Objective:To investigate the prevalence of skeletal fluorosis and the management and treatment of patients in endemic fluorosis areas of Shaanxi Province.Methods:From March to November 2023, in accordance with the requirements of the "2023 Monitoring Plan for Endemic Fluorosis in Shaanxi Province", the implementation of prevention and control measures of endemic fluorosis in Shaanxi Province was investigated. The data of patients with skeletal fluorosis from January to December 2023 were downloaded from Shaanxi Province Endemic Disease Control Information Management Platform, and the epidemiological characteristics were analyzed. At the same time, the management and treatment of patients with skeletal fluorosis in endemic fluorosis areas of Shaanxi Province were carried out in accordance with the requirements of the "Shaanxi Province Endemic Disease Patient Management Service Specification".Results:In 2023, there were 10 drinking water-borne endemic fluorosis cities in Shaanxi Province, involving 3 715 endemic villages, including 3 650 water improvement villages with a water-improving rate of 98.25%. There were 2 coal-burning-borne endemic fluorosis cities in Shaanxi Province, involving 641 746 households in 1 414 endemic villages. Among them, 641 617 households had changed their furnaces and stoves, with a furnace and stove change rate of 99.98%. There were 37 462 patients with skeletal fluorosis in the province, with 35 792 from drinking water-borne endemic fluorosis areas and 1 670 from coal-burning-borne endemic fluorosis areas. The condition was mainly mild and moderate (94.12%, 35 258/37 462), with females accounting for 55.13% (20 654/37 462). The education level was mainly primary school and illiteracy (83.64%, 31 333/37 462), and the occupation was mainly farmers (99.29%, 37 196/37 462). A total of 37 116 patients with skeletal fluorosis were followed up and managed, with a management rate of 99.08% (37 116/37 462). A total of 35 756 patients were managed in a standardized manner, and the standardized management rate was 96.34% (35 756/37 116). A total of 30 649 patients with skeletal fluorosis were actually treated, with a treatment rate of 84.27% (30 649/36 370) and a total effective rate of 98.08% (30 062/30 649).Conclusion:In 2023, the prevalence of skeletal fluorosis in endemic fluorosis areas of Shaanxi Province is mainly mild and moderate, with a wide coverage of community management and a high level of treatment efficiency.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

The aim of this study was to investigate the risk factors for brucellar spondylitis.Electronic medical record data for patients with brucellosis at Yidu Central Hospital in Weifang City were retrospectively collected from January 2018 to April 2024,including general data,clinical characteristics,and laboratory examinations.The patients were divided into a spinal in-volvement group and a no spinal involvement group.The risk factors for brucellar spondylitis were determined through multi-factorial logistic regression model analysis.Of the 124 patients with brucellosis,59 had brucellar spondylitis,and 65 had bru-cellosis alone.There were more patients with age ≥55 years(x2=17.71),time from onset to diagnosis ≥30 days(x2=26.17),and low back pain(x2=52.71)in the spinal involvement group than in the group without spinal involvement,and the difference was statistically significant(all P＜0.001);there were more patients with headaches in the group without spinal in-volvement than in the group with spinal involvement,and the difference was statistically significant(x2=8.34,P＜0.05).and there were more patients in the spinal involvement group with neutrophil percent(NEU％)(t=2.94),platelet count(PLT)(t=122.00),blood sedimentation rate(ESR)(Z=-6.74),C-reactive protein(CRP)(Z=-5.74),and interleukin-6(IL-6)(Z=-2.08)were higher in the spine-involved group than in the group without spine-involvement,and the differences were all statistically significant(all P＜0.05);Lactate dehydrogenase was significantly lower in the spine-involved group(LDH)than the group without spinal involvement(t=-2.04,P＜0.042).A multifactorial logistic regression analysis indicated that a du-ration of out-of-hospital symptoms ≥30 days(OR=6.265,95％CI 1.181-33.241),symptoms of low back pain(OR=14.885,95％CI 3.144-70.472),elevated PLT(OR=1.013,95％CI 1.004-1.023),and elevated ESR(OR=1.053,95％CI 1.008-1.100)were risk factors for brucellar spondylitis(all P＜0.05).The optimal cut-off values for ROC analysis were PLT＞278.5 ×109/L(sensitivity 89.2％,specificity 59.3％)and ESR＞16.5 mm/h(sensitivity 69.2％,specificity of 86.4％);using both PLT and ESR for diagnosis yielded an AUROC of 0.891(95％CI 0.831-0.950),a sensitivity of 86.2％,and a specificity of 84.7％.When patients with brucellosis present with symptoms of low back pain,a time from onset to diagnosis of ≥30 days,and markedly elevated ESR and PLT,lumbar magnetic resonance examination is recommended to rule out brucellar spondylitis,to enable early diagnosis and timely treatment,improve patient prognosis,shorten illness duration,and improve patient quality of life.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

