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

Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.

BACKGROUND:Our previous studies found that adding barium sulfate could improve the mechanical and radiopaque properties of calcium phosphate cement.However,with the degradation of calcium phosphate,the remaining radiopaque agent is difficult to degrade,and the space-occupying and osteoclast effects at the implantation site affect the bone repair process.Therefore,it is necessary to develop a new biodegradable radiopaque material. OBJECTIVE:To discuss the radiopaque ability of bioactive degradable material strontium polyphosphate(SrPP)and its impact on the physicochemical properties and osteogenic effect of calcium phosphate cement. METHODS:(1)Calcium phosphate cement(CPC),starch modified calcium phosphate cement(CPS)and starch modified calcium phosphate cement(20%SrPP-CPN)containing SrPP(20%mass fraction of bone cement powder)were prepared respectively,and the physicochemical properties of the three groups of bone cements were characterized.(2)The three groups of bone cement extracts were co-cultured with rat bone marrow mesenchymal stem cells,respectively,to detect cell proliferation,energy metabolism,and osteogenic differentiation.(3)Bone defects with a diameter of 5 mm were made on each side of the top of the skull of 24 SD rats,and they were randomly divided into control group(without any intervention),CPC group,CPS group,and 20%SrPP-CPN group for intervention,with 6 rats in each group.Relevant tests were performed after 4 and 12 weeks of intervention. RESULTS AND CONCLUSION:(1)Compared with the other two groups of bone cement,20%SrPP-CPN had enhanced radiopaque ability,increased compressive strength and degradation rate,and prolonged curing time,and 20%SrPP-CPN could release Sr2+ stably during degradation.(2)CCK-8 assay showed that 20%SrPP-CPN did not affect the proliferation of bone marrow mesenchymal stem cells.Cell starvation test(serum-free culture)showed that 20%SrPP-CPN could promote the proliferation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.Compared with the other two groups of bone cements,20%SrPP-CPN increased adenosine triphosphate concentration in bone marrow mesenchymal stem cells.Alkaline phosphatase and alizarin red staining showed that 20%SrPP-CPN could promote osteogenic differentiation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.(3)In the rat skull defect experiment,Micro-CT scanning and histological observation(hematoxylin-eosin and Masson stainings)showed that bone cement in 20%SrPP-CPN group was significantly degraded compared with that in CPC and CPS groups,and a large number of new bone tissues were dispersed in degraded bone cement.Immunohistochemical staining showed that Runx2 protein expression was increased in 20%SrPP-CPN group compared with CPC group and CPS group(P＜0.01).(4)These results show that 20%SrPP-CPN has good radiopaque ability and osteogenic properties.

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.

Objective: To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA). Methods: Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA. Results: After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P < .001). After applying acupuncture, the levels of 5-HT, HA, and SP at skin acupoints were lower than those in the model group (all P < .05), and tryptase level was higher (both P < .05). Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint (P = .004). Compared with the model group, the serum levels of IL-1β, IL-6, and TNF-α in the MAR-SJ 10 and MAL-SJ 10 groups were lower (all P < .05). Conclusion Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidirectionally regulate local MCs of these acupoints. This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment, but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.

Objective: To evaluate the preventive effect of implementing the free influenza vaccination policy on school absence among primary and secondary school students, so as to provide a reference for formulating and adjusting vaccination strategies. Methods: Among primary and secondary school students aged 6 to 18 in Longgang District, Shenzhen, they were divided into a vaccinated group (265 996 students) and an unvaccinated group (122 513 students) according to their influenza vaccination history during November 2023. Propensity score matching was used to conduct a 1∶1 match between the two groups to balance covariates. The number of absences per month was set as the dependent variable to construct a difference in differences model, and Poisson regression was employed to analyze the overall and multi time point effects. Results: Vaccination against influenza was associated with low rate of absenteeism among primary and secondary school students, with an overall preventive effect of 26.52% (95% CI = 23.47% -29.45%). The preventive effects in November (the month of vaccination) and December 2023, January and March 2024 were 42.12%, 40.12%, 30.33% and 20.91%, respectively. The preventive effect of the influenza vaccine on absenteeism among primary school students (26.39%) was not significantly different from that among secondary school students ( 27.97% ) ( P >0.05). The regression coefficient for class vaccination rates ranged from 0.998 to 0.999 ( P <0.01), indicating that for every 10% increase in influenza vaccination rates, absenteeism could be reduced by 1.5% to 2.2%. Conclusion Implementing free influenza vaccination for primary and secondary school students might help to reduce the risk of absenteeism, yielding significant socioeconomic benefits.