Retinal microcirculatory disorder is a key factor in the occurrence and development of diabetic retinopathy （DR）， and also an important link in the prevention and treatment of DR. The theory of "Gaozhuo" holds that the microcirculatory disorder in DR is based on the deficiency of spleen Qi and is characterized by the obstruction caused by "Gaozhuo" and blood stasis. The deficiency of spleen Qi is an essential precondition for the endogenous formation and accumulation of Gaozhuo， while Gaozhuo invasion is the direct cause of microcirculatory disorders in DR. The deficiency of spleen Qi and the endogenous formation of Gaozhuo mean the process in which glucose metabolism dysfunction induces an excessive production of inflammatory factors and lipid metabolites. The obstruction caused by "Gaozhuo" and blood stasis is the direct pathogenesis of microcirculatory disorders in DR， encompassing two stages： Gaozhuo obstruction and turbidity and stasis stagnation. Gaozhuo obstruction and turbidity and stasis stagnation represent the process in which inflammatory factors and lipid metabolites damage the retinal microcirculation and induce thrombosis， thus mediating microcirculatory disorders. Turbidity and stasis stagnation and blood extravasation outside the vessels reveal the progression to microvascular rupture and hemorrhage resulting from the microcirculatory disorders. According to the pathogenesis evolution of the theory of "Gaozhuo"， microcirculatory disorders in DR can be divided into deficiency of spleen Qi with Gaozhuo obstruction， deficiency of spleen Qi with turbidity and stasis stagnation， and turbidity and stasis stagnation with blood extravasation outside the vessels. Clinically， treatment principles should focus on strengthening the spleen and benefiting Qi， resolving turbidity， and dispersing stasis. Different syndrome patterns should be addressed with tailored therapies， such as enhancing the spleen and benefiting Qi while regulating Qi and reducing turbidity， strengthening the spleen and benefiting Qi while resolving turbidity and dispelling stasis， and strengthening the spleen and resolving turbidity while removing stasis and stopping bleeding. Representative prescriptions include modified Wendantang， modified Buyang Huanwutang， modified Danggui Buxuetang， Zhuixue Mingmu decoction， Tangmuqing， Shengqing Jiangzhuo Tongluo Mingmu prescription， Danhong Huayu decoction， and Yiqi Yangyin Huoxue Lishui formula.

BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

BACKGROUND:Triptolide,a bioactive component of the traditional Chinese medicine Tripterygium wilfordii,has a certain protective effect on neurons.OBJECTIVE:To investigate the effect of triptolide on cerebral ischemia/reperfusion injury.METHODS:(1)Cell experiment:Hippocampal neurons(HT22 cells)were randomly divided into control group,glucose oxygen deprivation/reoxygenation(OGD/R)group,OGD/R+triptolide group,OGD/R+triptolide+si-TIGAR group,OGD/R+si-TIGAR group,and OGD/R+triptolide+rapamycin group.HT22 cell viability was detected by cell counting kit 8.Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,7 members of the solsolic vector family 11,sphingosine kinase 1(SPHK1)and(mTOR)were detected by western blot assay.Glutathione,malondialdehyde and iron level were detected using the biochemical kit.(2)Animal experiment:Rats were randomly divided into sham surgery group,model group,and triptolide group.Cerebral artery occlusion/reperfusion rat models were prepared in the latter two groups.Rats in the triptolide group were orally administered 50 mg/kg triptolide for 7 days.Twenty-four hours after administration,LONGA method was used to evaluate the neurological impairment of rats,TTC method was used to observe the conditions of cerebral infarction,TUNEL staining was used to detect cell apoptosis,and western blot was performed to detect the expression level of related proteins.RESULTS AND CONCLUSION:(1)At the cellular level,triptolide promoted cell viability and inhibited apoptosis in HT22 cells treated with OGD/R.Triptolide also increased the expression levels of Tp53-induced glycolysis and apoptosis factors,glutathione peroxidase 4,and 7 members of the solsolic vector family 11,activated the SPHK1/mTOR pathway,increased glutathione content,inhibited malondialdehyde content and iron levels.Rapamycin treatment counteracted the protective effect of triptolide on HT22 cells.(2)At the animal level,triptolide significantly reduced neurological deficits,infarct volume,and cell apoptosis,and inhibited neuronal ferroptosis in brain tissue of rats.To conclude,triptolide can inhibit ferroptosis by upregulating the expression level of Tp53-induced glycolysis and apoptosis factors and activating the SPHK1/mTOR signaling,and thereby reduced cerebral ischemia/reperfusion injury.These findings suggest that triptolide may be a candidate drug for the treatment of cerebral ischemia/reperfusion injury.

