOD activity in Danzhi Jiangtang Capsule high- medium- and low-dosage groups increased, and the level of MDA decreased ( P<0.01); the expressions of p-AMPK and AMPK in Danzhi Jiangtang Capsule high-and medium-dosage groups increased ( P<0.01), the expression of AMPK in Danzhi Jiangtang Capsule low-dosage group increased ( P<0.01). Conclusion:Danzhi Jiangtang Capsule can improve SOD activity in pancreatic tissue of db/db mice, reduce MDA content, and activate the AMPK signaling pathway, suggesting that Danzhi Jiangtang Capsule can improve insulin resistance and restore glucose homeostasis by inhibiting oxidative stress levels and improving mitochondrial function.

Waardenburg syndrome is a rare genetic disease of auditory pigmentation. The main symptom is sensorineural hearing loss. Pigment disorders and other developmental defects in skin, hair, iris, fundus and other parts are specifically divided into four different subtypes, each of which corresponds to different pathogenic genes, which encode transcription factors and signaling molecules that play a key role in the development process of neural crest cells into melanocytes. Because there are multiple subtypes of Waardenburg syndrome, different subtypes exhibit different symptoms, signs and ocular manifestations. Patients with Waardenburg syndrome are often first treated in ENT head and neck surgery due to hearing loss. Lack of theoretical knowledge related to Waardenburg syndrome by ophthalmologists may lead to misdiagnosis or missed diagnosis. Although there are currently limited treatments for the disease, with the continuous development of gene therapy and hearing management methods, the future treatment prospects will be broader.

Objective:To screen the differentially expressed genes(DEGs)under high phosphate-induced calcification in the vascular smooth muscle cells(VSMCs)by mRNA high-throughput sequencing technology,and to analyze the key genes and signaling pathways involved in the VSMCs calcification.Methods:The human VSMCs were divided into control group and model group.The cells in model group was exposed to the high-phosphate medium,while the cells in control group were cultured in DMEM supplemented with 10%fetal bovine serum under the same conditions.The VSMCs in two groups,stably transfected,were cultured for 12 d.The morphology of the cells in two groups were observed and photographed under inverted microscope.The DEGs were selected by Hisat2 software,and Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by Stringtie software from three aspects,such as biological processes(BP),molecular functions(MF),and cellular components(CC).The calcification of the cells in two groups was observed by Von Kossa staining method.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to analyze the expression levels of alkaline phosphatase(ALP),bone morphogenetic protein 2(BMP2),alpha-smooth muscle actin(α-SMA),tumor protein 53(Tp53),glutathione peroxidase 4(GPX4),ferritin light chain 1(Ftl1),and glycosylphosphatidylinositol-specific phospholipase D1(GPLD1)mRNA in the cells in two groups.Results:Compared with control group,there were 2 524 DEGs in the cells in model group,and there were 1 368 upregulated DEGs and 1 156 downregulated DEGs.Clustering of DEGs between the cells in two groups was distinct.The GO functional and KEGG pathway enrichment analysis results showed that the upregulated DEGs were primarily involved in regulating the microtubule cytoskeleton,cell polarity,protein localization,and cell cycle regulation among BPs;in constructing cell membrane,microtubule organization,chromosomes,and kinetochore among CCs;and functioning in phosphatidylinositol phosphate,Rho GTPase protein binding,transmembrane transport,and protein kinase regulatory activity among MFs.Downregulated DEGs were mainly involved in cytoplasmic translation,protein membrane localization,mRNA metabolism,and protein endoplasmic reticulum localization among BPs;in forming ribosome subunits,cell membrane,and autophagy among CCs;and functioning in single-stranded DNA,ribonucleoprotein complex,growth factor binding,regulating protein kinase activity,and catalytic activity among MFs.Seven signaling pathways were significantly enriched in upregulated genes,most notably in the biosynthesis of glycosylphosphatidylinositol(GPI)anchors;whereas 18 signaling pathways were significantly enriched in the downregulated genes,most notably in ferroptosis.The RT-qPCR results showed that compared with control group,the expression levels of GPX4,Ftl1,and Tp53 mRNA in the cells in model group were significantly decreased(P<0.01),while the expression level of GPLD1 mRNA was significantly increased(P<0.01);compared with control group,the expression level of α-SMA mRNA in the cells in model group was significantly decreased(P<0.01),and the expression levels of ALP and BMP2 mRNA were significantly increased(P<0.01).Conclusion:The VSMCs underwent calcification and normal cells exhibit the DEGs.The key signaling pathways in the calcification induced by high phosphate in the VSMCs include ferroptosis and GPI anchor biosynthesis,mediated primarily through GPX4,Ftl1,Tp53,and GPLD1.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective:To explore the influencing factors and effectiveness of community follow-up in patients with cardiac implantable electronic device (CIED) implantation.Method:A total of 132 patients who received CIED implantation in the Department of Cardiology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine from February 2021 to February 2022 were enrolled in this prospective cohort study. Among them 33 patients were followed up in community health service centers associated with Tongren Hospital (community follow-up group) and 99 matched patients were followed up in the CIED outpatient clinic of the hospital (outpatient follow-up group) with a ratio of 1∶3. The clinical data of the selected patients were collected through a questionnaire survey; the follow-up data were extracted through the CarelinkExpress electronic follow-up platform and the CIED outpatient information system of Tongren Hospital. Adjustment of the treatment protocol or CIED parameters at follow-up, and the referral from the community health service centers were defined as visit with-an-action (VWA). The endpoint of follow-up was the occurrence of major adverse events. The multivariate logistic regression model was used to analyze the factors influencing patient selection for community follow-up.Results:The univariate analysis showed that the frequency of visits to community health service centers and the service contracting rate in community follow-up group were higher than those of outpatient follow-up group ( P<0.05). The multivariate logistic regression analysis showed that the contracted community physician service was an independent influencing factor of patient choosing community follow-up ( OR=2.143, 95% CI: 1.103-4.166, P=0.025). A total of 469 visits of followed up occurred in 132 patients, including 45 community visits and 424 outpatient visits. VWA accounted for 22.2% (10/45) in the community follow-up group, and 17.2% (73/424) in the outpatient follow-up group ( P>0.05). There was no significant difference in the safety and effectiveness indicators (VWA, major adverse events, and unplanned follow-up) between the two groups ( P>0.05). More patients in the community follow-up group walked to the hospital than the outpatient follow-up group ( P<0.05);and the main transportation for the later was by bus or taxi(42(42.4%)or 41(41.4%)). The average waiting time in the community follow-up group was significantly shorter than that in outpatient follow-up group ( P<0.05). The total time required for a single follow-up in the community follow-up group was 50.0 (45.0, 59.5) minutes, which was significantly shorter than that in the routine outpatient follow-up group (107.0 (90.0, 135.0) minutes, P<0.05). Conclusions:The contracting with community physicians is an independent influencing factor for CIED implanted patients to choose community follow-up. The safety and effectiveness of community follow-up are comparable to routine outpatient follow-up, and community follow-up is more convenient.