ObjectiveTo investigate the mechanism of action of modified Shaofu Zhuyutang in antagonizing cellular pyroptosis and fibrosis in ectopic endometrial tissues of endometriosis through the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3 （TRL4/NF-κB/NLPR3） signaling pathway. MethodsSeventy-two SPF-grade female SD rats were randomly divided into a sham-operated group （n = 12） and a modeling group （n = 60）. The rats in the sham-operated group underwent a caesarean section， while the rats in the modeling group were used to establish an endometriosis model through the auto-transplantation method. After successful modeling， the animals were randomly divided into the model group， progesterone group （0.25 mg·kg^-1）， and modified Shaofu Zhuyutang low-， medium-， and high-dose groups （7.5， 15， 30 g·kg^-1）， with 12 animals in each group. After 4 weeks of drug administration， voluntary activity and heat pain latency were observed. The rats were sacrificed for tissue collection， and Masson staining were used to observe histopathological changes in the endometrial tissues. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of interleukin-18 （IL-18）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） was used to detect the protein expression area of tumor necrosis factor-related factor 6 （TRAF6） and NLPR3 in the endometrial tissues. Immunofluorescence （IF） was used to detect the relative fluorescence intensity of Caspase-1 and gasdermin D （GSDMD） in the endometrial tissues. Western blot was employed to measure the relative expression of TRL4， myeloid differentiation factor 88 （MyD88）， TRAF6， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， and NLPR3 proteins in endometrial tissues. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 in the endometrial tissues. ResultsCompared with the sham-operated group， rats in the model group showed reduced voluntary activity and shorter heat pain latency. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were elevated. The relative expression areas of TRAF6 and NLPR3 proteins were increased， and the relative fluorescence intensity of Caspase-1 and GSDMD was enhanced. The relative expression of TRL4， MyD88， TRAF6， NF-κB p65， p-NF-κB p65， and NLPR3 proteins， along with the expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA， were significantly increased （P<0.01）. Compared with the model group， rats in the progesterone group and the modified Shaofu Zhuyutang medium- and high-dose groups exhibited improved voluntary activity， longer heat pain latency， the fibrosis of endometrial tissue is alleviated. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were decreased. The relative expression areas of TRAF6 and NLPR3 proteins decreased， and the relative fluorescence intensity of Caspase-1 and GSDMD weakened. The relative expression of TRL4， MyD88， TRAF6， p-NF-κB p65， NLPR3 proteins， and TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA expression were reduced （P<0.05， P<0.01）. ConclusionModified Shaofu Zhuyutang may play a therapeutic role in endometriosis by interfering with key proteins in the TRL4/NF-κB/NLPR3 signaling pathway， reducing NLRP3 inflammasome-induced cellular pyroptosis， antagonizing the fibrosis process in ectopic endometrial tissues， improving the inflammatory microenvironment in the pelvic cavity， and alleviating pain.

OBJECTIVE To explore the construction of selection system for drug directory of the county-level medical community based on multi-criteria decision analysis， and provide decision-making basis for the selection of drug directory of medical community. METHODS Taking county-level medical community in Chongqing as an example，Delphi method and analytic hierarchy process were employed to construct the selection system for drug directory of the county-level medical community. Selected drugs were quantitatively scored based on the constructed index system， and the drug directory was selected according to the drug’s comprehensive score. The implementation effect of the directory was then evaluated through questionnaire surveys one year after the implementation of the directory. RESULTS The expert authority coefficients of the two rounds of consultation were＞ 0.8， with Kendall’s W values of 0.213 and 0.196， respectively （P＜0.001）. Finally， the selection system for drug directory of the medical community was determined to include five evaluation dimensions： safety， effectiveness， economy， accessibility， and innovation， along with eight evaluation indicators. In the drug directory selected according to the above method， the proportions of centrally procured drugs， medical insurance drugs， and essential drugs had all increased compared to before the selection； the comprehensive scores of chemical drugs ranged from 50.25 to 96.31 scores， and the proportion of drugs scoring between 70 and 100 scores had increased from 78.06% before selection to 85.82%. Among them， antiparasitic drugs had the highest comprehensive scores， while drugs for the digestive tract and metabolism were the most numerous. The evaluation scores of each indicator and the comprehensive scores of drugs in the drug directory after the selection process increased significantly than before selection （P＜ 0.05）. CONCLUSIONS The selection system for drug directory of the county-level medical community constructed in this study is scientific， objective and operable. This process facilitates the promotion of standardized and unified management of drugs in the medical community.

