ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People's Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study. Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality. Further stratification was performed according to preoperative deviation angles [>35 prism diopters(PD)vs ≤35 PD] and age(≥18 years adult group vs <18 years adolescent group). The baseline patient characteristics were collected, deviation angles at multiple timepoints before and after treatment were measured, and stereopsis test results were documented. Through comparative analysis of therapeutic outcomes across subgroups, we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included. At the final follow-up, both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001). Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05). For patients with deviations >35 PD, surgery yielded significantly better outcomes than injection therapy in postoperative angle, success rate, and stereopsis recovery(P<0.05). Similarly, in patients aged ≥18 years, surgical treatment was superior to injections in reducing strabismus angle, improving success rates, and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE. Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy, particularly in patients with deviations >35 PD and those aged ≥18 years. For patients with angles ≤35 PD or under 18 years, BTXA injection remains a viable treatment option.

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

ObjectiveTo observe the effects of Baihe Yuzi prescription （BYP） on the cystic fibrosis transmembrane conductance regulator （CFTR）， aquaporin （AQP）， zinc/iron-regulated transporter-like protein （ZIP） and local oxidative stress in epididymis of oligoasthenozoospermia （OAS） rats， and to explore the mechanism of its intervention in OAS. MethodAfter 35 rats were acclimatized for 1 week， 7 rats were randomly selected as the normal group， and the remaining 28 rats were given tripterygium glycosides （TG） 30 mg·kg^-1. After 4 weeks of modeling， they were randomly divided into 4 groups： model group， BYP low-dose group （LBYP）， BYP high-dose group （HBYP） and levocarnitine group， with 7 rats in each group. The rats in the normal group and model group were given normal saline at the same dosage. The levocarnitine group rats were given L-carnitine oral liquid （100 mg·kg^-1） by gavage. The LBYP group rats were given BYP 6.3 g·kg^-1， and the HBYP group rats were given BYP 12.6 g·kg^-1 by gavage once a day for consecutive 4 weeks. After the end of the intervention， sperm count and motility of all rats were detected， the histopathological structure of epididymis was observed by hematoxylin-eosin （HE） staining， and the expressions of CFTR， AQP9， AQP3， ZIP8， ZIP12 and other proteins were detected by Western blot. The contents of α-glycosidase （α-GC）， sialic acid （SA）， carnitine， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Total zinc content was measured using an inductively coupled plasma mass spectrometer. Free zinc ion content was detected by zinc ion probes. ResultCompared with those in the normal group， the sperm count and motility of rats were decreased and the epididymal structure was disordered in the model group. The contents of α-GC and carnitine were decreased in epididymis （P<0.05）. MDA levels were increased， while SOD， GSH-Px and zinc levels were decreased （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were down-regulated， and AQP3 expression was up-regulated. The expression of ZIP8 in the cauda epididymis was up-regulated （P<0.05）. Compared with the model group， BYP can significantly improve the sperm count and motility， the epididymal structure of OAS rats and the levels of α-GC and carnitine （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were up-regulated， while the expressions of ZIP8 in the cauda epididymis and AQP3 in the head of the epididymis were decreased （P<0.05）. The SOD and GSH-Px levels and total zinc content in epididymis were increased， and the MDA levels were decreased （P<0.05）. ConclusionBYP may improve the sperm quality and repair epididymal tissue structure and function of OAS rats， by regulating the expressions of CFTR， AQP3， and ZIP12 ion channels and local antioxidant mechanism.

Objective To study the relationship between serum neuron-specific enolase(NSE)and clinical features of pheochromocytoma/paraganglioma(PPGL).Methods Totally 501 PPGL patients diagnosed from January 2019 to December 2022 were divided into normal NSE group(NSE≤16.3 ng/mL)and elevated NSE group(NSE＞16.3 ng/mL).The clinical characteristics were compared between the two groups.Results Compared with normal NSE group,patients in the elevated NSE group had larger diameter in primary tumor(5.00 cm vs.4.60 cm),higher 24-hour urinary norepinephrine(NE)and 24-hour urinary dopamine(DA)levels,and a higher rate of metasta-sis(31.6%vs.13.7%)(P＜0.05).NSE level was positively correlated with the primary tumor size(r=0.131,P＜0.05),24-hour urinary NE level(r=0.195,P＜0.05)and 24-hour urinary DA level(r=0.119,P＜0.05).Conclusions The level of NSE is related to tumor size,secretion function and metastasis in PPGL patients.

