ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Objective To investigate the application efficiency and potential of CT radiomics in differentiating malignant and benign sub-centimeter solid pulmonary nodules. Methods A retrospective study was performed on the sub-centimeter ( ≤ 10 mm) solid pulmonary nodules detected by enhanced CT in our hospital from March 2020 to January 2023. Malignancy was confirmed by surgical pathology, and benignity was confirmed by surgical pathology or follow-up. Lesions were manually segmented and radiomic features were extracted. The feature dimension was reduced via feature correlation analysis and least absolute shrinkage and selection operator (LASSO). The 5-fold cross validation was used to validate the model. Support vector machine, logistic regression, linear classification support vector machine, gradient boosting, and random forest models were established for CT radiomics. Receiver operating characteristic curves were drawn. Delong test was used to compare the diagnostic performance of the five classifiers. The optimal model was selected and compared to radiologists with medium and high seniority. Results A total of 303 nodules, 136 of which were malignant, were examined. Radiomics models were established after feature extraction and selection. On test set, the areas under the receiver operating characteristic curves of support vector machine, logistic regression, linear classification support vector machine, random forest, and gradient boosting models were 0.922 (95%CI: 0.893, 0.950), 0.910 (95%CI: 0.878, 0.942), 0.905 (95%CI: 0.872, 0.938), 0.899 (95%CI: 0.865, 0.933), and 0.896 (95%CI: 0.862, 0.930), respectively. Delong test indicated no significant differences in the performance of the five radiomics models, and the support vector machine model showed the highest accuracy and F1 score. The support vector machine model showed significantly higher diagnostic accuracy as compared to radiologists (83.8% vs. 55.4%, P < 0.001). Conclusion The radiomics models achieved high diagnostic efficiency and may help to reduce the uncertainty in diagnosis of malignant and benign sub-centimeter solid nodules by radiologists.

Objective To explore the mechanism of protective effect of Jianpi Yichang Powder on intestinal mucosa by observing its effect on the expression of autophagy-related molecules in colon of ulcerative colitis(UC)model rats.Methods SD rats were randomly divided into normal group,model group,Jianpi Yichang Powder group and sulfasalazine group.UC rat model was established by 2,4,6-trinitrobenzene sulfonic acid/ethanol solution.After the model was successfully reproduced,the rats were given drugs orally once a day for 14 days.The general condition of rats was observed and the disease activity index(DAI)score was calculated.The pathological morphology of colonic tissue in all groups was observed by hematoxylin eosin(HE)staining.Autophagy of colonic epithelial cells was examined by transmission electron microscope.The expressions of myosin-like BCL2 interacting protein(Beclin1)and microtubule-associated protein 1 light chain 3(LC3)in colonic tissue were detected by immunofluorescence staining and Western Blot.The mRNA expressions of autophagy protein 5(Atg5),autophagy protein 7(Atg7)and ubiquitin-binding protein 62(p62)were detected by real-time quantitative polymerase chain reaction(Real-time PCR).Results Compared with the normal group,the general situation of the model group was worse,and the DAI score increased significantly(P<0.000 1).There was obvious epithelial cell damage in colonic tissue,and the number of autophagosomes decreased obviously under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue decreased significantly(P<0.000 1),while the expression of p62 mRNA increased significantly(P<0.000 1).Compared with the model group,the general condition of rats in Jianpi Yichang Powder group had recovered significantly,and the DAI score decreased significantly(P<0.000 1).Pathological damage of colonic tissue has been improved in different degrees,and the number of autophagosomes increased significantly under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue were significantly increased(P<0.01,P<0.001,P<0.000 1),while the expression of p62 mRNA was significantly decreased(P<0.01).Conclusion Jianpi Yichang Powder can protect UC colon mucosa from injury by up-regulating the expression of autophagy-related molecules including Beclin1,LC3,Atg5 and Atg7,down-regulating the expression of p62 and enhancing autophagy.

Objective To observe the effects of Simo Decoction on the expressions of vasoactive intestinal peptide(VIP)and its receptor 2(VIPR2)in rats with functional dyspepsia(FD)of liver and spleen stagnation syndrome;To investigate its mechanism of action in regulating gastrointestinal motility.Methods Totally 60 SD rats were randomly divided into blank group,model group,mosapride group(0.305 mg/kg)and Simo Decoction high-,medium-and low-dosage groups(5.62,2.81,1.40 g/kg).The liver and spleen qi stagnation FD rat model was prepared by multifactorial modeling method,and the corresponding drugs were given by gavage for 14 days.The general conditions of rats in each group were observed,and body mass,gastric emptying rate and small intestine propulsion rate were measured;the histological structure of gastric antrum tissue and duodenal tissue were observed by HE staining;the positive expressions of VIP and VIPR2 in duodenal tissue were observed by immunohistochemistry;the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue were detected by Western blot and RT-PCR,respectively.Results Compared with the blank group,the general condition of the rats in model group was poorer,body mass,gastric emptying rate and small intestine propulsion rate were significantly lower(P<0.01),and the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue significantly increased(P<0.05,P<0.01).Compared with the model group,the body mass,gastric emptying rate and small intestine propulsion rate in Simo Decoction high-and medium-dosage groups and the mosapride group significantly increased(P<0.05,P<0.01),and the protein and mRNA expressions of VIP and VIPR2 in duodenal tissue significantly decreased(P<0.05,P<0.01).HE staining showed no significant changes in the morphology of gastric antrum and duodenum tissues.Conclusion Simo Decoction may promote gastrointestinal motility by inhibiting the expressions of VIP and VIPR2 in duodenal tissue of FD rats with liver and spleen qi stagnation,thereby improving FD.