Objective:To retrospectively analyze and study the clinical characteristics, imaging manifestations, laboratory tests, electroencephalography (EEG) results, immunotherapy efficacy, and prognosis of 48 patients with autoimmune encephalitis (AE) in the Hengyang area.Methods:Clinical data of 48 AE patients admitted to the First Affiliated Hospital, the Second Affiliated Hospital, and the Affiliated Nanhua Hospital, University of South China from January 2020 to April 2024 were collected. Retrospective analysis was conducted on age, gender, prodromal symptoms, initial symptoms, main clinical manifestations, cranial magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid routine biochemistry, serum and cerebrospinal fluid antibody detection results, and immunotherapy efficacy.Results:Among the 48 patients, there were 24 males and 24 females, with a median age of onset of 50 years. In terms of clinical manifestations, abnormal mental behavior is the most common initial symptom, accounting for 37.5%(18/48); The next was epileptic seizures, accounting for 35.4%(17/48); 16.7%(8/48) of patients experienced cognitive impairment; Rare initial symptoms included movement disorders, blurred vision, and loss of consciousness. In terms of neuroimaging, 47.9%(23/48) of patients had abnormal signals on cranial MRI, including 47.8%(11/23) of abnormal signals in the temporal lobe or hippocampus, 39.1%(9/23) in the frontal and parietal regions, 17.4%(4/23) in the occipital region, 13.0%(3/23) in the basal ganglia, and 8.7%(2/23) in the thalamus. In terms of EEG, 33.3%(16/48) of patients showed varying degrees of EEG abnormalities, manifested as diffuse slow waves, focal slow waves, epileptic like discharges, or increased fast waves. In terms of laboratory testing, 60.4%(29/48) of patients had routine biochemical abnormalities in cerebrospinal fluid, including elevated white blood cell count (>10×10 6 cells/L) in 33.3%(16/48), elevated protein (>0.45 g/L) in 37.5%(18/48), and elevated IgG in 33.3%(16/48). In terms of antibody testing, 27 cases were positive for antibodies, including 17 cases of N-methyl-D-aspartate receptor (NMDAR) antibody, 3 cases of anti-contactin associated protein 2 (CASPR2) antibody, 3 cases of anti-metabotropic glutamate receptors 5 (mGluR5) antibody, 2 cases of anti-dipeptidyl-peptidase-like protein (DPPX) antibody, 1 case of anti-GlyR antibody, and 1 case of anti-GAD65 antibody. In terms of treatment, 33 patients received immunotherapy on the basis of symptomatic treatment, and 13 of them showed improvement in clinical symptoms. Conclusions:The clinical manifestations of AE patients are highly heterogeneous, with typical initial clinical manifestations including mental abnormalities, epileptic seizures, cognitive and motor disorders. Neuroimaging changes are mainly in the temporal lobe or hippocampus, and antibody detection can timely confirm the diagnosis of AE. Early immunotherapy is the key to improving the prognosis of AE.

