ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.

In recent years, with the large-scale use of plastic products, the degree of plastic pollution has increased, becoming a serious global problem. Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, are widely found in organisms and the environment. These plastic particles enter the human body through 3 exposure pathways: breathing, the food chain’s bioaccumulation and transfer, and skin contact, thereby exerting toxic effects. The physical attributes of MNPs, including their shape, size, and surface characteristics, are not static but rather undergo dynamic transformations in response to changing environmental conditions. These changes can significantly influence their behavior and interactions within different ecosystems. When considering MNPs as carriers of chemicals, two primary mechanisms can be distinguished. (1) MNPs have the capacity to adsorb pollutants from their surrounding environment. These pollutants may encompass a wide range of substances, such as heavy metals, organic compounds, and other contaminants that are commonly found in water, soil, or air. (2) MNPs may also carry chemical agents that are artificially introduced during their commercial production process. For example, flame retardants and pigments are often added to plastics to enhance their performance or appearance. These artificially added chemicals can remain associated with MNPs throughout their lifecycle and may contribute to their overall toxicological impact. Cardiovascular diseases (CVDs) are a general term for diseases of the heart, arteries, veins, and capillaries, and are one of the main causes of disability and death. CVDs have higher incidence, mortality, and recurrence rates, and more complications, which reduce the quality of life and happiness of patients, the phenomenon is gradually showing a trend of early onset, therefore early-stage prevention for CVDs is of critical importance. This article reviews the properties of MNPs and their potential threats to the cardiovascular system, aiming to explore how MNPs cause CVDs through certain physiological effects, toxicity mechanisms, and related pathways. Our review primarily focus on elucidating several critical mechanisms through which MNPs exert their adverse effects. Specifically, the review examines how the enhancement of oxidative stress can trigger the expression of pro-inflammatory factors, which in turn leads to the formation of a chronic inflammatory microenvironment within biological systems. Additionally, MNPs possess the capacity to adsorb toxic metals and organic substances from their surroundings. Furthermore, the review summarizes that sewage irrigation and atmospheric deposition are significant factors contributing to the co-pollution of heavy metals with MNPs in environmental settings. The interaction between heavy metals and MNPs has been shown to have detrimental effects on agricultural productivity, as it can inhibit crop growth and simultaneously increase the absorption rate of heavy metals in plants. When these contaminated plants enter the food chain, the accumulated heavy metals can ultimately be ingested by humans. This process poses a potential risk for inducing acute coronary syndrome and other CVDs, thereby underscoring the importance of understanding and mitigating the impact of MNPs on human health. In addition, our review also gives examples of the long-term effects of MNPs on cardiovascular function and the adverse consequences such as arrhythmia and atherosclerosis, the limitations of the current studies of MNPs affecting cardiovascular system health and future directions are also explored.

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

Objective:To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) .Methods:This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate.Results:(1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference ( χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences ( P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions:Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Objective:To evaluate the effect of polyetheretherketone (PEEK) periodontal splints and splints made from other materials under static loading on stress distributions in periodontal tissues, cement layer, and splints themselves.Methods:A finite element model based on cone-beam CT imaging data of a 25-year-old male patient (treated at the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University in October 2021 for a cracked maxillary molar) with a healthy and intact mandibular dentition and periodontal health was constructed. The finite element model included anterior mandible dentition, mandibular bone model without bone resorption (WBR group), a periodontally compromised mandible model (control group), and three types of periodontal splints: a PEEK periodontal splint (0.7 mm thick, Young′s modulus: 4.1 MPa), a fiber-reinforced resin (FRC) splint (1.0 mm thick, Young′s modulus: 37.0 MPa), and a titanium splint (1.2 mm thick, Young′s modulus: 110.0 MPa). The bone resorption models fixed with different periodontal splints constituted the experimental groups (PEEK group, FRC group and titanium group). Loading of 100 N was applied on the midpoint of the incisal edge of tooth 41. The direction was set at 0°, which was parallel to the long axis of the tooth and downward. The buccal to lingual and downward angles were 30°and 60°, respectively, perpendicular to the long axis of the tooth and 90° to the lingual side. The finite element analysis software was utilized to analyze the stress distribution characteristics of the periodontal tissues, adhesive layer, and the splint itself in the anterior mandibular teeth among the different group.Results:Under the different loading simulation, in the control group, the maximal von Mises stresses of periodontal ligament and bone were 15.7-50.2 MPa and 38.8-130.3 MPa, respectively, and in the WBR group, the maximal von Mises stresses of periodontal ligament and bone were 3.6-6.4 MPa and 16.5-42.7 MPa, respectively. Under the same loading conditions, the magnitude of maximal von Mises stresses in periodontal tissues in the PEEK group was 4.6-6.2 MPa, and the magnitude of stresses in the periodontal ligament of 41 teeth in the WBR group was similar to that in the PEEK group, but higher than that in the FRC and titanium groups. The maximal von Mises stresses of each group is primarily distributed in the periodontal ligament and alveolar bone at the cervical area of the tooth. The higher the elastic modulus of the splint, the higher its own maximal von Mises stresses, and the smaller the maximal principal stresses transmitted to the adhesive layer. In the PEEK group and titanium group, the stress distribution area in the adhesive layer and the splint was near the splint connection adjacent to tooth 41.Conclusions:Periodontal splints fabricated from three types of materials, are effective in distributing stress within the periodontal tissues of the abutment teeth. Compared to FRC and titanium group, the higher PEEK splint stress value was obtained, and the smaller the stress value was transmitted to its adhesive layer.

