ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

Asymptomatic carotid artery stenosis (aCAS) is one of the important causes of ischemic stroke. The imaging evaluation of carotid artery plaques is of great significance for selecting the best treatment in patients with aCAS. This article reviews the plaque composition, plaque morphology, and hemodynamic evaluation of aCAS, aiming to provide a basis for developing personalized medical strategies.

Objective: As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. Methods: This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. Results: After a median follow-up of 137.0 months (95% confidence interval=85.4–188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). Conclusions The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

AIM:To investigate the molecular mechanism underlying ferroptosis induced by celastrol(Cel)in huamn pancreatic cancer cell line PANC-1.METHODS:The viability of PANC-1 cells was analyzed by MTT assay,and the effects of Cel on cell proliferation were analyzed using EdU and colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess and observe changes in lipid reactive oxygen species(ROS)levels,respectively,while the levels of malondialdehyde(MDA),glutathione(GSH)and Fe2+were measured using specific kits.The protein expression of glutathione peroxidase 4(GPX4)was evaluated by Western blot,and GPX4 ubiquitination was measured by immunoprecipitation.RESULTS:It was found that the viability,proliferation and colony formation in PANC-1 cells de-creased gradually as the concentration of Cel increased.Addition of Cel alone to the cells reduced both cell rounding and viability,while treatment with ferrostatin-1(Fer-1)alone or in combination with Cel had no effect on either cell morpholo-gy or viability.Fluorescence staining of lipid ROS with BODIPYTM 581/591 C11 followed by flow cytometry analysis showed significantly increased levels of green fluorescence indicative of oxidized lipid ROS,which were further increased after treatment of the cells with Cel.Treatment of the cells with both Cel and Fer-1 reduced the green fluorescence and lip-id ROS levels.Treatment with Cel also increased the levels of MDA and Fe2+,relative to the controls,which reducing the levels of GSH,while addition of both Cel and Fer-1 to the cells restored the levels of MDA,Fe2+,and GSH to those of the control group.CONCLUSION:Treatment with Cel reduces the proliferation of pancreatic cancer cells by inducing fer-roptosis through promoting the ubiquitination and degradation of GPX4.

The integration of ideological and political education into medical courses is an important part of China's medical education reform in the new era.The construction of ideological and political education in clinical research curriculum is of great significance for the cultivation of clinical research talents with both ability and political integrity.Based on the clinical research curriculum offered by the Second Clinical College of Wuhan University,this paper introduced the necessity of ideological and political curriculum in clinical research curriculum.Through the learning situation analysis of the eight-year program students majoring in clinical medicine,the ideological and political teaching objectives were formulated,and the ideological and political elements and cases were selected in combination with the teaching content of clinical research curriculum.Combined with the characteristics of the medical professional methodology course,the diversified,innovative student-centered teaching methods were designed integrating the theoretical teaching,flipped classroom,scenario simulation teaching,problem-based learning,case-based learning and team based learning,and added the consideration of moral education dimension in the teaching evaluation,to carry out the ideological and political teaching design of clinical research curriculum.These measures promoted the organic integration of knowledge teaching,ability training and value building,and provided reference for the ideological and political education in clinical research curriculum.

Objective:To explore the changes of iron metabolism in patients with hepatitis B cirrhosis and esophageal and gastric varices complicated with portal vein thrombosis.Methods:This study was a cross-sectional study. 253 patients with hepatitis B cirrhosis with esophageal and gastric varices who were hospitalized in the Zhongshan Hospital, Fudan University from January 1, 2020 to December 31, 2021 were included in this study. They were divided into portal vein thrombosis group ( n=57) and non portal vein thrombosis group ( n=196) according to the presence or absence of portal vein thrombosis. The iron metabolism characteristics of the two groups were compared, and subgroups were analyzed according to the presence or absence of ascites, platelet count level, D-dimer level, and Child grade. The factors related to portal vein thrombosis were screened through multivariate logistic regression analysis. Results:The ratio of Child pugh B/C, ascites, D-dimer and platelet count in patients with hepatitis B cirrhosis and esophageal and gastric varices complicated with portal vein thrombosis was higher (all P<0.05). Patients with portal vein thrombosis had higher levels of soluble transferrin receptor [2.4(1.8, 3.6)mg/L vs 1.8(1.3, 2.7)mg/L, P=0.006], and lower levels of ferritin [33.1(18.9, 63.3)ng/ml vs 57.7(19.4, 142.5)ng/ml, P=0.038]. Layered analysis showed that ascites, platelet count levels, D-dimer levels, and Child-pugh grade did not affect the negative correlation trend between ferritin and portal vein thrombosis, and the positive correlation trend between soluble transferrin receptors and portal vein thrombosis. Moreover, soluble transferrin receptors showed a statistically significant positive correlation with portal vein thrombosis in the absence of ascites, low D-dimer levels, and Child-pugh grade A. Multivariate analysis suggested that after weighing Child-pugh grading, platelet count, and D-dimer levels, ferritin ( OR=0.943, 95% CI: 0.904-0.983, P=0.006) and soluble transferrin receptor ( OR=1.034, 95% CI: 0.001-1.067, P=0.044) were independently associated with portal vein thrombosis. Conclusions:In patients with hepatitis B cirrhosis with esophageal and gastric varices, the characteristics of iron metabolism in patients with portal vein thrombosis are different from those in patients without thrombosis, with higher levels of soluble transferrin receptor and lower levels of ferritin.

Objective:To investigate whether discontinuation of previous targeted immunotherapy increases the risk of rebleeding in patients with advanced liver cancer complicated with esophageal and gastric variceal bleeding after endoscopic treatment.Methods:A retrospective cohort study was conducted to include advanced liver cancer patients who were diagnosed with esophageal and gastric variceal bleeding through endoscopic examination and treated under endoscopy at Zhongshan Hospital, Fudan University from March 1, 2020 to March 1, 2022, due to upper gastrointestinal bleeding. We collected clinical data from patients and divided them into targeted immunotherapy group and non targeted immunotherapy group based on whether they received targeted immunotherapy before bleeding; Follow up observation was conducted for 6 months to evaluate the patient′s re bleeding and survival status.Results:A total of 55 patients were included, of which 24 had previously received targeted immunotherapy and 31 had not received targeted immunotherapy. There was no significant difference between the two groups in gender distribution, etiology, hypertension and diabetes (all P>0.05). The age of the target immunotherapy group was younger than that of the non target immunotherapy group, and the level of fibrinogen was higher than that of the non target immunotherapy group, with statistical significance ( P=0.002, 0.017). There was no statistically significant difference in the 6-month re bleeding rate (20.83% vs 22.58%, P=0.269) and 6-month mortality rate (45.83% vs 29.03%, P=0.199) between the targeted and non targeted groups of patients. Further Cox regression multivariate analysis revealed that Child-pugh grading was an independent risk factor for 6-month survival in patients with advanced liver cancer with esophageal and gastric varices ( HR=2.64, P=0.009). Conclusions:Targeted immunotherapy does not increase the rate of rebleeding in patients with advanced unresectable liver cancer after endoscopic treatment of esophageal and gastric varices. Child-pugh grading is a factor that affects the 6-month survival of advanced liver cancer patients after bleeding, and the poorer the liver function, the shorter the survival period.

The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.

Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.