BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

OBJECTIVE: To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS). METHODS: A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high-throughput sequencing of the 16S rRNA microbial gene. RESULTS: Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-β1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased. CONCLUSION BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.

Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P＜0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P＜0.05 or P＜0.01),while there was no significant difference in the above parameters in the X-NC group(all P＞0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01),and there was no significant difference in all parameters in the X-NC group(all P＞0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.

Objective:To explore the types of pre-diagnosis symptom clusters in patients with acute coronary syndrome (ACS) and identify bridge symptoms between symptom clusters.Methods:From May to October 2023, convenience sampling was used to select 243 ACS patients who visited Shanxi Provincial People's Hospital as participants. The General Information Questionnaire and Chinese version of the McSweeney Acute and Prodromal Myocardial Infarction Symptoms Survey were used for the survey. Exploratory factors were used to analyze symptom clusters, while network analysis was used to identify bridge symptoms between symptom clusters. A total of 243 questionnaires were distributed, and 230 valid questionnaires were collected, with a valid response rate of 94.7% (230/243) .Results:Before diagnosis, ACS patients had four symptom clusters, namely typical chest symptom cluster, typical shoulder and back symptom cluster, fatigue related symptom cluster, and cardiopulmonary symptom cluster. In symptom network analysis, fatigue and anxiety were bridge symptoms between symptom clusters, with fatigue having the highest expected impact coefficient ( rbei=0.387 3), followed by close centrality ( rbc=0.024 2). The bridge mediation ( rbb=35.000) and close centrality ( rbc=0.024 8) of anxiety were the highest. Conclusions:Fatigue and anxiety are bridge symptoms in ACS patients, connecting different symptom clusters. Identifying bridge symptoms is beneficial for improving the efficiency and accuracy of symptom management. Research needs to consider patient heterogeneity and conduct subgroup studies on symptom clusters to further explore the practical significance of core and bridge symptoms in clinical practice.

ObjectiveTo investigate the risk factors for early tumor recurrence after laparoscopic pancreaticoduodenectomy （LPD） in patients with pancreatic ductal adenocarcinoma （PDAC）， and to establish a predictive model. MethodsA retrospective analysis was performed for the clinical data of 240 PDAC patients who underwent LPD in The First Hospital of Jilin University from April 2016 to July 2022， with early postoperative tumor recurrence （time to recurrence ≤12 months） as the study outcome. The patients were randomly divided into training group with 168 patients and validation group with 72 patients at a ratio of 7∶3. In the training group， there were 70 patients （41.67%） with early postoperative recurrence and 98 （58.33%） without early recurrence， and in the validation group， there were 32 （44.44%） with early postoperative recurrence and 40 （55.56%） without early recurrence. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a logistic regression analysis was used to investigate the risk factors for early postoperative recurrence； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to evaluate the discriminatory ability of the model， with AUC>0.75 indicating that the model had adequate discriminatory ability. The Bootstrap resampling method was used for validation after 1 000 times of random sampling， and the model was validated again in the validation group. The calibration curve and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the degree of calibration， and the decision curve analysis was used to evaluate clinical practicability. ResultsThe univariate and multivariate analyses showed that preoperative CA19-9 level≥37 U/mL （odds ratio ［OR］=6.265， 95% confidence interval ［CI］： 1.938‍ ‍—‍ ‍20.249， P<0.05）， maximum tumor diameter >3 cm （OR=10.878， 95%CI： 4.090‍ ‍—‍ ‍28.932， P<0.05）， poor tumor differentiation （OR=3.679， 95%CI： 1.435‍ ‍—‍ ‍9.433， P<0.05）， lymph node metastasis （OR=0.209， 95%CI： 0.080‍ ‍—‍ ‍0.551， P<0.05）， and absence of adjuvant chemotherapy after surgery （OR=0.167， 95%CI： 0.058‍ ‍—‍ ‍0.480， P<0.05）. A nomogram model was constructed based on these factors； the ROC curve analysis showed that the model had an AUC of 0.895 （95%CI： 0.846‍ ‍—‍ ‍0.943， P<0.001）， and the calibration curve and the Hosmer-Lemeshow test showed that the model had a good degree of calibration （P=0.173）. The decision curve analysis showed that the nomogram had a good clinical application value. ConclusionPreoperative CA19-9 level ≥37 U/mL， maximum tumor diameter >3 cm， poor tumor differentiation， lymph node metastasis， and absence of adjuvant chemotherapy after surgery are independent risk factors for the early recurrence of PDAC after LPD， and the nomogram model established based on these factors can effectively predict early postoperative recurrence.

Late-onset circulatory collapse(LCC)in preterm infants is characterized by sudden onset of hypotension and/or oliguria after the first week of life, which is resistant to volume expanders and inotropes but responds rapidly to timely glucocorticoids treatment.LCC should be managed promptly and properly, or it may cause respiratory, digestive complications and life-long neurological problems.Relative adrenal insufficiency is considered the most likely cause of LCC, but its pathophysiology remains unclear.This review summarizes the current reserch about LCC regarding its pathophysiology, clinical features, diagnosis, treatment, and prognosis.

