Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.

Objective:To explore the influencing factors for pneumonia occurrence within three months in patients undergoing partial laryngectomy combined with radiotherapy, and to construct a nomogram prediction model for the risk of pneumonia occurrence.Methods:A total of 165 patients with laryngeal squamous cell carcinoma who underwent partial laryngectomy combined with postoperative radiotherapy in the Affiliated Cancer Hospital of Zhengzhou University from 2017 to 2023 were divided into three groups: a group without pneumonia, a low risk pneumonia group, and a medium to high risk pneumonia group according to the occurrence of pneumonia. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values of the mean dose to the larynx (Larynx-Dmean) and the mean dose to the pharyngeal constrictor muscles (PCM-Dmean) for predicting the occurrence of pneumonia. Logistic regression analysis was used to screen out the influencing factors of pneumonia within three months after partial laryngectomy combined with radiotherapy, and a nomogram prediction model was constructed.Results:Among the 165 patients, 59 were in the group without pneumonia, 60 were in the group with a low risk of pneumonia, and 46 were in the group with a medium to high risk of pneumonia. The overall incidence of pneumonia was 64.2% (106/165). ROC curve analysis showed that the area under the curve (AUC) of the Larynx-Dmean for predicting the occurrence of pneumonia was 0.876, and the optimal cutoff value was 60.8 Gy. When the Larynx-Dmean was >60.8 Gy, the incidence of pneumonia was 96.7%. The AUC of the PCM-Dmean for predicting the occurrence of pneumonia was 0.747, and the optimal cutoff value was 54.6 Gy. When the PCM-Dmean was >54.6 Gy, the incidence of pneumonia was 74.7%. The AUC of the Larynx-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.987, and the optimal cutoff value was 68.2 Gy. When the Larynx-Dmean was >68.2 Gy, the incidence of medium to high risk pneumonia was 100.0%. The AUC of the PCM-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.850, and the optimal cutoff value was 58.7 Gy. When the PCM-Dmean was >58.7 Gy, the incidence of medium to high risk pneumonia was 85.2%. Multivariate logistic regression analysis showed that the incidence of pneumonia was higher in patients with a history of smoking ( OR=1.54, 95% CI: 1.02-1.74), a higher smoking index ( OR=2.43, 95% CI: 1.16-7.59), a higher Larynx-Dmean ( OR=3.79, 95% CI: 1.25-6.49), and a higher PCM-Dmean ( OR=2.44, 95% CI: 1.53-3.16). A nomogram prediction model for the risk of pneumonia and medium to high risk pneumonia within three months after partial laryngectomy combined with radiotherapy was successfully constructed, with C indices of 0.78 and 0.98, respectively, which had good predictive performance and clinical efficacy. Conclusions:When the Larynx-Dmean was >60.8 Gy and the PCM-Dmean was >54.6 Gy for postoperative radiotherapy after partial laryngectomy, the possibility of pneumonia occurrence in patients within three months increased significantly. Smoking history, smoking index, Larynx-Dmean, and PCM-Dmean were independent influencing factors for the occurrence of pneumonia. The nomogram prediction model constructed based on this can guide clinicians to take intervention measures to prevent the occurrence of pneumonia in patients with laryngeal cancer.

Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.