AIM: To evaluate the safety and efficacy of ultrasonic cycloplasty(UCP)combined with anti-vascular endothelial growth factor(VEGF)+ panretinal photocoagulation(PRP)in the treatment of advanced neovascular glaucoma(NVG).METHODS: Retrospective study. A total of 45 patients(45 eyes)with advanced NVG who received surgery in our hospital from August 2020 to September 2022 were collected and divided into UCP+ anti-VEGF +PRP group(16 patients, 16 eyes), transscleral cyclophotocoagulation(TCP)+anti-VEGF+PRP group(20 patients, 20 eyes), UCP alone group(9 patients, 9 eyes). The intraocular pressure, pain scores, postoperative medication, effective rate, total success rate and the incidence of complications of the patients in the three groups were compared before surgery and at 1 d, 1 wk, 1 and 3 mo after surgery.RESULTS: There was no significant difference in preoperative intraocular pressure, pain scores and preoperative medication of patients in the three groups(all P>0.05). While there were statistical significance in the intraocular pressure and pain scores at 1 d, 1 wk, 1 and 3 mo after surgery(all P<0.01). The intraocular pressure of the UCP alone group(31.78±10.23 mmHg)was found to be higher than that of both the UCP+ anti-VEGF +PRP group(19.44±8.23 mmHg)and the TCP+ anti-VEGF +PRP group(20.80±10.27 mmHg)at 1 mo postoperatively(all P<0.017). The pain score of the TCP+ anti-VEGF +PRP group at 1 d and 1 wk postoperatively was higher than both the UCP+ anti-VEGF +PRP group and the UCP alone group(all P<0.017). The effective rates of UCP+ anti-VEGF +PRP group, TCP+ anti-VEGF +PRP group and UCP alone group were 81%(13/16), 75%(15/20)and 67%(6/9), respectively,(P=0.675), and the success rates were 69%(11/16), 50%(10/20), and 0(0/9), respectively(P=0.003). There was no significant difference in complications of patients in the three groups(P>0.05).CONCLUSION: UCP combined with anti-VEGF +PRP and TCP combined with anti-VEGF +PRP showed comparable efficacy in reducing intraocular pressure in advanced NVG. UCP combined with anti-VEGF+PRP was more effective in relieving pain and with no serious complications in advanced NVG. UCP alone can effectively control intraocular pressure and alleviate the pain of patients in the early postoperative period, but long-term control still requires anti-VEGF+PRP.

