Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

OBJECTIVE To investigate the correlation between serum levels of asprosin and adropin in elderly patients with obstructive sleep apnea syndrome(OSAS)and the disease severity.METHODS From August 2021 to August 2023,131 elderly OSAS patients admitted to Ezhou Central Hospital were collected as observation subjects(OSAS group),according to the sleep apnea hypopnea index(AHI),there were 40 cases in the mild group,52 cases in the moderate group,and 39 cases in the severe group,meantime,124 healthy individuals who came to health clinic of our hospital for physical examination were collected as the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to determine the levels of asprosin and apropin in the serum of OSAS patients;Pearson method was applied to analyze the correlation between serum asprosin,apropin levels and AHI,ODI,and LSaO2.ROC curve was used to analyze the diagnostic value of serum asprosin and adropin levels in OSAS and the severity of OSAS patients.RESULTS Compared with the control group,the asprosin level in the OSAS group was obviously increased,while the adropin level was obviously reduced(P<0.05).There was no statistically obvious difference in gender,age,coronary heart disease,hypertension,TC,TG,HDL-C,LDL-C among the mild,moderate,and severe groups(P>0.05);compared with the mild group,the levels of BMI,AHI,ODI,and asprosin in the moderate and severe groups were obviously increased,while the levels of LSaO2 and apropin were obviously reduced(P<0.05);compared with the moderate group,the levels of BMI,AHI,ODI,and asprosin in the severe group were obviously increased,while the levels of LSaO2 and apropin were obviously reduced(P<0.05).The serum asprosin level in OSAS patients was positively correlated with AHI and ODI,and negatively correlated with LSaO2(P<0.05);the level of apropin was negatively correlated with AHI and ODI,and positively correlated with LSaO2(P<0.05).The AUC of serum asprosin,apropin levels,and their combination in diagnosing moderate and severe OSAS was 0.832,0.882,and 0.942,respectively,the combined diagnostic value of the two was superior to that of single diagnosis(Z=3.435,2.560,P=0.001,0.011).Serum asprosin,adropin levels and AUC of combined diagnosis of OSAS were 0.818,0.804 and 0.893,respectively.The value of combined diagnosis was better than that of single diagnosis(Z=3.886,4.126,P=0.000,0.000).CONCLUSION The serum level of asprosin is increased and the level of adropin is decreased in patients with OSAS,which is closely related to the severity of the disease,and may be used in the clinical diagnosis of OSAS and the evaluation of the severity of OSAS.

Objective To explore the value of expression levels of serum thioredoxin-interacting protein(TXNIP)and baculoviral IAP repeat-containing protein 5(BIRC5)in clinical staging and efficacy monitoring in patients with primary laryngeal cancer(PLC).Methods From June 2020 to January 2023,a total of 68 pa-tients with PLC accepted by the hospital were collected as PLC group,and 80 patients with benign lesions were set as the benign tumors group.After six months of treatment,patients in the PLC group were separated into the treatment effective group(50 cases)and the treatment ineffective group(18 cases)according to the RECIST solid tumor efficacy evaluation criteria.Enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of TXNIP and BIRC5 in serum of each group;the diagnostic efficacy of TXNIP and BIRC5 in staging PLC and the predictive efficacy of PLC patients were analyzed using the receiver operating characteris-tic(ROC)curve.Results There were statistically significant differences in the expression levels of TXNIP and BIRC5 in the serum between the PLC group and the benign tumors group(P＜0.05).The level of serum TXNIP in the treatment effective group[(99.52±14.12)pg/mL]was obviously higher than that in the treat-ment ineffective group[(85.19±15.17)μg/mL],and the difference was statistically significant(t=3.621,P＜0.05),while the BIRC5 expression level[(15.26±3.65)pg/mL]was obviously lower than that in the treatment ineffective group[(19.13±3.74)pg/mL],and the difference was statistically significant(t=3.833,P＜0.05).The serum TXNIP expression level in early PLC patients[(101.39±12.85)pg/mL]was obviously higher than that in late stage patients[(91.27±13.36)μg/mL],and the difference was statistically significant(t=3.154,P＜0.05),while the BIRC5 expression level[(14.43±3.07)pg/mL]was obviously lower than that in late stage patients[(17.74±3.04)pg/mL],and the difference was statistically significant(t=4.439,P＜0.05).The area under the curve(AUC)of serum TXNIP and BIRC5 in diagnosing PLC stag-ing was 0.829(95％CI:0.718-0.909)and 0.795(95％CI:0.679-0.883),respectively,with sensitivity of 81.58％and 89.47％,and the AUC of TXNIP combined BIRC5 in diagnosing PLC staging was 0.899(95％CI:0.802-0.959),with sensitivity of 94.74％.The AUC of serum TXNIP and BIRC5 in predicting the effi-cacy of PLC patients was 0.818(95％CI:0.705-0.901)and 0.761(95％CI:0.642-0.856),respectively,the AUC of the combination of the two was 0.921(95％CI:0.830-0.973),which had higher predictive efficiency(P＜0.05).Conclusion TXNIP is lowly expressed in the serum of patients with PLC,while BIRC5 is highly expressed in the serum of patients with PLC.The combination detection of TXNIP and BIRC5 has certain effi-cacy in the diagnosis of PLC staging and predicting the efficacy of PLC patients.