Objective:To explore the influencing factors for pneumonia occurrence within three months in patients undergoing partial laryngectomy combined with radiotherapy, and to construct a nomogram prediction model for the risk of pneumonia occurrence.Methods:A total of 165 patients with laryngeal squamous cell carcinoma who underwent partial laryngectomy combined with postoperative radiotherapy in the Affiliated Cancer Hospital of Zhengzhou University from 2017 to 2023 were divided into three groups: a group without pneumonia, a low risk pneumonia group, and a medium to high risk pneumonia group according to the occurrence of pneumonia. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values of the mean dose to the larynx (Larynx-Dmean) and the mean dose to the pharyngeal constrictor muscles (PCM-Dmean) for predicting the occurrence of pneumonia. Logistic regression analysis was used to screen out the influencing factors of pneumonia within three months after partial laryngectomy combined with radiotherapy, and a nomogram prediction model was constructed.Results:Among the 165 patients, 59 were in the group without pneumonia, 60 were in the group with a low risk of pneumonia, and 46 were in the group with a medium to high risk of pneumonia. The overall incidence of pneumonia was 64.2% (106/165). ROC curve analysis showed that the area under the curve (AUC) of the Larynx-Dmean for predicting the occurrence of pneumonia was 0.876, and the optimal cutoff value was 60.8 Gy. When the Larynx-Dmean was >60.8 Gy, the incidence of pneumonia was 96.7%. The AUC of the PCM-Dmean for predicting the occurrence of pneumonia was 0.747, and the optimal cutoff value was 54.6 Gy. When the PCM-Dmean was >54.6 Gy, the incidence of pneumonia was 74.7%. The AUC of the Larynx-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.987, and the optimal cutoff value was 68.2 Gy. When the Larynx-Dmean was >68.2 Gy, the incidence of medium to high risk pneumonia was 100.0%. The AUC of the PCM-Dmean for predicting the occurrence of medium to high risk pneumonia was 0.850, and the optimal cutoff value was 58.7 Gy. When the PCM-Dmean was >58.7 Gy, the incidence of medium to high risk pneumonia was 85.2%. Multivariate logistic regression analysis showed that the incidence of pneumonia was higher in patients with a history of smoking ( OR=1.54, 95% CI: 1.02-1.74), a higher smoking index ( OR=2.43, 95% CI: 1.16-7.59), a higher Larynx-Dmean ( OR=3.79, 95% CI: 1.25-6.49), and a higher PCM-Dmean ( OR=2.44, 95% CI: 1.53-3.16). A nomogram prediction model for the risk of pneumonia and medium to high risk pneumonia within three months after partial laryngectomy combined with radiotherapy was successfully constructed, with C indices of 0.78 and 0.98, respectively, which had good predictive performance and clinical efficacy. Conclusions:When the Larynx-Dmean was >60.8 Gy and the PCM-Dmean was >54.6 Gy for postoperative radiotherapy after partial laryngectomy, the possibility of pneumonia occurrence in patients within three months increased significantly. Smoking history, smoking index, Larynx-Dmean, and PCM-Dmean were independent influencing factors for the occurrence of pneumonia. The nomogram prediction model constructed based on this can guide clinicians to take intervention measures to prevent the occurrence of pneumonia in patients with laryngeal cancer.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

Objective To investigate the protective effect of curcumin (Cur) against arsenic-induced neuroimmune toxicity and the underlying molecular mechanisms in vivo. Methods Eighty SPF female C57BL/6 mice were randomly assigned to four groups: a control group, an arsenic-treated group, a Cur-treated group and an arsenic+Cur group, with 20 mice in each group. The control group received distilled water; the arsenic-treated group was given 50 mg/L NaAsO₂ in the drinking water; the Cur-treated group was gavaged with 200 mg/kg of curcumin for 45 days; and the arsenic+Cur group received distilled water and was gavaged with 200 mg/kg of curcumin. Y-maze and Morris water maze experiments were conducted to assess the learning and memory ability of the mice. Western blot analysis was used to detect protein levels of blood-brain barrier tight junction proteins zonula occludens protein 1(ZO-1) and claudin 5, T lymphocyte subpopulation CD4 and CD8, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules JAK2 and STAT3. Real-time PCR was used to assess the mRNA levels of CD4⁺ T lymphocyte subsets type 1 T helper (Th1), Th2, Th17 and regulatory T cells (Treg) transcription factors and cytokines in hippocampus. Results Compared with the control group, the arsenic-treated group showed a significantly decreased correct rate, increased latency to reach the platform on the third and fifth days, and reduced times of crossing the platform. The expression of ZO-1 and claudin 5 protein decreased significantly, and the protein levels of CD4 and CD8 were up-regulated. The mRNA levels of Th1, Th17, and Treg transcription factor T-box expressed in T cell(T-bet), retinoid-related orphan receptor gamma t(RORγt), and forkhead box protein 3(FOXP3) in the arsenic-treated group were decreased. Th1 and Th17 cytokines interferon γ(IFN-γ) and interleukin 17(IL-17) were markedly decreased. In contrast, the mRNA levels of the Th2 transcription factor GATA binding protein 3(GATA3) and cytokine IL-4 in arsenic-treated group were higher than those in the control group. Furthermore, the protein levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) increased. Compared with the arsenic-treated group, the arsenic+Cur group demonstrated a significantly increased correct rate, decreased latency to reach the platform on the third and fifth days, and increased times of crossing the platform. The protein expression levels of ZO-1 and claudin 5 increased significantly, and the protein levels of CD4 and CD8 were down-regulated. The mRNA levels of Th2 transcription factor GATA3 and cytokine IL-4 were decreased. The mRNA levels of Th17 transcription factor RORγt and cytokine IL-17 were markedly increased. Furthermore, the protein levels of p-JAK2 and p-STAT3 decreased. Conclusion Through inhibiting the JAK2/STAT3 signaling pathway, curcumin could improve arsenic-induced decline in learning and memory abilities in mice, reverse the destruction of blood-brain barrier permeability of innate immune system components in arsenic-exposed mice, and antagonize arsenic-induced increase in the number of renal CD4 and CD8 molecule as well as the imbalance of CD4⁺ T lymphocyte subsets (Th1, Th2, Th17 and Treg), ultimately counteracting arsenic-induced neurotoxicity.
Animals ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Female ; Curcumin/pharmacology* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Arsenic/toxicity*