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Objective:To assess the goal fulfillment in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three in patients with diabetes who received intensified treatment at Peking Union Medical College Hospital and regular follow-up for 12 months, analyze the influencing factors, and explore the comprehensive management model for intensive diabetes treatment outpatient services.Methods:This study was a prospective, observational cohort study. The diabetes patients who received long-term regular follow-up at the intensive diabetes treatment outpatient clinic of Peking Union Medical College Hospital from 2012 to 2023 were selected as the research subjects. They were followed up and clinical data were collected at the 1st, 3rd, 6th, 9th, and 12th months of follow-up. The study assessed the goal fulfillment rates in terms of blood glucose, blood pressure, blood lipid, and the composite indicator of these three, with the goals of glycated hemoglobin (HbA1c)<7%, blood pressure<130/80 mmHg, and low-density lipoprotein cholesterol (LDL-C)<2.6 mmol/L. The study also analyzed the impact of factors, including gender, age, type of diabetes, duration of diabetes, body mass index, comorbidities, complications, and treatment regimens, on the outcomes of comprehensive diabetes management.Results:A total of 232 patients were included in the study, of whom 210 were with type 2 diabetes (90.5%), 13 with type 1 diabetes (5.6%), 5 with latent autoimmune diabetes of the adult (2.2%), 3 with diabetes after total pancreatectomy (1.3%), and 1 with mitochondrial diabetes (0.4%). After 3 months of intensified management, the goal fulfillment rates of blood glucose (67.7% vs. 34.1%, Kappa=0.336, P<0.001), blood pressure (53.4% vs. 37.5%, Kappa=0.159, P=0.001), blood lipid (59.1% vs. 39.2%, Kappa=0.198, P<0.001), and the composite indicator (20.7% vs. 3.0%, Kappa=0.177, P<0.001) were significantly increased. Continued treatment at 6, 9, and 12 months showed stable and sustained increases in the goal fulfillment rates of blood glucose, blood pressure, blood lipid, and the composite indicator. Logistic regression analysis showed that baseline hyperglycemia ( P=0.002), disease duration ≥5 years ( P<0.001), smoking ( P=0.009), alcohol consumption ( P=0.038), presence of diabetic complications ( P=0.001), combination therapy with oral antidiabetic drugs and insulin ( P<0.001), and use of antiplatelet drugs ( P=0.037) were risk factors for uncontrolled HbA1c. Baseline hypertension ( P<0.001), alcohol consumption ( P=0.030), and comorbid dyslipidemia ( P=0.028) were risk factors for uncontrolled blood pressure. Baseline uncontrolled LDL-C ( P=0.020) and non-use of statins ( P<0.001) were risk factors for uncontrolled blood lipid. Conclusions:Among patients with the long-term follow-up at our intensive diabetes treatment clinic, the goal fulfillment rates of blood glucose, blood lipid, blood pressure, and the composite indicator of these three are relatively higher. However, it is still necessary to improve patient compliance as much as possible, emphasize weight management, and persist on the comprehensive diabetes treatment.

Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

Objective To observe the effect of Shoutai Pills on endometrial decidualization of mice with recurrent spontaneous abortion(RSA);To explore its possible mechanism in the treatment of RSA based on histone modification.Methods Totally 40 female CBA/J mice were divided into normal group,model group,Shoutai Pills low-dosage group(7.5 g/kg),Shoutai Pills high-dosage group(15 g/kg)and dydrogesterone group(3 mg/kg).The normal group were co housed with BALB/C male mice,while the other groups were co housed with DBA/2 male mice to establish an RSA mouse model.After modeling,the administration groups were given corresponding medication solution by gavage,while the normal group and model group were given equal volume of pure water by gavage for 10 consecutive days.The embryo condition was observed and the embryo loss rate was calculated,ELISA was used to detect serum prolactin(PRL)content,HE staining was used to observe the morphological changes of decidual tissue,RT-PCR was used to detect PRL mRNA expression in decidual tissue,Western blot was used to detect the protein expressions of H4ac,H3K27ac,H3K27me3.Results Compared with the normal group,the model group mice showed a significant increase in embryo loss rate,a significant decrease in serum PRL content,disordered arrangement of decidual cells,and extensive bleeding and necrosis;the expression of PRL mRNA and protein in decidual tissue significantly decreased,the protein expressions of H4ac and H3K27ac significantly decreased,while the expression of H3K27me3 protein significantly increased,with statistical significance(P<0.05).Compared with the model group,the embryo loss rate of Shoutai Pills low-and high-dosage groups and the dexamethasone group significantly decreased,the serum PRL content significantly increased,tightly arranged decidual cells,reduced necrosis,and intact glands;the expression of PRL mRNA and protein in decidual tissue of mice in Shoutai Pills high-dosage group and the dexamethasone group significantly increased,the protein expressions of H4ac and H3K27ac significantly increased,the expression of H3K27me3 protein significantly decreased,with statistical significance(P<0.05).Conclusion Shoutai Pills can promote endometrial decidualization in RSA mice,which is related to the changes of histone modification in endometrial stromal cells.