Objective To investigate the impact of Sca-1 bone marrow derived stem cells on apoptosis in murine cardiac fibroblasts and the molecular mechanisms of young(Y)Sca-1 bone marrow stem cell(BMSC)on old(O)cardiac fibroblast cell(CFC)apoptosis.Methods The apoptosis and survival of Y and O CFC were assessed under hypoxic conditions.Co-cultures of Y and O Sca-1 bone marrow-derived mesenchymal stem cells(BMSC)with O CFC were established to investigate the impact of Sca-1 BMSC on the apoptotic response and viability of O CFC,employing TUNEL staining,qRT-PCR,Western Blot,and CCK8 assays.Furthermore,differential secretion profiles of growth factors by Y and O Sca-1 BMSC were compared using qRT-PCR and ELISA analysis.Results Compared to Y CFC,O CFC exhibited an increased rate of apoptosis and a decreased rate of cell survival.However,when compared to O cells,Y Sca-1 BMC significantly reduced apoptosis in O CFC and enhanced cell survival.Moreover,Y Sca-1 BMSC demonstrated a higher secretion of GDF5(Growth Differentiation Factor 5)than O cells(P<0.05).Importantly,the protective effects of Y Sca-1 BMSC on apoptosis and survival in O CFC were abolished upon neutral-ization of GDF5 expression.Conclusion Y Sca-1 BMSC decreases O CFC apoptosis through GDF5.

Objective To explore the selection rules of acupuncture and moxibustion for treating ovarian dysfunction-related diseases by applying data mining technology.Methods Computer searches were conducted to find clinical research literature on acupuncture and moxibustion for ovarian reserve dysfunction-related diseases(including diminished ovarian reserve,premature ovarian insufficiency,premature ovarian failure)in major databases,such as China National Knowledge Infrustructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and China Science and Technology Journal Database(VIP),Excel 2021 was used to establish a prescription database of acupoints selection,and SPSS Modeler 18.0 and SPSS Stastics 26.0 software were used to analyse the frequency,meridian tropism,site,special acupoints,analysis of association rule,and cluster analysis of acupoints to study the rules of acupuncture and moxibustion for treating ovarian reserve dysfunction-related diseases.Results A total of 215 articles were screened to meet the requirements,in which,96 acupoints were used,with a total frequency of 2 110 times.The high-frequency used acupoints were Guanyuan(RN4),Sanyinjiao(SP6),and Shenshu(BL23),etc,.The commonly used meridians were the conception vessel(CV)and bladder meridian of foot-taiyang,and the acupoints were mostly located in the abdomen and lower limbs,with the majority being the five-shu point and the yuan front-mu points.The core acupoints and four effective clusters were analysed.Conclusion The acupoint selection of acupuncture and moxibustion for ovarian reserve dysfunction-related diseases focuses on tonifying qi and blood,cultivating the vital essence and tonifying the kidneys.Most of the meridians related to reproduction were selected in this method,which aiming at regulating menstruation and tonifying blood,and pre-cultivating its loss.This research focuses on the matching of neighboring point and distant point selection,and pays attention to the use of specific acupoints,and treates multiple organs simultaneously.

This study investigated the prevalence of Borrelia burgdorferi,Anaplasma phagocy tophilum,Rickettsia typhi,Orientia tsutsugamushi,Leptospira interrogans,Francisella tularensis,and Babesia spp.in small mammals in the Qinghai plateau region,to provide a scientific basis for the prevention and control of local zoonotic diseases.Small mammals were cap-tured with snap traps at six sampling sites in the Qinghai plateau region.Liver,spleen,and kidney tissues were collected for detection of six bacterial pathogens with real-time PCR.Conventional PCR(cPCR)was used for Babesia detection,and the positive PCR products were sequenced and analyzed.The differences in pathogen detection rates among species and habitats were analyzed with x2 test or Fisher's exact test.In to-tal,235 small mammals from 15 species were captured.B.burgdorferi,L.interrogans,and Babesia were detected in 11 spe-cies of small mammals,whereas A.phagocytophilum,R.typhi,O.tsutsugamushi,and F.tularensis were not detected.B.burgdorferi was detected in 41 small mammals from nine species(Cricetulus longicaudatus,Apodemus peninsulae,Ochotona curzoniae,Mus m usc ulus,Meriones meridians,Microtus arvalis,Cricetidae,Ochotona cansus,and Allactaga sibirica),with an infection rate of 17.45％(41/235).L.interrogans was detected in eight small mammals from four species(C.longicaudatus,M.musculus,M.arvalis,and Microtus oeconomus),with an infection rate of 3.40％(8/235).Babesia was detected in only one Mustela altaica,with an infection rate of 0.85％(1/235).Statistically significant differences were ob-served in the detection rates of pathogens among small mammal species(x2=200.54,P＜0.05).Among habitats,the detection rate of B.burgdorferi was highest in the forest(Fisher's exact test,P＜0.05).B.burgdorferi and L.interrogans co-infection was observed in three M.arvalis and two C.longicaudatus.In addition,one Babesia sequence was obtained,which clustered with Babesia vulpes in the phylogenetic tree.B.burgdorferi,L.interrogans,and Babesia were the main pathogens prevalent in small mammals in the Qinghai plateau region and have potential to cause human diseases.Local authori-ties should strengthen the surveillance of corresponding zoonotic diseases,and formulate corresponding prevention and control measures.