Objective To systematically characterizes the temporal changes in urokinase-type plasminogen activator(uPA)over the course of neoplastic progression using a mouse oral squamous cell carcinoma(OSCC)model induced by 4-nitroquinoline-1-oxide(4-NQO).Methods A total of 65 wild-type C57BL/6 mice of 5 weeks old were randomly assigned to two groups,a 4-NQO group(n=50),which received daily administration of 100 μg/mL 4-NQO in drinking water,and a control group(n=15),which received sterile water.At 12,16,20,22,and 24 weeks,10 mice from the 4-NQO group and 3 from the control group were randomly selected,weighed,and sacrificed.Tongue tissues were collected for hematoxylin-eosin(HE)staining to preliminarily assess OSCC development,and for immunofluorescence staining and quantitative real-time PCR to evaluate dynamic uPA expression in tongue tissues during OSCC progression.Results After 16 weeks of exposure,4-NQO-treated mice exhibited significantly lower body mass compared with that of the controls(P<0.05)and the weight loss became increasingly more pronounced over time.Histopathological changes in tongue tissues progressed in a clearly time-dependent manner—hyperplasia and mild dysplasia emerged at week 12,while moderate-to-severe dysplasia and carcinoma were observed by week 22,yielding a tumorigenic rate of 25%,which escalated to 70%by week 24.Immunofluorescence and qPCR analyses demonstrated a pronounced,progressive up-regulation of uPA expression in lesional tissues as OSCC progressed(P<0.000 1).Conclusion This study not only confirmed the uniqueness of the 4-NQO model in OSCC research,but also revealed the changes in uPA during tumor invasion.These findings provide a theoretical foundation for the development of early diagnosis and precision treatment strategies,holding significant potential clinical value and research importance for improving patient prognosis.

Objective To investigate plasma protein expression changes in heatstroke patients using proteomics technology and to identify reliable prognostic biomarkers.Methods A retrospective analysis was conducted on 20 heatstroke patients hospitalized at the 908th Hospital of the Chinese PLA Joint Logistics Support Force from July 2022 to February 2024.Patients were divided into survival(n=16)and death groups(n=4)based on 28-day outcomes.Fasting venous blood samples were collected from both groups for proteomic analysis.Liquid chromatography-mass spectrometry(LC-MS/MS)was used to identify and screen differentially expressed proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed.LASSO regression was applied to screen key prognostic biomarkers,and receiver operating characteristic(ROC)curve analysis was used to evaluate their predictive value.Results A total of 27 upregulated and 90 downregulated proteins were identified between the two groups.These proteins were primarily involved in biological processes such as immune responses,complement activation,and metabolic processes.LASSO regression analysis indicated that actin-related protein 2(ARP2),cysteine-rich scavenger receptor type 1 M130(CD163),and catalase(CAT)could serve as effective biomarkers for evaluating heatstroke prognosis.ROC curve analysis demonstrated that ARP2 had higher diagnostic efficacy(AUC=0.98,sensitivity=0.80,specificity=1.00)compared to CD163(AUC=0.94,sensitivity=0.76,specificity=1.00),CAT(AUC=0.96,sensitivity=0.67,specificity=1.00),and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(AUC=0.79,sensitivity=0.44,specificity=1.00).Conclusion Elevated plasma ARP2 level has good clinical value for predicting poor prognosis in heatstroke patients.

