BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Objective:To investigate the predictive value of regional cerebral oxygen saturation (rScO 2) for perioperative neurocognitive disorders (PND) in the preanalgesia of erector spinal plane block (ESPB) combined with parecoxib sodium in elderly patients undergoing radical lung cancer surgery. Methods:A total of 180 elderly patients with lung cancer treated inthe Sixth Affiliated Hospital of South China University of Technology (People's Hospital of Nanhai District) from June 2022 to June 2023 were selected. All patients underwent thoracoscopic radical resection of lung cancer, pre-analgesia by ESPB combined with parecoxib sodium, and rScO 2 was monitored by near infrared spectroscopy. Cognitive function was assessed at 1 d before surgery and 7 d after surgery, and the incidence of PND was determined according to the Z score method. Patients with PND were included in the observation group (21 cases) and those without PND were included in the control group (159 cases). The clinical data, preoperative and postoperative cognitive scale scores, and perioperative rScO 2 were compared between the two groups. Logistic regression model was used to analyze the risk factors of PND. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of rScO 2 to patients' PND. Results:Patients aged ≥75 years, postoperative incision infection, postoperative 1d visual analogue scale (VAS) ≥4 scores, intraoperative blood loss and operative time in the observation group were higher than those in the control group: 61.90%(13/21) vs.34.59%(55/159), 19.05%(4/21) vs. 3.77%(6/159), 42.86%(9/21) vs. 18.87%(30/159), (208.39 ± 61.05) ml vs. (172.45 ± 60.22) ml, (188.96 ± 62.13) min vs. (150.36 ± 52.17)min; the years of education in the observation group was shorter than that in the control group: (8.10 ± 2.25) years vs. (9.89 ± 2.04) years, there were statistical differences ( P<0.05). The scores of mini-mental state examination (MMSE), visual verbal learning test (VVLT), digital span test (DST1) and digital symbol test (DST2) at 7 d after surgery in both groups were lower than those befor surgery, and the scores of MMSE, VVLT, DST1 and DST2 at 7 d after surgery in the observation group were lower than those in the control group: (22.86 ± 2.05) scores vs. (24.85 ± 1.87) scores, (2.95 ± 1.95) scores vs. (4.83 ± 2.01) scores, (7.52 ± 1.83) scores vs. (9.04 ± 1.93) scores, (40.48 ± 5.05) scores vs. (44.35 ± 4.96) scores, there were statistical differences ( P<0.05). The decrease rate of rScO 2 from the baseline value at single lung ventilation 1 h (T 2) in the observation group was higher than that in the control group: (21.32 ± 5.13)% vs. (14.51 ± 5.02)%, there was statistical difference ( P<0.05). The results of Logistic regression analysis showed that rScO 2 reduction rate from the baseline value, age ≥75 years, postoperative 1 d after surgery VAS ≥4 scores, and operation time were independent risk factors for PND; the higher levels of rScO 2 at T 2 and after operation (T 3) were independent protective factors ( P<0.05). The results of ROC curve analysis showed that the area under the curve(AUC) of rScO 2 at T 2 and T 3 and the decrease rate of rScO 2 from the baseline value predicted that the PND in elderly patients with pre-analgesic radical lung cancer with ESPB combined with paracxib sodium were 0.742, 0.716 and 0.822, respectively, in which the AUC of the decrease rate of rScO 2 from the baseline value was the largest. Conclusions:rScO 2 can be used for predicting PND in the elderly patients with radical lung cancer after ESPB combined with parecoxib sodium, especiallythe predictive value of the decrease rate of rScO 2 from the baselinevalue is higher.

Objective:To construct a risk warning model for severe mycoplasma pneumoniae pneumonia(SMPP)children based on clinical data,laboratory indicators and imaging indicators.Methods:162 Mycoplasma pneumoniae pneumonia(MPP)children who were admitted in Foshan Women and Children Hospital from January 2021 to December 2023 were selected,64 SMPP children were included in severe group,the remaining 98 children were included in mild group.The general data,laboratory indicators and imaging indicators of the children were collected.The influencing factors for the occurrence of SMPP were analyzed by univariate and multivariate logistic regression models,and a risk warning model for the occurrence of SMPP children was constructed based on multivariate logistic regression model.The predictive value of the risk warning model for the occurrence of SMPP were analyzed by receiver operating characteristic(ROC)curve.Results:The proportion of 3 years old ≤ age＜6 years old,course of disease,body temperature,fever course,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),lactate dehydrogenase(LDH),cyanosis of lips,positive triconcave sign,pleural effusion,lesion site was the lower lobe,abnormal electrocardiogram and extrapulmonary manifestations in severe group were significantly higher than those in mild group(P＜0.05),there were no significant differences in gender,white blood cell count(WBC),neutrophil ratio and procalcitonin(PCT)between the two groups(P＞0.05).Multivariate logistic regression analysis model showed that,3 years old ≤age＜6 years old,high body temperature,long fever course,CRP elevated,ESR elevated,LDH elevated,cyanosis of lips,positive triconcave sign,pleural effusion,lesion site was the lower lobe,abnormal electrocardiogram and extrapulmonary manifestations were risk factors for the occurrence of SMPP(P＜0.05).ROC curve analysis showed that,the area under the curve(AUC)of the risk warning model was 0.829,the sensitivity was 84.82％,and the specificity was 78.15％,the actual prediction curve of the risk warning model was in good agreement with the prediction curve,the decision curve showed that,the threshold probability range of the model was 4.61％～88.14％.Conclusion:The risk warning model based on clinical multi parameters such as general data,laboratory indicators and imaging indicators has certain predictive value for the occurrence of SMPP.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Objective Tetanus is a serious infectious diseases with high mortality,which is an important global public health issue.This study aims to analyze the epidemiological burden and changing trends of tetanus in China from 1990 to 2021,providing a basis for disease prevention and control.Methods Epidemiological indicators and global socio-demographic index(SDI)related to tetanus in China were retrieved and collected from the 2021 Global Burden of Disease database(GBD 2021).The trend analysis of the incidence rate,mortality rate and disability-ad-justed life years(DALYs)rate of tetanus in China from 1990 to 2021 was conducted by Joinpoint 5.3 software.Results From 1990 to 2021,the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized disability-adjusted life years(DALYs)rate of tetanus in China decreased significantly(average annual percent change[AAPC]＜0,P＜0.001),with males being significantly higher than females.The crude incidence rate,crude mortality rate,and crude DALYs rate for all age groups showed overall declining trends,with the lar-gest decline in the 0-14 years age group.In 2021,the crude incidence rate,crude mortality rate,and crude DALYs rate of tetanus in the population aged 70-years were higher than those in the population aged 0-14,15-49,and 50-69 years groups.The ASIR,ASMR,and age-standardized DALYs rate of tetanus in China in 2021 were lower than the global level,only higher than those in the high SDI regions.Conclusion From 1990 to 2021,the disease burden of tetanus in China varied with gender and age,with an overall declining trend over time.It is necessary to strengthen tetanus health education for males and the ≥70 years population,and to improve the overall level of pri-mary prevention measures for tetanus.