Objective To explore the diagnostic value of long non-coding RNA nuclear-enriched abundant transcript 1(LncRNA NEATl)and microRNA(miR)-424-5p in the diagnosis of endometriosis(EM)combined with infertility and its application value in disease staging.Methods A total of 232 EM patients who visited Shijiazhuang Maternal and Child Health Hospital from October 2021 to October 2023 were selected as the study subjects,120 patients with EM combined with infertility were used as the infertility group,and 112 patients with pure EM were regarded as the control group.The infertility group was separated into r-AFS stages Ⅰ～Ⅱ(n=27),r-AFS stage Ⅲ(n=45),and r-AFS stage Ⅳ(n=48)according to the American r-AFS staging standards,and qRT-PCR method was applied to detect the expression levels of serum LncRNA NEAT1 and miR-424-5p.Receiver operating characteristic(ROC)curve was applied to analyze the value of serum LncRNA NEAT1 and miR-424-5p in diagnosing EM combined with infertility,and multivariate Logistic regression was applied to analyze the influencing factors of EM combined with infertility.Bioinformatics analysis of LncRNA NEAT1 targeting miR-424-5p was performed on the TargetScanHuman website.Pearson method was applied to analyze the correlation between serum LncRNA NEAT1 and miR-424-5p expression levels in patients with EM combined with infertility.Results Differences of serum LncRNA NEAT1(1.16±0.15 vs 1.02±0.13),pelvic surgery history ratio(17.50％vs 1.79％),miR-424-5p(0.92±0.11 vs 1.04±0.12)expression levels between infertility group and control group were significant,and the differences were significant(t=7.753,16.018,7.974,all P＜0.05).Serum LncRNA NEAT1(1.05±0.10,1.14±0.14,1.24±0.19)increased and miR-424-5p(0.99±0.12,0.93±0.11,0.87±0.10)decreased in r-AFS stage Ⅰ～Ⅱ,Ⅲ,Ⅳ patients,and the differences were significant(F=13.528,10.910,all P＜0.05).There was a targeting relationship between LncRNA NEAT1 and miR-424-5p,and there was a negative correlation between serum LncRNA NEAT1 and miR-424-5p expression levels in EM patients with infertility(r=-0.431,P＜0.05).The AUCs of serum LncRNANEAT1,miR-424-5p,and combined diagnosis for EM combined with infertility were 0.782,0.719 and 0.835,respectively,and the AUC of combined diagnosis was better than that of individual detection(Z=2.625,3.861,P=0.009,0.001).LncRNA NEAT1 was a risk factor for EM combined with infertility,while miR-424-5p was a protective factor(all P＜0.05).Conclusion The expression level of serum LncRNA NEAT1 is increased and miR-424-5p is decreased in EM patients with infertility,both of which are related to the disease stage and the occurrence of infertility.

Objective:To explore the regulatory effects of long non-coding RNA H19(LncRNA H19)on the osteogenic differentia-tion of MC3T3-E1 cells under the stimulation of advanced glycation end products(AGEs).Methods:MC3T3-E1 cells were cultured under the stimulation of 10 μg/mL AGEs.The cells were observed by alkaline phosphatase(ALP)staining after 7 d and alizarin red staining after 21 d culture respectively.Cell transfection technology was used to overexpress LncRNA H19 in the cells,RT-qPCR was used to detect the mRNA expression levels of ALP,Runx-2,OCN,SP7 before and after transfection of LncRNA H19.Western blotting was used to detect the protein expression of Runx-2 and[3-catenin in the cells.Results:Under the stimulation of AGEs,the ALP stai-ning color of MC3T3-E1 cells became lighter,the formation of calcified nodules was reduced,the mRNA expression levels of ALP,Runx-2,OCN,SP7 and LncRNA H19 were decreased(P＜0.05),and the protein expression level of Runx-2 was decreased.After transfection of LncRNA H19(lv-H19),the mRNA expression of LncRNA H19 was significantly up-regulated(P＜0.05),the mRNA expression of ALP,Runx-2,OCN and SP7 genes was increased(P＜0.05),ALP staining was deeper,and the expression of β-catenin was increased.Conclusion:Under the stimulation of AGEs,LncRNA H19 may affect the osteogenic differentiation of MC3T3-E1 cells by activating the expression of WNT/[3-catenin.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).