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.

OBJECTIVE To standardize the rational clinical use of romosozumab in China， define suitable patient populations， optimize full-course treatment strategies， and strengthen medication risk management.METHODS This consensus was initiated by the Pharmacy Administration Committee of Guangdong Province Hospital Association and registered on the International Practice Guidelines Registry Platform. Twenty-five experts in pharmacy and orthopedics were organized to identify 7 core clinical questions through 2 rounds of questionnaires and seminars. Chinese and English databases were systematically retrieved， and the Grading of Recommendations Assessment， Development and Evaluation approach was used to assess evidence quality and recommendation strength and to formulate consensus recommendations， which were refined based on expert review.RESULTS Seven recommendations were developed， covering the applicable populations of romosozumab， sequential and switching therapy， and management of fractures and cardiovascular risk during treatment. The pharmaceutical characteristics of romosozumab， as well as other key points for clinical application， including efficacy monitoring， management of missed doses， contraindications， major adverse reactions， and medication adherence， were also summarized.CONCLUSIONS This consensus provides evidence-based guidance and practical reference for the safe， effective， and standardized use of romosozumab in Chinese patients， which may facilitate individualized treatment of patients with osteoporosis at high fracture risk and reduce fracture risk.

Objective To investigate the potential mechanism of action of polygonatum odoratum in treating Alzheimer's disease through the utilization of network pharmacology and molecular docking techniques.Methods The methods employed include target screening,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and molecular docking simulations to assess the binding interactions between the active compounds in polygonatum odoratum(POD)and the key target proteins associated with Alzheimer's disease.Subsequently,lipopolysaccharide(LPS)was used to induce an inflammatory cell model in BV2 microglial cells.After treating the cell model with POD extract for 24 hours,the cells were collected,and the expression of the target genes were detected by Real-time PCR.Results Eight active ingredients and 172 targets of POD were screened.The biological processes such as protein phosphorylation and signal transduction,protein binding and ATP binding were obtained by GO functional analysis.KEGG enrichment yielded PI3K/Akt,cAMP and other signaling pathways.The molecular docking result showed that the active ingredient of POD had well binding activity with epidermal growth factor receptor(EGFR),proto-oncogene tyrosine-protein kinase Src(SRC),tumor necrosis factor(TNF),STAT3.Through Real-time PCR experiments,the gene expressions of inducible nitric oxide synthase(iNOS),prostaglandin G/H synthase 2(PTGS2),interleukin(IL)-6,and IL-1β in the LPS-induced inflammatory cell model were significantly upregulated.After treating the inflammatory model with POD extract for 24 hours,the expression of TNF-α was significantly reduced,the expression of STAT3 was upregulated,there were no significant changes in the expressions of SRC and EGFR.Conclusion Network pharmacology suggests polygonatum odoratum's potential anti-Alzheimer's effects may be mediated through its interaction with targets such as EGFR,TNF,SRC,and STAT3.The experimental results suggest that polygonatum odoratum exerts an anti-inflammatory effect by acting on TNF-α,which may further alleviate the symptoms of Alzheimer's disease.

Objective:To investigate the association between estimated glomerular filtration rate (eGFR) and the onset and progression of type 2 diabetic retinopathy (DR).Methods:Observational studies on the relationship between eGFR and the progression of DR were searched in the databases of PubMed, Web of Science, Foreign Medical Literature Retrieval Service (FMRS), China National Knowledge Infrastructure and Wanfang data. The search period was from the inception of the databases to January 20, 2024. Meta-analysis of the association between eGFR and the onset and progression of DR with the research data was conducted by using Review Manager 5.3 and Stata 15.0, the weighted mean difference (WMD) and 95% confidence interval (CI) were calculated. Sensitivity analysis and Egger′s test were performed to assess the result stability and publication bias.Results:A total of 30 studies involving 119 142 patients with type 2 diabetes were included in the analysis. The eGFR in the DR group was significantly lower than that in the non-DR group (WMD=8.11, 95% CI: 5.97-10.25, P<0.001). Subgroup analysis by DR type revealed that patients with diabetic macular edema (WMD=7.61, 95% CI: 3.82-11.40) and proliferative DR (WMD=17.40, 95% CI: 10.13-24.66) had significantly lower eGFR when compared to that in non-DR group (both P<0.001). The subgroup analysis results according to different DR diagnostic criteria showed that both the 2003 International DR Grading Standard Group (WMD=8.55, 95% CI: 5.29-11.81) and the 2002 International Clinical DR Severity Grading Standard Group (WMD=10.70, 95% CI: 7.99-13.41) indicated the statistically significant differences in eGFR in relation to the occurrence and progression of DR. Conclusion:The decrease of eGFR is closely related to the occurrence and progression of DR.

Objective:To investigate the adjunctive diagnostic value of retinal imaging structural parameters combined with apolipoprotein E (ApoE) gene polymorphisms for Alzheimer′s disease (AD).Methods:It was a case-control study, 71 confirmed AD patients who attended the Department of Neurology in Sichuan Provincial People′s Hospital from May 2023 to June 2024 and 156 healthy medical checkups who participated in medical checkups in the Health Management Center were continuously with convenience sampling method; the subjects were included as the AD case group and healthy control group, respectively. Optical coherence tomography (OCT) was used to measure the structural parameters of retinal imaging such as the thickness of the retinal nerve fiber layer (RNFL) and the retinal nerve fiber layer-inner plexiform layer (RNFL-IPL) in the study subjects. Information on demographic characteristics and disease history of the study participants were collected through a questionnaire, and venous blood was collected to test for ApoE gene polymorphisms. The retinal imaging structural parameters, ApoE gene polymorphisms and other related indicators were included in a multifactorial logistic regression model to analyze the main factors affecting the risk of AD. Based on the results of the multifactorial analysis, the receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUC) were calculated to evaluate the efficacy of different models in the adjunctive diagnosis of AD.Results:Of the 227 study subjects included in the analysis, 153 were females and 74 were males; there were 71 cases in the AD case group with a mean age of (66.73±8.83) years, and there were 156 subjects in the healthy control group with an average age of (61.95±8.21) years. Educational attainment of elementary school and below ( OR=4.683, 95% CI: 2.133-10.282), living visual acuity<0.5 ( OR=2.716, 95% CI: 1.12-6.583), and carrying ≥1 ApoE ε4 genes ( OR=5.331, 95% CI: 2.309-11.891) were positively correlated with the risk of AD. RNFL thickening ( OR=0.923, 95% CI: 0.854-0.998) was negatively associated with the risk of AD (all P<0.05). The AD risk assessment model (Model 4), which included fundus imaging features and ApoE gene polymorphisms, had the highest predictive efficacy (AUC=0.857, P<0.001). Conclusion:Retinal imaging structural parameters differ significantly between AD patients and healthy examinees, and a risk assessment model combining retinal imaging structural parameters and ApoE gene polymorphisms has high predictive value and is expected to serve as an auxiliary diagnostic tool for AD.

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.