Abstract: Objective To explore the risk factors for macrolide unresponsive mycoplasma pneumoniae pneumonia (MUMPP) in children and to develop a model for predicting the risk of MUMPP. Methods Children with mycoplasma pneumoniae pneumonia admitted to the Pediatric Department of Leshan People's Hospital who met the inclusion criteria from March 1, 2023, to December 1, 2023, were retrospectively selected and divided into the responsive group and unresponsive group according to their reactions to macrolides. General patient data, laboratory tests, and imaging findings were collected and compared. Logistic regression analysis was used to analyze the risk factors of the Macrolide unresponsive mycoplasma pneumoniae pneumonia, and R language (R4.2.3) to establish the nomogram model. The goodness of fit, discriminative ability, calibration, and clinical utility of the model were assessed using the Hosmer-Lemeshow goodness of fit test, receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. Results A total of 224 patients were included in the analysis of children. Among them, 156 (70%) were randomly selected as the training set, and the remaining 68 cases (30%) were used as the validation set. Logistic regression analysis revealed that pleural effusion (OR=6.986, 95%CI 1.362-35.847), highest temperature before admission (OR=3.095, 95%CI 1.487-6.439), neutrophil count (OR=1.294, 95%CI:1.103-1.519), C-reactive protein (OR=1.030, 95%CI 1.002-1.058), and procalcitonin (OR=2.899, 95%CI:1.353-6.214) were independent risk factors for MUMPP in children (all P<0.05). A nomogram was established using R software. The Hosmer-Lemeshow goodness of fit tests for the training set and the validation set were χ2=4.018 and χ2=4.657 (all P>0.05), indicating a good fit of the model. The AUC values for the training set and validation were 0.825 (95%CI: 0.755-0.894) and 0.828 (95%CI 0.729-0.928), respectively, suggesting good discriminative ability of the model. Calibration curve analysis suggested that the model had good predictive performance, while decision curve analysis indicated a high clinical application value of the predictive model. Conclusions Pleural effusion, highest body temperature before admission, neutrophil count, C-reactive protein, and procalcitonin are independent risk factors for MUMPP in children. The prediction model constructed based on the above variables has high predictive efficacy and clinical application value.

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.
Male ; Female ; Humans ; Risk Factors ; Diabetes Mellitus/epidemiology* ; Mortality, Premature ; Smoking ; Cost of Illness ; China/epidemiology* ; Global Burden of Disease

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L

This study explored the usefulness of two-dimensional shear wave elastography (2D-SWE) in the early assessment of corpora cavernosa fibrosis (CCF). New Zealand male rabbits were randomly assigned to an experimental group or a control group. Recombinant human transforming growth factor beta 1 (TGF-β1) was injected into the dorsal penis tissue of rabbits in the experimental group. Conventional ultrasound and 2D-SWE examinations were performed before and 20 days after injection. Penile histological analysis was performed by hematoxylin-eosin staining, sirius red staining, and immunohistochemistry. Measurement of 2D-SWE examination results was performed using shear wave elastography quantitative measurement (SWQ). Histological analysis outcomes were the proportion of smooth muscle cells (SMCs), collagen fibers (CFs), collagen type I (Col I), and collagen type III (Col III), as well as the SMCs/CFs ratio, measured by sirius red staining. Other histological analysis outcomes were the positive area proportion (PAP) of TGF-β1 (PAP_T), fibronectin (PAP_F), and Col III (PAP_C), measured by immunohistochemistry. After recombinant human TGF-β1 injection, SWQ was higher in the experimental group than that in the control group (P < 0.001); however, there were no differences in conventional ultrasound results. There were significant differences in histological outcomes between the two groups (all P < 0.05). These results indicated that 2D-SWE was superior for identifying early histological changes in CCF.
Animals ; Elasticity Imaging Techniques/methods* ; Fibrosis ; Male ; Penis/pathology* ; Rabbits ; Transforming Growth Factor beta1/metabolism*