BACKGROUND/OBJECTIVES: Unhealthy diets are associated with chronic stress. An allostatic load (AL) is a comprehensive physiological index that measures the chronic stress response of the body. As a healthy dietary pattern, the role of Dietary Approaches to Stop Hypertension (DASH) in the development of an AL during pregnancy remains unclear. This study examined the relationship between the DASH dietary pattern and AL during pregnancy. SUBJECTS/METHODS: This study was a prospective study. From January 2024 to November 2024, 134 pregnant women in the second trimester (23–27 weeks) and third trimester (32–36 weeks) of pregnancy who met the inclusion and exclusion criteria in the obstetrics clinic of a tertiary general hospital in Anhui Province were selected for a questionnaire survey, physical examination, and laboratory examination. The DASH dietary pattern was assessed using the DASH scoring tool, and the total AL score was calculated using nine biomarkers that represent the cardiovascular, metabolic, and immune systems. Logistic regression was used to analyze the relationship between the DASH score and AL. RESULTS: One hundred and thirty-four pregnant women were included in this study. At the second and third trimesters, 41.8% and 37% of pregnant women, respectively, were in the high AL group. The binary logistic regression results showed that the DASH score was negatively correlated with the AL in the unadjusted model (odds ratio [OR], 0.878; 95% confidence interval [CI], 0.807–0.957; P = 0.003) and adjusted model (OR, 0.878; 95% CI, 0.792–0.973; P = 0.013) in the second trimester, the DASH score was negatively correlated with the AL in the unadjusted model (OR, 0.832; 95% CI, 0.758–0.913; P < 0.001) and adjusted model (OR, 0.806; 95% CI, 0.716–0.908; P < 0.001) in the third trimester. CONCLUSION The DASH score was negatively correlated with the AL in pregnant women.A low DASH score may increase the risk of a high AL, which may have adverse effects on physical and mental health.

ObjectiveTo address the shortage of high-caliber multidisciplinary professionals in China's rehabilitation engineering field and the prominent issue of "separation between medicine and engineering" in existing curricula, this study introduces the World Health Organization rehabilitation competency framework (RCF) to construct a systematic curriculum system for rehabilitation engineering. MethodsGuided by the four core competency domains of RCF (practice, professionalism, learning and development, management and leadership) and their associated supporting knowledge, the rehabilitation engineering curriculum was restructured into a modular framework, piloted and validated within the Biomedical Engineering (Intelligent Robotics) program at University of Health and Rehabilitation Sciences. ResultsA four-tiered curriculum system comprising General Education-Disciplinary Platform-Professional Core-Diverse Electives with a total of 160 credits was established, achieving precise mapping between competency objectives and course content. The students in the pilot cohort demonstrated outstanding academic performance (50% ranked in the top ten of their major), they also gained a deeper understanding and mastery of interdisciplinary knowledge integrating medicine and engineering. ConclusionThe RCF-based curriculum system effectively promotes the organic integration of medical and engineering knowledge, providing an internationally aligned competency-oriented paradigm for rehabilitation engineering talent cultivation, which holds significant value for broader application.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Objective To explore the change of serum chloride ion(Cl-)level and its relationship with prognosis in patients with acute heart failure(AHF).Methods A total of 289 patients with AHF admitted to the hospital from September 2020 to March 2023 were included in the study.Clinical and laboratory data of patients were collected,serum Cl-levels were detected at admission and discharge,and the difference of Cl-levels was calculated(△Cl-).Patients with AHF were divided into poor prognosis group and good prognosis group according to the incidence of adverse cardiovascular events during follow-up.Clinical and laboratory data of the two groups were compared.Logistic regression analysis was used to analyze the relationship between se-rum △Cl-level and poor prognosis of AHF by using restricted cubic spline(RCS)curve drawn by the func-tions in the rms package.Receiver operating characteristic(ROC)curve was plotted to analyze the value of△Cl-levels in predicting the risk of adverse cardiovascular events within 1 year of discharge from hospital in patients with AHF.Results The age and the proportion of patients with atrial fibrillation in the poor progno-sis group were higher than those in the good prognosis group,and the difference was statistically significant(P＜0.05).The levels of left ventricular ejection fraction(LVEF)and Cl-at discharge in the poor prognosis group were lower than those in the good prognosis group,and the levels of brain natriuretic peptide(BNP)and △Cl-in the poor prognosis group were higher than those in the good prognosis group,with statistical sig-nificance(P＜0.05).Logistic regression analysis showed that LVEF was an independent protective factor for poor prognosis of AHF,and age,BNP and △Cl-levels were independent risk factors for poor prognosis of AHF(P＜0.05).RCS curve analysis showed a significant linear association between △Cl-levels and the risk of adverse cardiovascular events in patients with AHF within 1 year of discharge.ROC curve analysis showed that the area under the curve of △Cl-level in predicting the risk of adverse cardiovascular events in AHF pa-tients within 1 year after discharge was 0.857,the sensitivity was 88.37％,and the specificity was 69.46％.Conclusion The change of serum Cl-level of patients with AHF is related to the prognosis of patients with AHF,and monitoring the serum Cl-level of patients with AHF can guide the early clinical intervention.

Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10％was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40％GMV features had the highest classification accuracy(82.50％),with sensitivity,specificity and area under the curve(AUG)of 85.05％,80.40％and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.

Objective:To investigate the clinical and pathological characteristics, treatment and prognosis of endometriosis (EM)-associated ovarian mesonephric-like adenocarcinoma (MLA).Methods:Clinical and pathological data were collected from nine patients diagnosed with EM-associated ovarian MLA at the Obstetrics and Gynecology Hospital of Fudan University between January 2022 and December 2024. Histological slides were re-reviewed, immunohistochemical examination and molecular testing were performed, and patient follow-up was conducted.Results:(1) Clinical characteristics: the median age of the nine patients was 54 years (range: 38-69 years). All patients presented with a pelvic mass; five cases also reported abdominal pain. Tumor location included five cases in the right ovary, two in the left ovary, and two involving both ovaries. International Federation of Gynecology and Obstetrics (FIGO) staging showed 3 cases at stage Ⅰ, 4 at stage Ⅱ, and 2 at stage Ⅲ. (2) Pathological features: gross examination revealed mixed solid-cystic masses with solid areas appearing gray-white or yellow-brown; the median maximum tumor diameter was 9.0 cm (range: 2.6-13.0 cm). Microscopically, tumors exhibited various architectural patterns, including tubular, glandular, papillary, slit-like, sex cord-like, glomeruloid, and solid structures, with tubular and glandular patterns being most common. Tumor cells demonstrated mild to moderate nuclear atypia. Of the 11 tumor foci in the 9 cases, 8 showed coexistence of MLA with other tumor components, such as endometrioid carcinoma, borderline endometrioid or borderline seromucinous tumors. In 1 case of MLA mixed with a borderline endometrioid tumor, both components exhibited squamous metaplasia. Immunohistochemistry showed variable expression of GATA-binding protein 3, thyroid transcription factor-1, CD 10, and calretinin, with positive rates of 9/11, 8/11, 5/11, and 3/6, respectively. Two tumor foci (2/11) exhibited focal expression of estrogen receptor and progesterone receptor. All cases displayed wild-type p53 expression. Molecular testing via next-generation sequencing in five patients revealed pathogenic mutations in the KRAS gene (5/5), with 3 cases (3/5) harboring additional pathogenic mutations in other genes. (3) Treatment and prognosis: all patients underwent surgery, supplemented by chemotherapy and (or) targeted therapy. Five patients underwent comprehensive staging surgery, four received cytoreductive surgery, and one patient received targeted therapy. The median follow-up duration was 7 months (range: 2-27 months). Three patients (3/9) experienced recurrence, and no deaths were reported during the follow-up period. Conclusions:EM-associated ovarian MLA demonstrates diverse morphological patterns and frequently coexists with other tumor types. Accurate diagnosis relies on an integrated evaluation of histomorphology, immunohistochemistry, and molecular testing. The primary treatment for EM-associated ovarian MLA is surgery, followed by adjuvant chemotherapy. Patients harboring pathogenic KRAS p.G12C mutations may benefit from targeted therapies. Ovarian MLA is an aggressive tumor, prone to recurrence in the short term, and has a poor prognosis.

Objective : To explore the mechanism of isorhamnetin (Iso) in the treatment of oral squamous cell carcinoma (OSCC) using network pharmacology and molecular docking methods and to verify it in vitro. Methods : The key targets were obtained by constructing the PPI protein interaction network based on the common intersection targets of Iso-OSCC. At the same time, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the related signaling pathways of the intersection targets. Iso and core targets were also analyzed through molecular docking and visualization. Colony formation assay and Transwell assay were used to identify the effect of Iso on the proliferation and invasion of Cal-27 cells. Western blot was used to analyze the regulatory effects of different concentrations of Iso on estrogen receptor-1 (ESR1), phosphoinositide-3-kinase regulatory subunit-1 (PIK3R1), Src tyrosine kinase (SRC), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins. Results: A total of 269 potential intersection targets of Iso-regulated OSCC were obtained. According to the degree obtained by topological analysis, PIK3R1, AKT1, SRC, ESR1, and other core targets were screened out. KEGG analysis showed that 165 signaling pathways were enriched in the intersection targets of Iso-OSCC, among which the PI3K/AKT signaling pathway played an important role in the treatment of OSCC with Iso. Molecular docking results showed that the absolute value of binding energy between target proteins PIK3R1, AKT1, SRC, ESR1, and Iso was high. After Cal-27 cells were treated with Iso, the number of cell colony formations, the number of transmembrane cells, and the expression of PIK3R1, ESR1, SRC, p-PI3K, and p-AKT were negatively correlated with the increase in Iso concentration (P < 0.05). Conclusion Iso can inhibit PI3K/AKT signal transduction and influence the expression of PIK3R1, AKT1, SRC, and ESR1 proteins, thereby inhibiting the occurrence and development of OSCC.