BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

BACKGROUND:Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+overload,but the mechanism of Ca2+flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear.OBJECTIVE:To investigate the effect of fluoride exposure on Ca2+transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.METHODS:Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7.The nerve cells were divided into control group(containing 0 mmol/L sodium fluoride),low fluoride group(containing 0.5 mmol/L sodium fluoride),and high fluoride group(containing 1 mmol/L sodium fluoride).The cell morphological changes were observed by light microscope 24 hours after fluorine exposure.The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1,GRP 75,and IP3R were detected using western blot assay.The expression levels of VDAC1,GRP 75,and IP3R mRNA were detected by RT-PCR.Ca2+levels were detected by Rhood-2AM Ca2+probe.Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential.The level of apoptosis was determined by flow cytometry and TUNEL staining.RESULTS AND CONCLUSION:(1)The purity of neurons cultured on day 7 had been determined to be over 90％,with few impurities,good growth status,and tight cell network connections,meeting the requirements of subsequent experiments.(2)Compared with the control group,growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased;the processes were broken;the cell body was rounded,and the connection network between cells was destroyed.Compared with the low-fluoride group,the cell damage changes in the high-fluoride group were more obvious.(3)Compared with the control group,the protein expressions of VDAC1,GRP75,and IP3R were increased in the low-fluoride group and the high-fluoride group(P＜0.05),and the ratio of apoptosis-related protein BAX/BCL-2 was increased(P＜0.05).Compared with the control group,the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased(P＜0.05);the expression levels of VDAC1,GRP75,and IP3R mRNA in the high-fluoride group were significantly increased(P＜0.01).(4)The level of cell apoptosis increased significantly after fluoride exposure,and the high-fluoride group was significantly higher than the control and low-fluoride groups(P＜0.01).(5)After fluoride exposure,the concentration of mitochondrial Ca2+in nerve cells increased significantly(P＜0.05),the mitochondrial membrane potential decreased(P＜0.01),and the degree of damage in the high-fluoride group was more obvious(P＜0.05).The results show that fluoride exposure impairs the morphological structure of primary neural cells,resulting in upregulation of Ca2+transfer pathway protein expression between the endoplasmic reticulum and mitochondria,mitochondrial Ca2+overload,mitochondrial damage,and increased levels of apoptosis.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.

Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

Objective To systematically evaluate the predictive models for re-admission in patients with heart failure (HF) in China. Methods Studies related to the risk prediction model for HF patient re-admission published in The Cochrane Library, PubMed, EMbase, CNKI, and other databases were searched from their inception to April 30, 2024. The prediction model risk of bias assessment tool was used to assess the risk of bias and applicability of the included literature, relevant data were extracted to evaluate the model quality. Results Nineteen studies were included, involving a total of 38 predictive models for HF patient re-admission. Comorbidities such as diabetes, N-terminal pro B-type natriuretic peptide/brain natriuretic peptide, chronic renal insufficiency, left ventricular ejection fraction, New York Heart Association cardiac function classification, and medication adherence were identified as primary predictors. The area under the receiver operating characteristic curve ranged from 0.547 to 0.962. Thirteen studies conducted internal validation, one study conducted external validation, and five studies performed both internal and external validation. Seventeen studies evaluated model calibration, while five studies assessed clinical feasibility. The presentation of the models was primarily in the form of nomograms. All studies had a high overall risk of bias. Conclusion Most predictive models for HF patient re-admission in China demonstrate good discrimination and calibration. However, the overall research quality is suboptimal. There is a need to externally validate and calibrate existing models and develop more stable and clinically applicable predictive models to assess the risk of HF patient re-admission and identify relevant patients for early intervention.

Objective: To analyze the association between dietary diversity and cognitive function among the elderly using group-based trajectory model, so as to provide the basis for formulating dietary intervention strategies to prevent cognitive impairment. Methods: Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) project, demographic information, lifestyle behaviors, psychological well-being, and activities of daily living of elderly individuals aged ≥65 years from 2008 to 2018 were collected. Dietary diversity was assessed using a food frequency questionnaire, with a score of <7 points defined as low dietary diversity. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). A group-based trajectory model was established based on cognitive function scores from 2008 to 2018 to analyze the trajectories of cognitive function change. The association between dietary diversity and cognitive function was analyzed using a multinomial logistic regression model. Results: A total of 1 613 individuals were collected, with a median age was 72.00 (interquartile range, 10.00) years. There were 810 males (50.22%) and 803 females (49.78%). The group-based trajectory model analysis categorized the participants into three groups: the low-level normal group, the high-level normal group, and the slow-then-rapid decline group, comprising 796 (49.35%), 585 (36.27%), and 232 (14.38%) individuals, respectively. Among these groups, the numbers of individuals with low dietary diversity were 497 (62.44%), 311 (53.16%), and 166 (71.55%), respectively, with a statistically significant difference (P<0.05). Multinomial logistic regression analysis showed that after adjusting for demographic information, lifestyle behaviors, psychological well-being, and activities of daily living, compared with the high-level normal group, low dietary diversity was statistically associated with cognitive function in the slow-then-rapid decline group (OR=1.622, 95%CI: 1.103-2.384). Conclusion Low dietary diversity may increase the risk of cognitive impairment among the elderly.