Objective To analyze the factors affecting the prognosis of patients with knee osteoarthritis,and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators.Methods The clinical data of 234 pa-tients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed,including 126 males and 108 females;age more than 60 years old for 135 cases,age less than 60 years old for 99 cases.Lysholm knee function score was used to evaluate the prognosis of the patients,and the patients were divided into good progno-sis group for 155 patients and poor prognosis group for 79 patients according to the prognosis.The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors.The patients were divided into experimental co-hort and verification cohort,the results of the multiple factor analysis were visualized to obtain a nomogram prediction model,the receiver operating characteristic curve(ROC),calibration curve and decision curve were used to evaluate the model's dis-crimination,accuracy and clinical benefit rate.Results The results of multivariate analysis showed that smoking,pre-treatment K-L grades of Ⅲto Ⅳ,and high levels of interleukin 6(IL-6)and matrix metallo proteinase-3(MMP-3)were risk factors for the prognosis of patients with knee osteoarthritis.ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95％CI(0.742,0.866)]and 0.786[(95％CI(0.678,0.893)],re-spectively.The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points,respectively.When the threshold probability value in the decision curve was set to 31％,the clinical benefit rates of the experimental cohort and validation cohort were 51％and 56％,respectively.Conclusion The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance,and can provide a reference for taking targeted measures to improve the prognosis of patients.

ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.

Objective To construct a risk prediction model for healthcare-associated infection(HAI)in stroke pa-tients,accurately and effectively screen out potential high-risk groups,and formulate targeted preventive interven-tions to reduce the occurrence of infection.Methods Stroke patients in the"Henan Stroke Cohort"in 2019-2021 were selected as the study objects,and relevant clinical data were collected as the main analysis data for model con-struction and internal validation.The relevant data of stroke patients in three hospitals that had never participated in the cohort construction from January to September 2022 were randomly selected as a test set for external validation of the risk prediction model.The main analysis data were randomly divided into a training set and a test set,and a risk prediction model was constructed based on logistic regression,artificial neural network(ANN)algorithm,extreme gradient boosting algorithm and random forest algorithm,respectively.Multiple indicators were used to evaluate the prediction performance of the model,and the optimal model was externally validated based on the test set data.Results The infection rate of stroke patients was 20.6％in the main analysis data and 56.4％in the test set data.The accuracy of the risk prediction model based on logistic regression was 91.2％,the area under the re-ceiver operating characteristic(ROC)curve(AUC)was 0.938,the precision rate,recall rate,specificity,and the F1 score were 0.851,0.695,0.968,and 0.765,respectively.The accuracy rate,precision rate,specificity and AUC of the logistic risk prediction model and the ANN risk prediction model were all significantly better than other models,while the recall rate and F1 score of the logistic risk prediction model were slightly better than the ANN risk prediction model.The logistic risk prediction model had excellent prediction performance in external validation.Conclusion HAI risk prediction model of stroke patients based on logistic regression can better screen out high-risk stroke patients with infection risk,and can contribute to formulate targeted preventive interventions to reduce the occurrence of infection.

Immmunosuppressants are mainly used to reduce rejection after solid organ transplantation,so as to improve the success rate of organ transplantation.However,long-term use of immunosuppressants can also serious-ly impair the immune function of patients,thereby increasing the risk of viral infection and postoperative complica-tions,leading to transplant failure.Therefore,patients need to use both immunosuppressants and antiviral agents.If some immunosuppressants with antiviral effects are found,the patient's burden of taking medicines will be greatly reduced.Currently,the immunosuppressants with antiviral effect have been focused by researchers.The gradual re-vealing of the antiviral mechanism of these immunosuppressants will help to optimize the treatment plan of postope-rative rehabilitation of organ transplant recipients.Based on the mechanism of rejection of transplanted organ,this paper systematically describes the types of viruses which closely related to infection of organ transplant patients and the molecular mechanism of some immunosuppressants in antiviral aspects,which further provides a new idea for clinical prevention and treatment of viral infection due to organ transplantation.

Objective To design and implement a high-precision ear pulse wave physiological signal detection device for human centrifuge training to solve the problems in measurement and calibration of pilot ear pulse wave signal during human centrifuge training.Methods The high-precision ear pulse wave physiological signal detection device was composed of an ear pulse wave acquisition sensor,a signal acquisition and control unit and a host signal processing module.The ear pulse wave acquisition sensor had an ear-clip-like shape and consisted of an outer shell,an inner shell and an elastic steel plate;the signal acquisition and control unit was made up of an power supply module,a constant voltage module for the light source,a signal acquisition module,a master control module and a data transmission module,which had its software developed with an embedded system;the host signal processing module divided the signal processing into 2 phases of signal pre-processing and pulse wave signal monitoring and display.The detection performance of the device was verified by using a physiological electrical signal calibrator to test the ear pulse wave signals detected with the device;the effectiveness and stability of the device were validated by implementing human centrifuge training experiments with different loads.Results The voltage measurement error,amplitude-frequency characteristics and common mode rejection ratio detected by this device were all within the permitted ranges of JJG 760-2003 Verification Regulation for Electro Cardiac Monitor and JJG 954-2019 Verification Regulation of Digital Electroencephalographs;the device was capable of detecting the ear pulse wave signals of pilot during human centrifuge training in real time with little interference from motion and stable signal quality.Conclusion The device can accurately clarify the changes in the amplitude of the pilot's ear pulse wave during human centrifuge training and effectively reflect the changes in the pilot's cerebral blood flow under positive acceleration.[Chinese Medical Equipment Journal,2024,45(9):35-40]