Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

This paper explores the intersection and integration of narrative medicine and clinical spiritual care,especially the importance and value of spiritual narrative in medical services.Spiritual narrative is based on the three elements of narrative medicine,combined with the professional competence of clinical spiritual care,to achieve multi-angle attention to patients'physiology,psychology,society,and spirit.The connections and situations between individuals in the disease story are reproduced in the spiritual narrative,allowing the narrator to deeply understand the relationship between themselves,others,and natural events from a more diverse perspective,thereby enhancing the role identity and professional happiness of doctors,and ultimately promoting the narrator's exploration of their own inner selves and understanding of life philosophy.Integrating narrative medicine into undergraduate teaching,research,and clinical practice of the clinical spiritual care program at Hunan Cancer Hospital,conducting spiritual narrative,is of great significance for improving the empathy and communication skills of medical students and clinical medical staff,promoting their thinking and understanding of the meaning of life,and enhancing their patient-centered clinical critical thinking ability.

The presence of food-borne pathogenic bacteria poses a severe threat to human health. Therefore,it is essential to develop effective methods for bacteria detection. Herein,a method based on digital polymerase chain reaction (PCR) chip was developed for rapid and effective detection of three kinds of common food-borne bacteria (Staphylococcus aureus,Salmonella typhimurium and Listeria monocytogenes). Driven by centrifugal force,samples could be easily loaded and digitized in 15 min. PCR results showed that the positive microchambers in the chip could be identified after 25 thermal cycles. The chip had advantages in the quantitative detection of bacterial nucleic acid at low concentration,which could effectively avoid false negative results. Multiple detection of bacterial samples with concentration of 105-108 CFU/mL could also be realized using this chip. Compared with fluorescent quantitative PCR,this method had higher accuracy and sensitivity,especially for detection of targets at low concentration.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective To preliminarily explore the correlation between traditional Chinese Medicine(TCM)syndrome types of patients with polycystic ovary syndrome(PCOS)and their lifestyle and emotional factors such as diet,sleep and exercise,thus to provide more information for guiding the treatment and lifestyle correction for patients with PCOS.Methods A questionnaire survey was conducted in 234 patients who were diagnosed with PCOS and meet the inclusion and exclusion criteria of the study at Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,from January 2020 to February 2023.The collection of relevant information covered general information,diet,sleep,exercise,and psychological state.And then the patients were differentiated as four TCM syndrome types,namely spleen deficiency and phlegm-damp type,kidney deficiency and liver constraint type,kidney deficiency and blood stasis type,phlegm blended with blood stasis type according to the symptoms as well as tongue manifestation and pulse condition.The distribution of the TCM syndrome types in PCOS was investigated,and the lifestyle factors of general information,diet,sleep,exercise,and emotions in PCOS patients with various TCM syndrome types were analyzed by statistical methods,aiming to explore the relationship between the lifestyle factors and TCM syndrome types.Results(1)The analysis of the distribution of TCM syndrome types showed that among the 234 PCOS patients,104 cases(accounted for 44.4%)were differentiated as spleen deficiency and phlegm-damp type,which was the predominant type,and then came kidney deficiency and liver constraint type(85 cases,accounting for 36.3%),phlegm blended with blood stasis type(28 cases,accounting for 12.0%),and kidney deficiency and blood stasis type(17 cases,accounting for 7.3%)in descending order.(2)The correlation of TCM syndrome types with lifestyle factors such as diet,sleep and exercise and emotional factors showed that statistically significant differences were presented in the body mass index(BMI),dietary preference,five-flavor preference,having or not having exercise habits,exercise frequency,duration of exercise,exercise mode,exercise intensity,time from going to bed to falling asleep,duration of sleep,emotions being or not being calm,presence of anxiety or not,and presence of impatience and irritability or not in PCOS patients with various TCM syndrome types(P＜0.05 or P＜0.01).However,there were no statistically significant differences in the age,education level,occupation,family history,history of weight loss,dietary condition,sleep quality,time to fall asleep,frequency of staying up late,depression,obsessive-compulsive disorder,forgetfulness,fatigue,and self-consciousness of high pressure from work and study in PCOS patients with various TCM syndrome types(P＞0.05).Conclusion Healthy lifestyle is of great practical significance for the prevention and treatment of PCOS.The investigation of the correlation of TCM syndrome types with diet,sleep,exercise and psychological state of PCOS patients reveals the possible risk factors for TCM syndromes in PCOS,which will enable the practitioners to perform targeted lifestyle correction for PCOS patients with different TCM syndrome types,and has positive significance for targeted diagnosis and treatment of PCOS patients with different TCM syndrome types.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective:To investigate the clinical effect of Alirocumab in reducing low density lipoprotein cholesterol(LDL-C)in patients with coronary heart disease(CHD)and substandard blood lipids and its effect on atheroscle-rotic plaque.Methods:A total of 127 CHD patients with substandard blood lipids who were treated in Shenzhen Longhua District People's Hospital between September 2017 and March 2021 were selected.According to patients re-ceived Alirocumab therapy or not,they were divided into control group(n=81)and combined group(n=46).The control group remained original statin therapeutic regimen,while combined group received additional PCSK9 inhibi-tor Alirocumab injection based on original statin therapeutic regimen,75mg subcutaneously,once every 2 weeks.Both groups were treated for 3 months,then followed up for 12 months.Levels of total cholesterol(TC)and LDL-C,plaque fiber cap thickness,lipid plaque radian,lipid plaque length and minimum lumen cross-sectional area before and after 12-month follow-up,and incidence of adverse reactions and clinical endpoint events were com-pared between two groups.Results:After 12-month follow-up,compared with control group,combined group had significant lower plasma levels of TC[(3.48±1.04)mmol/L vs.(2.29±0.76)mmol/L],LDL-C[(2.08±0.53)mmol/L vs.(1.27±0.41)mmol/L],lipid plaque radian[(107.22±13.29)° vs.(92.65±11.81)°]and lipid plaque length[(5.45±0.89)mm vs.(4.84±0.82)mm],and significant higher plaque fiber cap thickness[(123.60±14.87)μm vs.(131.46±14.29)μm]and minimum lumen cross-sectional area[(2.51±0.37)mm2 vs.(2.69±0.33)mm2](P＜0.01 all).There was no significant difference in incidence rates of adverse reactions(x2=0.428,P=0.513)and clinical endpoint events(x2=0.253,P=0.615)between two groups.Conclusion:Alirocumab can significantly reduce LDL-C level,increase the plaque fiber cap thickness and lumen cross-section-al area,reduce the internal lipid load of plaque and improve the stability of plaque with good safety in CHD patients with substandard blood lipids.