Objective:To investigate the application value of intrathoracic double-flap tech-nique (Kamikawa anastomosis) in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with esophagogastric junction cancer who were admitted to the First Affiliated Hospital of Xiamen University between July 2022 and April 2023 were collec-ted. There were 7 males and 3 females, aged 62(range, 53-71)years. All the 10 patients underwent combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer. Reconstruction was performed with an intrathoracic Kamikawa anastomosis. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3) follow-up and survival. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative and postoperative situations. All the 10 patients underwent surgery successfully. The operation time and volume of intraoperative blood loss were (347±41)minutes and (91±41)mL. The time to postoperative fluid diet intake, time to removal of postoperative abdominal drainage tube, time to removal of postoperative chest drainage tube, duration of postoperative hospital stay were (4.3±1.1)days, (5.0±1.6)days, (10.5±3.9)days, (13.3±3.8)days. Six patients had postoperative complications, including 1 case of Clavien-Dindo grade ⅢB, 3 cases of Clavien Dindo grade Ⅱ, 2 cases of Clavien Dindo grade Ⅰ. An upper gastrointestinal contrast at postoperative day 7 showed no anastomotic leak or anastomotic stricture in the 10 patients. (2) Postoperative pathological examination. Results of postoperative pathological examination in the 10 patients showed negative surgical margin. The number of lymph node dissected was 22±6. There were 3 patients with 5 positive lymph nodes. The tumor diameter and distance from center of tumor to squamocolumnar mucosal junction were (3.3±0.5)cm and (1.9±1.4)cm. One patient had tumor differentiation degree as high and moderate differentiation, 5 cases as moderate differentiation, 3 cases as moderate and low differentiation, 1 case as low differentiation. There were 5 patients with squamous cell carcinoma of the esophagogastric junction and 5 patients with adenocarcinoma of the esophagogastric junction. (3) Follow-up and survival. All the 10 patients were followed up for 7(range, 3?12)months, achieving disease-free survival. The visick quality of life grade Ⅰ, Ⅱ, Ⅲ, Ⅳ were observed in 7, 3, 0, 0 patients. Postoperative gastroscopy was completed in 7 patients, in which mild anastomotic strictures were noted in 2 patients, but no treatment was required. There was no reflux esophagitis.Conclusion:Intrathoracic Kamikawa anastomosis in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer is safe and feasible, with satisfactory short-term efficacy.

Global developmental delay/intellectual disability (GDD/ID) is an enormous group of neurodevelopmental disorders with diverse clinical and genetic heterogeneity. The estimated prevalence of GDD/ID was 1%-3%, affecting about 150 million people. GDD/ID is one of the leading causes of disability in children worldwide. The causes of GDD/ID are complex, comprising genetic and environmental factors. It is often co-morbid with a variety of psychiatric behavioral disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Owing to the improvement of genetic technology, monogenic GDD/ID has been one of the hot-spot research in genomic era, and the relevant preventive measures deserve extensive attention. In this review, we summarized the advances in genetics and prevention of monogenic GDD/ID.

Digital therapeutics(DTs)refers to a non-drug intervention method that uses electronic devices such as computers,smartphones,and wearable devices to evaluate and intervene through software programs and Internet technologies.It has been confirmed that there is a good therapeutic effect on a variety of mental disorders.Digital therapeutics can improve the insomnia problems of insomniacs,enhance the attention and work memory ability of patients with attention deficit hyperactivity disorder,and can also alleviate symptoms such as depression and anxiety disorder.Digital therapy will develop towards personalized treatment,popular treatment,fragmented treatment,and entertainment treatment in the future and have broad development prospects.

Background The operation mode of automobile manufacturing industry (AMI) makes workers have different degrees of occupational stress and burnout, which may lead to negative emotions and depressive symptoms. Objective To study the relationship between occupational stress, job burnout, and depressive symptoms in AMI workers. Methods In this study, 1300 workers from a Guangzhou AMI company were selected as subjects by cluster random sampling method. Occupational stress, job burnout, and depressive symptoms of the workers were assessed by using the Effort-Reward Imbalance (ERI) questionnaire, the Maslach Burnout Inventory general survey questionnaire, and the Patient Health Questionnaire-9, respectively. Hierarchical regression was used to analyze the effects of occupational stress and job burnout on depressive symptoms in AMI workers. Mediating effect model was used to analyze the mediating effect of job burnout on the relationship between occupational stress and depressive symptoms. Results There were 1300 questionnaires distributed, 1228 valid questionnaires collected, with a 94.5% recovery rate. The ERI ratio of 1228 AMI workers was 1.06±0.72, and the positive rate of occupational stress was 37.3% (458/1228). The score of job burnout was 2.18±1.37, and the positive rate of job burnout was 62.6% (769/1228). The score of depressive symptoms was 10.27±6.42, and the positive rate of depressive symptoms was 47.1% (578/1228). The dimensional scores of effort and over-commitment in occupational stress as well as emotional exhaustion and depersonalization in job burnout of AMI workers were positively correlated with the depressive symptom scores (r_s=0.415, 0.571, 0.573, 0.593, P＜0.05). The dimensional scores of reward and personal achievement were negatively correlated (r_s=−0.454, −0.339, P＜0.05). The percentages of variance in depressive symptoms score explained by occupational stress and job burnout were 26.7% and 16.6%, respectively. Job burnout had a partial mediating effect between the three dimensions of occupational stress and depressive symptoms, and the mediating effect values were −0.2832 (95%CI: −0.3250– −0.2434), 0.3553 (95%CI: 0.3071–0.4041), and 0.4193 (95%CI: 0.3681–0.4725), respectively. Conclusion AMI workers' occupational stress affects job burnout, but also indirectly affects depressive symptoms. Job burnout partially mediates the association between occupational stress and depressive symptoms. Reducing occupational stress and burnout levels of AMI workers may alleviate depressive symptoms.