Objective To investigate the effects and mechanisms of ubiquitin-associated domain-containing protein 2(UBAC2)mediated by m6A methylation modification on the invasion and migration abilities of colorectal cancer cells.Methods The GEPIA2.0 database was utilized to analyze the expression differences of UBAC2 mRNA between colorectal cancer tissues and adjacent normal tissues,as well as its expression in colorectal cancer tissues at different stages.The correlation between Wilms tumor 1-associated protein(WTAP)and UBAC2 expression was analyzed.The Kaplan-Meier plotter online tool was applied to analyze the correlation between UBAC2 and the overall survival rate of colorectal cancer patients.The RMVar and SRAMP databases were employed to predict potential m6A methylation modification sites in the UBAC2 gene.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to detect the expression levels of UBAC2 mRNA and protein in colorectal cancer cell lines.For UBAC2 knockdown experiments,SW480 cells were divided into control group(no treatment),sh-NC group(transfected with sh-NC negative control plasmid),and sh-UBAC2 group(transfected with sh-UBAC2 plasmid).For WTAP knockdown experiments,groups included control group(no treatment),si-NC group(transfected with negative control siRNA),and si-WTAP group(transfected with WTAP-targeting siRNA).For UBAC2 overexpression experiments,groups were control group(no treatment),si-WTAP group(transfected with pcDNA3.1 empty plasmid),and si-WTAP+OE-UBAC2 group(transfected with UBAC2 overexpression plasmid pcDNA3.1-UBAC2).Western blotting was used to detect the protein expression levels of UBAC2,WTAP,E-cadherin,N-cadherin,and Vimentin;qRT-PCR was applied to detect the expression level of UBAC2 mRNA;Transwell assays were conducted to assess cell invasion and migration abilities.MeRIP-qPCR was employed to detect the m6A methylation modification of UBAC2 mRNA;RIP-qPCR experiments were conducted to verify the binding of WTAP to UBAC2 mRNA.In nude mouse colorectal cancer lung metastasis experiments,groups included LV-sh-NC group(tail vein injection of SW480 cells stably infected with LV-sh-NC)and LV-sh-UBAC2 group(tail vein injection of SW480 cells stably infected with LV-sh-UBAC2).After 42 d of tumor-implantation in nude mice,lung tissues were harvested:the number of lung nodules observed by hematoxylin/eosin(HE)staining,and the expression level of Luc2 mRNA detected by qRT-PCR.Results GEPIA2.0 database analysis revealed that the expression level of UBAC2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent normal tissues,and it gradually increased with the progression of tumor stage(P<0.05).The expression levels of UBAC2 mRNA and protein in multiple colorectal cancer cell lines were significantly higher than those in normal colonic epithelial cells(P<0.05).Compared with sh-NC group,sh-UBAC2 group showed significantly increased E-cadherin protein expression,significantly decreased N-cadherin and Vimentin protein expression,and significantly reduced number of invaded and migrated SW480 cells(P<0.05).GEPIA2.0 database analysis results indicated a positive correlation between WTAP and UBAC2 expression(r=0.24,P<0.001).Compared with si-NC group,si-WTAP group showed significantly decreased expression levels of WTAP and UBAC2 mRNA and protein in SW480 cells(P<0.05).MeRIP-qPCR results demonstrated that the m6A modification level of UBAC2 mRNA in si-WTAP group was significantly lower than that in si-NC group(P<0.05).RIP-qPCR further confirmed that WTAP could bind to UBAC2 mRNA.Compared with control group,si-WTAP group showed significantly increased E-cadherin protein expression and significantly decreased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05);compared with si-WTAP group,si-WTAP+OE-UBAC2 group showed significantly decreased E-cadherin protein expression and significantly increased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05).The number of lung nodules in LV-sh-UBAC2 group was significantly fewer than that in LV-sh-NC group,and the expression level of Luc2 mRNA in lung tissues was significantly lower than that in LV-sh-NC group(P<0.05).Conclusion UBAC2 mediated by m6A methylation modification can regulate the epithelial-mesenchymal transition(EMT)process in colorectal cancer cells,thereby affecting the invasion and migration abilities of colorectal cancer cells.

Objective:To compare the effects of propofol and dexmedetomidine for sedation on the outcome in mechanically ventilated patients with severe pulmonary infection.Methods:Patients with severe pulmonary infection (Clinical Pulmonary Infection Score >7) requiring mechanical ventilation from the Medical Information Mart for Intensive Care Ⅳ database between 2008 and 2020 were selected and divided into propofol group and dexmedetomidine group based on the sedative agent used. The primary outcome was all-cause in-hospital mortality, and secondary outcomes included 90-day all-cause mortality and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders, and logistic regression and linear regression were applied to analyze the effects of the two sedative drugs on the outcomes of mechanically ventilated patients with pulmonary infection. Kaplan-Meier survival curves were used to analyze survival outcomes.Results:A total of 6 204 critically ill patients with pulmonary infection requiring mechanical ventilation were included, with 3 439 cases in propofol group and 2 765 cases in dexmedetomidine group. The baseline characteristics between the two groups were well balanced (standardized mean difference < 0.1) after IPTW adjustment. In the IPTW-adjusted cohort, the in-hospital all-cause mortality and 90-day all-cause mortality were significantly lower in dexmedetomidine group than in propofol group (439.2[18.7%] vs 563.6[24.1%], 618.0[26.3%] vs 733.6[31.3%], P<0.001), the results of Further Kaplan-Meier survival curve analysis showed that the 90-day all-cause mortality was significantly lower in dexmedetomidine group than in propofol group ( P<0.01). Conclusions:Compared with propofol, dexmedetomidine can decrease the mortality rate and improve the prognosis in mechanically ventilated patients with severe pulmonary infection when used for sedation.