Objective:To investigate the relative expression level and clinical significance of LINC00475 in serum of patients with multiple myeloma(MM).Methods:The expression of LINC00475 in serum of 108 MM patients and five MM cell lines including RPMI 8226,NCI-H929,U266,OPM2 and CAG were detected by real-time fluorescence quantitative PCR.The diagnostic value of LINC00475 in MM was evaluated by receiver operating characteristic(ROC)curve analysis.The correlation of LINC00475 with patients'characteristics was analyzed.Results:Compared with control groups,the expression of LINC00475 was up-regulated in serum of MM patients and MM cell lines(all P＜0.05).ROC curve analysis showed that the optimal cut-off value of LINC00475 was 262.4,the area under curve(AUC)was 0.924(95％CI:0.884-0.964),and sensitivity and specificity was 83.3％and 91.7％,respectively,which indicated that LINC00475 had good evaluation value in MM patients.Compared with low-LINC00475 expression group,patients in high-LINC00475 expression group had higher levels of β2-microglobulin(β2-MG)and Cystatin C(Cys-C)but lower albumin(ALB)(all P＜0.05).Compared with MM patients with International Staging System(ISS)stage I,the expression level of LINC00475 was significantly higher in patients with stage Ⅱ and Ⅲ(both P＜0.05).Conclusion:LINC00475 is helpful to distinguish MM patients from healthy adults,which is correlated with the prognostic indicators such as β2-MG,ALB,and ISS stage.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.