Ideal osseointegration is intimately related to favorable osteoimmune properties around dental implants. An increasing number of in vitro and in vivo studies have indicated that the Hippo-YAP signaling pathway is involved in this biological process. In this article, the implicated roles of Hippo-YAP the signaling axis in peri-implant osteoimmunology were summarized by reviewing relevant evolving literature. The discrepancy concerning the Hippo-YAP signaling regulatory effect on osteogenesis and polarization direction were analyzed as well as propose the potential mechanism, which may be caused by the maturation of osteogenesis-related cells and heterogeneity of macrophages. More attention should be given to the requirements of promoting osteogenesis and patterns of regulating the immune microenvironment by Hippo-YAP in future studies.

Objective:To compare the clinical characteristics and prognosis of children with necrotizing pneumonia (NP) infected by bacteria and Mycoplasma pneumoniae (MP). Methods:The clinical data of 69 children with NP from January 2012 to June 2019 in Dalian Central Hospital Affiliated to Dalian Medical University were retrospectively analyzed. Among them, there were 27 cases of bacterial infection NP (bacterial infection group) and 42 cases of MP infection NP (MP group). The clinical symptoms and signs, extrapulmonary complications, laboratory examination, imaging examination, treatment, outcome and follow-up were compared between 2 groups.Results:There were no significant differences in the rale rate, respiratory tone reduction rate and total fever time between 2 groups ( P>0.05); the incidence of shortness of breath in bacterial infection group was significantly higher than that in MP group: 77.8% (21/27) vs. 14.3% (6/42), and there was statistical difference ( P<0.01). There were no significant differences in the incidence of extrapulmonary complications between 2 groups ( P>0.05). The white blood cell, C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL) -10 in bacterial infection group were significantly higher than those in MP group, the tumor necrosis factor (TNF)-α and interferon (IFN) -γ in bacterial infection group were significantly lower than those in the MP group, and there were statistical differences ( P<0.05). There were no significant differences in neutrophils, lactate dehydrogenase (LDH) and IL-6 between 2 groups ( P>0.05). The time of necrosis in bacterial infection group was significantly earlier than that in MP group: (14.5 ± 4.2) d vs. (21.7 ± 6.4) d, and there was statistical difference ( P<0.05); there was no significant difference in the incidence of pleural effusion between 2 groups ( P>0.05), but the incidence of pleural effusion separation in bacterial infection group was significantly higher than that in MP group: 70.4% (19/27) vs. 2.4% (1/42), and there was statistical difference ( P<0.01). There were no significant differences in antibiotic application time, CRP recovery time and hospital stay between 2 groups ( P>0.05); the oxygen uptake rate and closed thoracic drainage rate in bacterial infection group were significantly higher than those in MP group: 88.9% (24/27) vs. 35.7% (15/42) and 25.9% (7/27) vs. 11.9% (5/42), the recovery times of WBC and PCT in bacterial infection group were significantly longer than that in MP group: (12.8 ± 4.1) d vs. (9.2 ± 2.0) d and (10.5 ± 2.5) d vs. (7.6 ± 1.9) d, the bronchoalveolar lavage rate was significantly higher than that in MP group: 25.9% (7/27) vs. 76.2% (32/42), and there were statistical differences ( P<0.01 or <0.05). There was no significant difference in the absorption time of necrotic lesions between 2 groups ( P>0.05). Conclusions:Compared with MP infection, the clinical process of bacterial infection NP is serious, the necrosis time appears earlier, and the course of disease is longer. However, most of the children with NP can obtain a good prognosis after active symptomatic and antiinfective treatment.

Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.