Endometriosis （EMT） is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea， pelvic mass， and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease， which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However， the pathogenesis of EMT is still not completely clear， and the disease has a long course. Therefore， developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine （TCM）， while the underlying mechanism remains in exploration. Programmed cell death （PCD） is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis， which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM， which regulates PCD via multiple pathways， routes， targets， and mechanisms. However， the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes （apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis）， with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.

Objective To investigate the molecular mechanism of lectin-like oxidized low-density lipoprotein receptor 1(LOX-1)in the regulation of high glucose induced phagocytosis dysfunction of mouse microglia(BV2 microglia).Methods BV2 cells were cultured in vitro,lentivirus LOX-1RNAi vector(LV-LOX-1)and lentivirusempty vector(LV-Con)were constructed and divided into normal control(NC)group,HG group,LV-LOX-1 group and LV-Con group.After infecting BV2 cells with LV-LOX-1 and LV-Con,the cells were cultured with 25 mmol/L glucose for 24 h,and then divided into HG+LV-LOX-1 group and HG+LV-Con group.After treatment of HG+LV-LOX-1 and HG+LV-Con infected BV2 microglia with 15 μmol/L FH535(β-catenin inhibitor)and AEBSF(ATF6α inhibitor)for 24 h,respectively,they were denoted as HG+LV-LOX-1+FH535 group,HG+LV-Con+FH535 group,HG+LV-LOX-1+AEBSF group,and HG+LV-Con+AEBSF group.Transfection efficiency was determined by fluorescence microscopy,RT-PCR and Western blot.Cell viability was detected b CCK-8.RT-PCR and Western blot were used to detect the mRNA and protein expression of LOX-1,β-catenin,ATF6α and milk fat globular-surface growth factor Ⅷ(MFG-E8)in each group.Results After 72 h of LV-LOX-1 infection,the cells in LV-LOX-1 and LV-Con groups showed a lot of green fluorescence,but not in NC group.Compared with NC group,the mRNA and protein expression of LOX-1 and ATF6α were increased(P<0.05),while the mRNA and protein expression of MFG-E8 and β-catenin decreased in HG group(P<0.05).Compared with HG+LV-Con group,the mRNA and protein expression of LOX-1 and ATF6α were decreased(P<0.05),while the mRNA and protein expression of MFG-E8 and β-catenin increasedin HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,the mRNA and protein expressions of MFG-E8 and β-catenin were decreased(P<0.05),and the mRNA and protein expressions of ATF6α and p-β-catenin and p-ATF6α were increased in HG+LV-LOX-1+FH535 group(P<0.05).Compared with HG+LV-LOX-1 group,the mRNA and protein expression were increased(P<0.05),ATF6α mRNA and protein expression and p-ATF6α protein expression were decreased MFG-E8 in HG+LV-LOX-1+AEBSF group(P<0.05).Conclusions LOX-1,MFG-E8,β-catenin and ATF6α are involved in the regulation of phagocytosis of BV2 cells.LOX-1 promotes the phagocytosis dysfunction of BV2 microglia induced by high glucose through β-catenin/ATF6α signaling pathway.

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g^-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

Objective To explore the impact of nurse-led multidisciplinary collaborative nutrition inter-vention on the nutritional indicators in the patients with stroke.Methods A total of 100 patients with stroke admitted in this hospital from January to December 2020 were selected as the study subjects and divided into the observation group and control group by the propensity score matching,50 cases in each group.The control group was given the traditional nutrition intervention,and the observation group was given the nurse-led mul-tidisciplinary cooperative nutrition intervention.The blood,nutritional and biochemical indicators,physique monitoring indicators and nutritional risk indicators were compared between the two groups.Results The levels of total protein(TP),albumin(ALB),hemoglobin(Hb),prealbumin(PAB),body mass index(BMI),upper arm muscle circumference(AMC)and triceps skin fold thickness(TSF)on 21 d after admission in both groups were increased compared with those on 2,15 d after admission,and which on 15 d after admission were higher than those on 2 d after admission(P＜0.05),moreover the above indicators levels on 15,21 d after ad-mission in the observation group were higher than those in the control group,and the differences were statisti-cally significant(P＜0.05).Body mass index(BMI),upper arm circumference(AMC)and triceps skinfold thickness(TSF)in both groups on 21 d of admission were higher than those on 2,15 d of admission(P＜0.05).The nutritional risk screening 2002(NRS2002)score on 21 d after admission in the two groups were decreased compared with those on 2,15 d after admission,while which on 15 d after admission was decreased compared with that on 2 d after admission,moreover the NRS2002 score on 15,21 d after admission in the ob-servation group were lower than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion Giving the nurse-led multidisciplinary cooperative nutrition intervention could im-prove the blood nutritional and biochemical indicators and physique monitoring indicators,and reduce the nu-tritional risk of the patients with stroke.