【Objective】 To investigate the intrinsic relationship of social support and psychological capital with college students’ volunteer motivation in the post-epidemic era so as to provide theoretical basis for formulating policies and measures to increase college students’ participation in volunteer activities. 【Methods】 In March 2022, 1 120 college students from 15 universities in Henan Province were selected by convenient sampling method. Their general information, social support, psychological capital, and volunteer motivation were investigated, and univariate analysis, correlation analysis and intermediary effect analysis were performed. 【Results】 The differences of scores in six dimensions of volunteer motivation (i.e., values, understanding, enhancement, career, social interaction, and self-protection) were statistically significant (F=124.90, P<0.001). There were significant differences in social support level of college students of different genders (t=-2.40, P<0.05), and the difference in volunteer motivation level among different grades of college students was statistically significant (F=6.72, P<0.001). Social support, psychological capital, and volunteer motivation were positively correlated with one another (r=0.41, r=0.35, r=0.50, P<0.001). Part of the intermediary effect of psychological capital between social support and volunteer motivation was significant (intermediary effect value=0.49, 95% CI: 0.39-0.59). 【Conclusion】 Colleges and universities can take corresponding measures to improve college students’ volunteer motivation level by improving social support and psychological capital level.

Objective: To examine the effects of obesity and central obesity on hypertension, so as to provide insights into the prevention and control measures of hypertension. Methods: From September to December 2018, residents at ages of 35 to 75 years were sampled using the multi-stage random sampling method in Baiyin District, Baiyin City, Gansu Province, and subjected to questionnaire surveys and physical examinations. The interaction between obesity/central obesity and hypertension was evaluated using logistic regression analysis. The synergy index ( SI ), relative excess risk due to interaction ( RERI ) and attributable proportion due to interaction ( AP ) were calculated using Excel compiled by Andersson et al. Results: A total of 6 246 questionnaires were allocated and 6 169 valid questionnaires were recovered, with an effective recovery rate of 98.77%. The respondents included 3 038 men ( 49.25% ) and 3 131 women (50.75%), with a mean age of ( 52.05±8.78 ) years. There were 832 respondents with obesity ( 13.49% ) and 2 278 with central obesity ( 36.93% ). The crude and standardized prevalence rates of hypertension were 35.89% and 33.05%, respectively. Multivariable logistic regression analysis showed that obesity ( OR=2.020, 95%CI: 1.705-2.393 ) and central obesity ( OR=1.622, 95%CI: 1.433-1.836 ) were statistically associated with hypertension. There was no multiplicative interaction between obesity or central obesity and hypertension ( OR=1.011, 95%CI: 0.655-1.560 ), and no additive interaction was detected between obesity or central obesityand hypertension ( SI=1.405, 95%CI: 0.815-2.424; RERI=0.658, 95%CI: -0.298 to 1.614; AP=0.201, 95%CI: -0.075 to 0.476 ). Conclusions Obesity and central obesity increase the risk of hypertension; however, no interaction is detected between obesity or central obesity and hypertension.

Purpose: This study aimed to identify prognostic factors for patients with distant lymph node-involved gastric cancer (GC) using a machine learning algorithm, a method that offers considerable advantages and new prospects for high-dimensional biomedical data exploration. Materials and Methods: This study employed 79 features of clinical pathology, laboratory tests, and therapeutic details from 289 GC patients whose distant lymphadenopathy was presented as the first episode of recurrence or metastasis. Outcomes were measured as anycause death events and survival months after distant lymph node metastasis. A prediction model was built based on possible outcome predictors using a random survival forest algorithm and confirmed by 5×5 nested cross-validation. The effects of single variables were interpreted using partial dependence plots. A contour plot was used to visually represent survival prediction based on 2 predictive features. Results: The median survival time of patients with GC with distant nodal metastasis was 9.2 months. The optimal model incorporated the prealbumin level and the prothrombin time (PT), and yielded a prediction error of 0.353. The inclusion of other variables resulted in poorer model performance. Patients with higher serum prealbumin levels or shorter PTs had a significantly better prognosis. The predicted one-year survival rate was stratified and illustrated as a contour plot based on the combined effect the prealbumin level and the PT. Conclusions Machine learning is useful for identifying the important determinants of cancer survival using high-dimensional datasets. The prealbumin level and the PT on distant lymph node metastasis are the 2 most crucial factors in predicting the subsequent survival time of advanced GC.Trial Registration: ChiCTR Identifier: ChiCTR1800019978

Purpose: While several prognostic models for the stratification of death risk have been developed for patients with advanced gastric cancer receiving first-line chemotherapy, they have seldom been tested in the Chinese population. This study investigated the performance of these models and identified the optimal tools for Chinese patients. Materials and Methods: Patients diagnosed with metastatic or recurrent gastric adenocarcinoma who received first-line chemotherapy were eligible for inclusion in the validation cohort. Their clinical data and survival outcomes were retrieved and documented. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive ability of the models. Kaplan-Meier curves were plotted for patients in different risk groups divided by 7 published stratification tools. Log-rank tests with pairwise comparisons were used to compare survival differences. Results: The analysis included a total of 346 patients with metastatic or recurrent disease.The median overall survival time was 11.9 months. The patients were different into different risk groups according to the prognostic stratification models, which showed variability in distinguishing mortality risk in these patients. The model proposed by Kim et al. showed relative higher predicting abilities compared to the other models, with the highest χ 2 (25.8) value in log-rank tests across subgroups, and areas under the curve values at 6, 12, and 24 months of 0.65 (95% confidence interval [CI]: 0.59–0.72), 0.60 (0.54–0.65), and 0.63 (0.56–0.69), respectively. Conclusions Among existing prognostic tools, the models constructed by Kim et al., which incorporated performance status score, neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, and tumor differentiation, were more effective in stratifying Chinese patients with gastric cancer receiving first-line chemotherapy.