Objective To investigate the effects of Jianpi Yichang Powder on regulating the NLRP3 inflammasome signaling pathway to inhibit dendritic cells(DCs)inflammatory injury induced by TNF-α;To explore its mechanism in the treatment of ulcerative colitis.Methods C57BL/6 mice DCs were primitively isolated and cultured.The cultured DCs were randomly divided into the normal group,model group,negative control group,positive drug group and TCM group.DCs inflammatory microenvironment model was established by TNF-α induction.After corresponding treatments were given to each group,CCK-8 method was used to detect cell proliferation ability,immunofluorescence and Western blot were used to detect the protein expressions of NLRP3,ASC and Caspase-1 in DCs respectively,Western blot and RT-PCR were used to detect the protein and mRNA expressions of IL-1β and IL-18 in DCs.Results Compared with the normal group,the proliferation ability in DCs of model group significantly decreased(P<0.01),the positive expressions of NLRP3,ASC and Caspase-1 significantly increased,the expressions of NLRP3,ASC,Caspase-1,IL-18,IL-1β protein and IL-18,IL-1β mRNA in DCs significantly increased(P<0.01).Compared with the model group and negative control group,the proliferation ability of DCs significantly increased in positive drug group and TCM group(P<0.01),the positive expressions of NLRP3,ASC,and Caspase-1 significantly decreased(P<0.01),the protein expressions of NLRP3,ASC,Caspase-1,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01),and the mRNA expressions of IL-1β and IL-18 significantly decreased(P<0.01).The cell proliferation ability,Caspase-1 positive expression,and IL-18 mRNA expression of TCM group were significantly higher than those of the positive drug group(P<0.05),while the mRNA expression of IL-1β was lower than that of the positive drug group(P<0.05).Conclusion Jianpi Yichang Powder can inhibit the inflammatory response of DCs induced by TNF-α,and its mechanism in the treatment of ulcerative colitis may be related to regulating the expressions of the NLRP3 inflammasome signaling pathway,including the expressions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β.

During natural viewing, we often recognize multiple objects, detect their motion, and select one object as the target to track. It remains to be determined how such behavior is guided by the integration of visual form and motion perception. To address this, we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task. We found that pursuit responses were biased toward the motion direction of a target with a hole. By computing the relative weighting, we found that the target with a hole exhibited a larger weight for vector computation. The global hole feature dominated other form properties. This dominance failed to account for changes in pursuit responses to a target with different forms moving singly. These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.
Animals ; Pursuit, Smooth ; Macaca mulatta ; Motion Perception/physiology* ; Photic Stimulation

OBJECTIVE To explore the improvement effect and mechanism of Simotang oral liquid on functional dyspepsia （FD） model rats by regulating PTEN-induced putative kinase 1 （Pink1）/E3 ubiquitin ligase （Parkin） axis. METHODS SD male rats were subjected to unpredictable chronic stress to establish an FD model， and were randomly grouped into the model group， positive control group （Domperidone tablets， 3.5 mg/kg）， Simo decoction group （Simotang oral liquid， 5.4 mL/kg）， with 20 rats in each group. The blank group without modeling was set up. Administration groups were given relevant medicine intragastrically， blank group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 14 d. After the last administration， the gastric emptying rate and small intestine propulsion rate of rats were detected. The contents of gastrointestinal hormones [motilin （MTL）， gastrin （GAS） and cholecystokinin （CCK）] in rats were determined； the mitochondrial structure of ICC in gastric antrum tissue of rats was observed； the immunofluorescence co-localization method was applied to observe the expression of cytochrome C oxidase Ⅳ （COX Ⅳ） and Parkin in gastric antrum tissue of rats； the protein expressions of LC3， p62， Pink1 and Parkin in gastric antrum tissue of rats were all detected. RESULTS Compared with the blank group， the gastric emptying rate， small intestinal propulsion rate， the serum contents of MTL and GAS， and protein expression of p62 in model group were all reduced significantly （P＜0.05）； the serum content of CCK， the co-localization expression of COX Ⅳ and Parkin in mitochondria， the protein expressions of LC3， Pink1 and Parkin were all increased significantly （P＜0.05）. The number of ICC mitochondria in gastric antrum tissue decreased， mitochondria became vacuolated， mitochondrial cristae were blurry， and there were more autophagic lysosomes. Compared with the model group， the above indexes of the positive control group and the Simo decoction group were reversed significantly （P＜0.05）； the mitochondrial structure of ICC gradually recovered， with clear mitochondrial cristae and reduced autophagic lysosomes. CONCLUSIONS Simotang oral liquid can improve gastrointestinal motility and gastrointestinal hormone levels in model rats， the mechanism of which may be related to inhibiting Pink1/Parkin axis and blocking autophagy.

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.

The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*