Objective The aim of this study was to characterize the basic molecular and biochemical parameters for a cyclophilin protein in Cryptosporidium parvum called CpCyP1.Methods CpCyP1 expression patterns during the parasite life cycle were evaluated using qRT-PCR with total RNA isolated from different developmental stages of C.parvum.Native CpCyP1 protein in sporozoites was detected using western blot.The localization of CpCyP1 was performed using the immunofluorescence assay,with an affinity-purified rabbit polyclonal antibody against a synthetic peptide.The peptidyl-prolyl cis-trans isomerase(PPIase)activity of His-tagged recombinant CpCyP1 was evaluated using absorbance colorimetry,and the effect of cyclosporin A(CsA)on the activity of CpCyP1 was determined.Results CpCyP1 was expressed in all parasite developmental stages,whereas CpCyP1 was present mainly in the cytosol of sporozoites,meronts,and gamonts.CpCyP1 displayed Michaelis-Menten kinetics towards N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide for its PPIase activity(Km=456.4 μmol/L;Vmax=1.981 U).CsA inhibited PPIase activity,showing lower micromolar inhibitory activity and binding affinity(Kd=5.122 μmol/L;IC50=1.004 μmol/L).Conclusions These results imply that CpCyP1 in the parasite may be the target for the previously reported anti-cryptosporidial efficacy of CsA and suggest that C.parvum cyclophilins could be evaluated as candidate drug targets.

Objective To explore the mediating effect of psychological resilience between perceived spousal support and dignity loss in breast cancer patients.Methods A convenience sampling method was employed,involving 377 breast cancer patients who met the study criteria and received treatment at a tertiary oncology hospital in Yunnan Province from March to September 2023.Data were collected using a general information questionnaire,the Dignity Scale,the Perceived Spousal Support Scale,and the Psychological Resilience Scale.Data analysis was conducted using IBM SPSS 26.0 software.Results The scores for dignity loss,perceived spousal support,and psychological resilience of breast cancer patients were(41.72±6.77),(100.42±6.93),and(75.27±8.50),respectively.Pearson correlation analysis showed that dignity loss was negatively correlated with both perceived spousal support and psychological resilience(r1=-0.568,r2=-0.640,both P＜0.05).Mediation effect analysis indicated that psychological resilience had a mediating effect between perceived spousal support and dignity loss,with a value of-0.320(95％CI-0.409 to-0.246),accounting for 57.1％of the total effect.Conclusion The dignity of breast cancer patients in this study is in a state of mild loss,and psychological resilience plays a partial mediating role between perceived spousal support and dignity loss.This suggests that clinical medical staff should pay attention to the spousal support situation of breast cancer patients,provide timely guidance and health education to spouses,enhance the level of support from spouses,and strengthen the confidence and capability of couples in jointly coping with the disease,thereby alleviating dignity loss in breast cancer patients and improving their quality of life.

Objective To systematically evaluate the incidence and influencing factors of falls in adult cancer patients,and provide evidence support for early identification and prevention of falls.Methods Eight Chinese and English databases,including PubMed,Embase,CNKI,and Wanfang Database,were searched by computer.The databases were established until January 2024 and included in cross-sectional,cohort,and case-control studies based on the incidence and/or influencing factors of falls in adult cancer patients.Two researchers independently screened and reviewed literature,evaluated literature quality,and extracted data before conducting meta-analysis using RevMan 5.4 software.Results A total of 19 articles were incorporated into the research,with a total sample population size of 70508 cases.The results showed that the incidence of comorbid falls in adult tumor patients was 23.0%(95%CI 0.23,0.24).Age,female,low education level,fall history,fall fear,middle and late stage of tumor,tumor type(breast cancer,reproductive system tumor,prostate cancer),comorbidity,chemotherapy,radiotherapy,multiple drugs(n≥5),drugs(antidepressants,antipsychotics,sedatives and hypnotics),related symptoms(fever,peripheral neuropathy,fatigue,depression),malnutrition,low weight,cognitive dysfunction,balance disorders,gait abnormalities,and low ability of daily living were the influencing factors for falls of adult tumor patients.Conclusion Cancer professionals should identify the influencing factors of falls early and take targeted measures to reduce the occurrence of falls.