ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

Background Perfluorinated and polyfluoroalkyl substances (PFAS), a large group of emerging pollutants, are ubiquitous in the ecological environment. Their multiple organ toxic effects on human body are reported. Understanding the exposure level of PFAS in cord serum and associated influencing factors can provide scientific evidence for studying maternal and newborn health effects and risk regulation. Objective To explore the exposure levels of PFAS in cord serum and potential impact factors. Methods This study was based on the maternal and infant database and the cord serum sample bank of the Sheyang Mini Birth Cohort Study (SMBCS) established in 2009. A self-designed questionnaire was used to collect information on sociodemographic characteristics, living environment, and lifestyle of mothers during pregnancy. A total of 1097 cord serum samples were measured utilizing ultra-high performance liquid chromatography-Q-Exactive Orbitrap high-resolution mass spectrometry. Multiple linear regression models were used to identify influencing factors related to PFAS exposure level in cord serum. Results A total of 38 types of PFAS were detected in the cord serum samples, including 20 perfluorocarboxylic acids (PFCA), 14 perfluorosulfonic acids (PFSA), and 4 other types of PFAS. The detection rates of 14 PFAS compounds were above 50%. The detection rates of perfluoro-1-hexanesulfonic acid (PFHxS), perfluoro-1-octanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA) were in the range of 99.18%-100.00%. The median concentrations of PFOA and 6∶2 chlorinated polyfluorinated ether sulfonic acid (6∶2CI-PFESA) were higher than those of the other compounds, which were 3.76 µg·L⁻¹ and 2.61 µg·L⁻¹, respectively. The correlation coefficients among cord serum PFAS were in the wide range of 0.0911-0.8429 (P < 0.05). The associations between PFHxS and perfluoro-1-heptanesulfonic acid (PFHpS) (r=0.8429, P < 0.05), PFOS and PFHpS (r=0.7012, P < 0.05), and PFUdA and perfluorododecanoic acid (PFDoA) (r=0.7875, P < 0.05) were positive. The proportions of PFCA and PFSA in the cord serum samples were 60.1% and 38.4%, respectively. PFOA and 6∶2 Cl-PFESA were the predominant compounds in the cord serum samples, whose proportions were 37.8% and 19.3%, respectively. The concentrations of specific types of cord serum PFAS had varied associations with the following demographic variables of pregnant women: age, parity, education level, gestational age, and occupation. The multiple linear regression analysis found that the concentrations of 8 PFAS (PFHxS, PFHpS, PFNA, PFOS, PFDA, PFUdA, PFDoA, and 6∶2 CI-PFESA) in umbilical cord serum were lower in pregnant women aged 25 years and older than in those under the age of 25 years; compared to pregnant women with education levels at or below junior middle school, those with education levels at or above high school had lower concentrations of perfluoroheptanoic acid (PFHpA); the concentration of PFHpA in cord serum was negatively correlated with household annual income; multiparous women had higher concentrations of PFNA, PFUdA, and PFDoA than primiparous women; compared to mothers engaged in manual labor, the concentration of perfluoro-1-butanesulfonic acid (PFBS) in umbilical cord serum was lower in mothers engaged in mental labor, while the concentrations of PFBS and PFOA were lower and the concentrations of perfluorotridecanoic acid (PFTrDA) and 8∶2 chlorinated polyfluorinated ether sulfonic acid (8∶2CI-PFESA) were higher in mothers of other occupational types; the concentrations of umbilical cord serum PFOA, PFOS, PFUdA, and PFDoA were positively correlated with the gestational age of pregnant women, while N-methylperfluoro-1-octanesulfonamido acetic acid (N-MeFOSAA) was negatively correlated with the gestational age of pregnant women; PFTrDA was negatively correlated with the birth weight of newborns; compared with those with insufficient gestational weight gain, those with adequate gestational weight gain had lower PFDoA, while those with excess gestational weight gain had higher N-MeFOSAA. Conclusion PFAS compounds exposure is common in the mothers and infants in the study area. PFOA and 6∶2 CI-PFESA are the two main compounds in cord serum. Cord serum PFAS are associated with several demographic characteristics of the pregnant women. Future research needs to pay more attention to PFAS alternatives and other emerging contaminants.

Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.