Objective To investigate the effect of leflunomide(LEF)on the expression of associated autophagy genes in synoviocytes of rheumatoid arthritis(RA)by regulating HIF-1α signal pathway.Methods Three genera-tions of RA synovial cells were divided into blank control group,LEF group and Tripterygium wilfordii polyglyco-sides group.The blank control group was added with the same volume of DMEM culture medium.The drug group was treated with LEF(concentration 0.2 mg/ml)and Tripterygium wilfordii polyglycosides(concentration 0.03 mg/ml),the proliferation and apoptosis of synovial cells were detected by flow cytometry,the expression of IL-1 β,TNF-α,ANGPTL-4 and VEGF was detected by ELISA,the expression of HIF-1α mRNA was detected by qRT-PCR,and the expression of HIF-1 α,Beclin-1 and BNIP3 protein was detected by Western blot.Results Com-pared with Tripterygium wilfordii polyglycosides group,the expression of IL-1 α,TNF-α,ANGPTL-4 and VEGF in synovial supernatant of LEF group decreased;compared with the blank control group,the expression of HIF-1αmRNA in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious;compared with the blank control group,the protein expressions of HIF-1α,Bec-lin-1 and BNIP3 in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious.Conclusion LEF can inhibit the expression of inflammatory factors in RA synovial cells,inhibit HIF-1α signaling pathway,inhibit the expression of autophagy-related genes Beclin-1 and BNIP3,and improve the pathological state of synovitis.

italic>Lonicera Linn. is the largest genus of family Caprifoliaceae, which has a long history and abundant resources in China. Due to its ornamental and medicinal properties, the species of Lonicera shows outstanding economic value. However, affected by the huge demand and high price stimulation, there is a serious mixing phenomenon on the market. In this study, high-throughput sequencing technology was used to analyze the analysis of L. angustifolia Wallich ex Candolle var. myrtillus (Hook. f. & Thomson) Q. E. Yang, L. myrtillus Hook. f. et Thoms. var. cyclophylla Rehd, L. szechuanica Batal and L. tangutica Maxim to sequence and assemble their chloroplast (CP) genomes, and to conduct structural comparisons and phylogenetic studies. The results showed that the chloroplast genomes of the four species showed a typical circular tetrad structure, with a total length of 154 608-163 413 bp and a total GC content of 37.93%-38.42%. A total of 128-129 genes were annotated, including 83-84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. A total of 53-68 SSRs and 133-745 long repeats were detected by chloroplast repeat structure analysis. Phylogenetic studies showed that 21 species of Lonicera medicinal plants could be significantly clustered into one branch, among which the relatives of L. angustifolia and L. szechuanica were close, and the kinship of L. myrtillus and L. tangutica was close. This study is the first comprehensive study of the chloroplast genome and phylogenetic relationship of Loicera species, and the experimental results provide a scientific basis for revealing the genetic information, species evolution and genetic diversity of Lonicera species.

Objective To investigate the effect of butorphanol combined with parecoxib sodium on patient-controlled intravenous analgesia(PCIA)after uvulo-palato-pharyngo-plasty(UPPP).Methods Eighty patients who were admitted to our hospital from October 2021 to May 2023 and planned to receive UPPP were collected,and they were randomly assigned to the paroxicib sodium group(D group),the butorphanol low-dose group(B1 group),the butorphanol medium dose group(B2 group),and the butorphanol high-dose group(B3 group),with 20 cases in each group.Patients in the D group received 40 mg of paroxycoxib sodium with 0.9% sodium chloride injection for analgesia,and patients in the B1 group,the B2 group,and the B3 group were combined with 3.0 μg·kg-1·h-1,4.0 μg·kg-1·h-1,and 5.0 μg·kg-1·h-1 of butorphanol respectively on the basis of D group.The heart rate and mean arterial pressure before PCIA and 2 hours,12 hours,24 hours,and 48 hours after PCIA were compared among the four groups;the pain visual analogue scale(VAS)score,Ramsay score 2 hours,12 hours,24 hours,and 48 hours after PCIA were compared among the four groups;the number of PCIA compression,and incidence of adverse reactions were recorded.Results There was no statistically significant difference in the heart rate or mean arterial pressure before PCIA and 2 hours,12 hours,24 hours,and 48 hours after PCIA among the four groups(P>0.05).Compared with the D group,the VAS scores 2 hours,12 hours,24 hours,and 48 hours after PCIA of the B1,B2,and B3 groups significantly decreased(P<0.05),and the higher the dose of butorphanol,the lower the VAS score(P<0.05).Compared with the D group,the Ramsay scores 2 hours,12 hours,24 hours,and 48 hours after PCIA of the B1,B2,and B3 groups obviously increased(P<0.05),and the higher the dose of butorphanol,the higher the Ramsay score(P<0.05).The total incidence of adverse reactions in the B3 group was obviously higher than that in the D group,the B1 group,and the B2 group(P<0.05).Compared with the D group,patients in the B1,B2,and B3 groups had significantly fewer PCIA compressions(P<0.05),and the higher the dose of butorphanol,the fewer the PCIA compressions(P<0.05).Conclusion The effect of butorphanol combined with parecoxib sodium in PCIA after UPPP is better,and combined with 4.0 μg·kg-1·h-1 parecoxib sodium has more significant analgesic effect and higher safety.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.