Objective:To explore the prognostic value of baseline 18F-FDG PET/CT metabolic parameters in locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). Methods:From September 2015 to October 2021, the clinical data of 180 LACC patients (age: 22-76 years) who underwent 18F-FDG PET/CT before CCRT at Affiliated Cancer Hospital of Shandong First Medical University were analyzed retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUV max, and SUV mean were computed by using the margin threshold of 42%SUV max. The optimal threshold for predicting progression-free survival (PFS) was obtained by ROC curve analysis. The Kaplan-Meier method was applied for survival analysis, and the log-rank test was applied to compare the survival rate between groups. Multivariate Cox proportional hazard regression was used to analyze progression for PFS. Results:The median follow-up was 19.1 months, and 54 patients (30.0%, 54/180) suffered from disease progression. ROC curve analysis showed that the optimal cut-off value of MTV was 31.145 ml, with the AUC of 0.641. Para-aortic lymph node (PALN) metastasis had the highest AUC value (0.589) among the clinical factors, followed by International Federation of Gynecology and Obstetrics (FIGO) stage (0.581). The 1-year PFS rates of patients with MTV<31.145 ml ( n=88) and MTV≥31.145 ml ( n=92) were 80.68% and 59.78%, respectively ( χ2=13.72, P<0.001). Multivariate Cox analysis demonstrated that pathological type (hazard ratio ( HR)=3.075, 95% CI: 1.370-6.901, P=0.006), FIGO stage ( HR=1.955, 95% CI: 1.031-3.707, P=0.040), PALN metastasis ( HR=2.136, 95% CI: 1.202-3.796, P=0.010) and MTV ( HR=2.449, 95% CI: 1.341-4.471, P=0.004) were the significant predictors for PFS. Conclusions:Pathological type, FIGO stage, PALN metastasis and MTV are independent prognostic risk factors for PFS. MTV as the baseline 18F-FDG PET/CT metabolic parameter, can realize prognostic stratification analysis.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

OBJECTIVE To explore the impact and mechanism of curcumin on endometriosis （EMS） model rats based on Notch1 signaling pathway. METHODS Female SD rats with synchronized estrous cycles were implanted with autologous endometrium on the abdominal wall to construct EMS model. EMS rats were randomly divided into model group， low-， medium- and high-dose groups of curcumin （60， 120， 240 mg/kg）， and Notch 1 inhibitor DAPT group （7 mg/kg）. The sham surgery group was also established， with 10 rats in each group. Rats in each group received intragastric administration or injection via caudal veins with the corresponding drugs for 4 weeks. Endometriotic lesions were observed and measured using ultrasound and visual inspection， and their volumes were calculated. Histopathological morphology of the lesion tissues was observed. The levels of interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the abdominal cavity fluid， as well as the mRNA and protein expression levels of Notch1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor （VEGF） in the endometriotic lesions were measured. RESULTS Compared with the model group， the volume of endometriotic lesions in the low- ， medium- and high-dose groups of curcumin and the DAPT group was significantly decreased （P＜0.05）； atrophy or disappearance of columnar epithelium， cyst disappearance； the levels of IL-1β， IL-6， and TNF- α （except for the low-dose curcumin group） in the abdominal cavity fluid， as well as the mRNA （except for MMP-9 and VEGF in the low-dose curcumin group） and protein （except for MMP-9 in the low-dose curcumin group） expression levels of Notch1， MMP-9， and VEGF in the endometriotic lesions were significantly decreased （P＜0.05）. The curcumin high-dose group and DAPT group showed superior results in most indicators compared to the curcumin low- and medium-dose groups. CONCLUSIONS Curcumin has an improving effect on EMS， and its mechanism may be related to inhibiting Notch1 signaling pathway， reducting local inflammatory responses， and inhibiting ectopic endometrial invasion and angiogenesis.