Objective To study the inhibitory effect of Huidu Yinhua powder from the Orthodox Manual of External Medicine on methicillin-resistant Staphylococcus aureus(MRSA),virulence factor α-hemolysin(Hla)activity,and biofilm formation,and to explore the optimal ratios of Huidu Yinhua powder and provide experimental support for its use.Methods The inhibitory effects of Huidu Yinhua powder and the herbs in the formula on USA300 were analyzed by the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and disk diffusion assay(K-B method).Hemolysis,neutralization,oligomerization,and Western blot assays were used to verify in which form the drug inhibits the activity of virulence factor α-hemolysin(Hla).A biofilm assay was performed to evaluate the inhibitory effect of Huidu Yinhua powder on biofilm.Orthogonal experiments were performed to explore the optimal ratio of Huidu Yinhua powder.Results Huidu Yinhua powder inhibited the MRSA strain with a MIC90 of 64 mg/mL and an MBC of 256 mg/mL with antibacterial circle diameter of(7.50±0.50)mm.Huidu Yinhua powder inhibited Hla activity by inhibiting Hla secretion.The minimum effective concentration(MEC)was 16 mg/mL,and the MEC of biofilm was 8 mg/mL.In Huidu Yinhua powder,honeysuckle and astragalus only affected the hemolytic activity of MRSA and biofilm formation without inhibiting bacterial growth.The hemolytic activity and biofilm of MEC were both 32 mg/mL.Glycyrrhiza had a strong bacterial inhibitory capacity with a MIC90 of 8 mg/mL and biofilm MEC of 1 mg/mL without showing inhibitory hemolytic activity at subinhibitory concentrations.The orthogonal experiment showed that,at a ratio of honeysuckle,astragalus,and glycyrrhiza in Huidu Yinhua powder of 1∶2∶4,the MIC90 was 16 mg/mL,MEC of hemolytic activity was 8 mg/mL and that of biofilm was 4 mg/mL,both of which were the lowest among the nine groups.Conclusions Huidu Yinhua powder affects the hemolytic activity and biofilm formation of MRSA at subinhibitory concentrations with the optimal ratio of honeysuckle,astragalus,and glycyrrhiza being 1∶2∶4.

ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction （Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex） in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control， model， fluoxetine， and low-， medium-， and high-dose （5.36， 10.71， 21.42 g·kg^-1， respectively） Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress （CUMS）. The sucrose preference test （SPT） was carried out to examine the sucrose preference of rats. Forced swimming test （FST） was carried out to measure the immobility time of rats. The open field test （OFT） was conducted to measure the total distance， the central distance， the number of horizontal crossings， and the frequency of rearing. Morris water maze （MWM） was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase （iNOS， the polarization marker of M1 microglia） and CD206 （the polarization marker of M2 microglia）. Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS， CD206， pro-inflammatory cytokines ［tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6］ and anti-inflammatory cytokines （IL-4 and IL-10） in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group， the model rats showed a reduction in sucrose preference （P<0.05）， an increase in immobility time （P<0.05）， decreased motor and exploratory behaviors （P<0.05）， and weakened learning and spatial memory （P<0.05）. In addition， the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β， IL-6， and TNF-α （P<0.05）. Compared with the model group， Baihuan Xiaoyao decoction increased the sucrose preference value （P<0.05）， shortened the immobility time （P<0.01）， increased the motor and exploratory behaviors （P<0.05）， and improved the learning and spatial memory （P<0.01）. Furthermore， the decoction down-regulated the positive expression and protein level of iNOS， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted the positive expression of CD206， and elevated the levels of IL-4 and IL-10 （P<0.01） in the hippocampus of the high dose group. Moreover， the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value （P<0.01）， shorter immobility time （P<0.01）， longer central distance （P<0.01）， stronger learning and spatial memory （P<0.01）， higher positive expression and protein level of iNOS （P<0.01）， lower levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， lower positive expression and mRNA level of iNOS （P<0.05）， and higher levels of IL-4 and IL-10 （P<0.05， P<0.01） than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Objective:To automatically classify hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) based on mul-titask learning algorithm using native T1 mapping images.Methods:A total of 203 patients admitted to Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2017 to December 2021 were enrolled, including 53 patients with HHD, 121 patients with HCM, and 29 patients with normal control (NC). Native T1 mapping images of all enrolled patients were acquired using MRI and processed by a multi-task learning algorithm. The classification performance of each model was validated using ten-fold crossover, confusion matrix, and receiver operator characteristic (ROC) curves. The Resnet 50 model based on the original images was established as a control.Results:The ten-fold crossover validation results showed that the MTL-1 024, MTL-64, and MTL-all models showed better performance in terms of area under the curve (AUC), accuracy, sensitivity, and specificity compared to the Resnet 50 model. In the classification task, the MTL-64 model showed the best performance in terms of AUC (0.942 1), while the MTL-all model reached the highest value in terms of accuracy (0.852 2). In the segmentation task, the MTL-64 model achieved the best results with the Dice coefficient (0.879 7). The confusion matrix plot showed that the MTL model outperforms the Resnet 50 model based on the original image in terms of overall performance. The ROC graphs of all MTL models were significantly higher than the original image input Resnet 50 model.Conclusions:Multi-task learning-based native T1 mapping images are effective for automatic classification of HHD and HCM.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease.Methods:From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease.Results:In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio ( HR) value of 0.81 (95% CI: 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95% CI: 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95% CI: 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions:In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.