BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To explore the influencing factors of neonatal pneumonia complicated with myocardial damage and Th1/Th2 cytokines,and construct a line chart model.Methods A total of 390 neonates with pneumonia who were treated in Mianyang People's Hospital were selected as the study subjects and randomly divided into a modeling cohort(n=273)and a validation cohort(n=117)according to a 7∶3 ratio.They were further divided into myocardial damage group and non-myocardial damage group according to whether they had concurrent myocardial damage.Enzyme linked immunosorbent assay(ELISA)was used to measure Th1/Th2 cytokines(IFN-γ,IL-6,TNF-α,IL-4,IL-2 and IL-10),and the Mindray BS-280 automatic biochemical analyzer was used to measure hs-cTn I,CK-MB,LDH and CK.Logistic regression equation was used to screen the influencing factors of neonatal pneumonia complicated with myocardial damage.R software was used to construct a line chart model,and the receiver operating characteristic curve(ROC)and area under the ROC curve(AUC)were used to analyze the predictive ability of the model.The Hosmer-Lemeshow goodness-of-fit test was used,and a calibration curve was drawn to evaluate the calibration of the model.The decision curve analysis(DCA)was used to evaluate the clinical effectiveness.Results The incidence of myocardial damage in 390 neonates with pneumonia was 28.21%.Modeling cohort and validetion cohort,the 1min Apgar score in the myocardial damage group was lower than that in the non-myocardial damage group(t=3.314,2.619),and CK-MB,LDH,CK,hs-cTnI,IL-2,IFN-γ,TNF-α,IL-6,IL-10 and IL-4 were higher than those in the non-myocardial damage group(t=5.805～18.914),and the proportions of severe pneumonia,low birthweight infant,premature infants were higher than those in the non-myocardial damage group(χ2=4.464～41.497),and the differences were statistically significant(all P<0.05),respectively.The Logistic regression equation showed that low birth weight,1-minute Apgar score,premature birth,hs-cTnI,IL-2,IFN-γ,IL-6 and IL-4 were factors affecting neonatal pneumonia complicated with myocardial damage(Wald χ2=10.330～14.328,all P<0.05).The AUC(95%CI)of the nomogram model constructed based on the factors affecting neonatal pneumonia complicated with myocardial damage was 0.880(0.839～0.921)in the modeling cohort and 0.910(0.856～0.964)in the validation cohort,with slopes of the calibration curves close to 1,and the clinical net benefit rate was the highest in the ranges of 0.1～0.8 and 0.0～0.7.Conclusion The nomogram model,which includes Th1/Th2 cytokines,hs-cTnI,1-minute Apgar score,premature infants and low-birth-weight infants has high predictive value for neonatal pneumonia complicated with myocardial damage.It can help clinicians identify high-risk populations,take reasonable diagnostic and treatment measures,and reduce the risk of myocardial damage.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

Carbon dioxide(CO2),a colorless,odorless,low-density negative contrast agent with no nephrotoxicity or allergic reactions,has seen increasingly widespread application in the field of vascular imaging in recent years,particularly in patients with iodine allergy or renal insufficiency.When combined with digital subtraction angiography,CO2 angiography has demonstrated high-quality imaging in various arterial and venous sites such as the abdominal aorta,renal arteries,iliac arteries,lower limb arteries,and inferior vena cava.It has also shown safety and efficacy in clinical scenarios such as peripheral arterial disease,dialysis access evaluation,and transjugular intrahepatic portosystemic shunt procedures.This review systematically summarizes domestic and international research progress on CO2 angiography,outlines its physicochemical properties,injection dosages and parameters,clinical indications,and imaging characteristics,and compares its image quality with that of iodine-based contrast agents.Common complications,their mechanisms,and preventive measures are also discussed.Although the image quality of CO2 is slightly inferior to that of iodine agents,it remains sufficient for most diagnostic and therapeutic needs,with a low overall incidence of mainly mild and transient adverse effects.With the development of automated injection systems and digital variance angiography technology,CO2 imaging quality is expected to continue improving,and its application scope is likely to expand further.Future efforts should focus on strengthening multicenter clinical research and establishing standardized operational protocols to promote the broader adoption and regulated use of this technology.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective:To evaluate the potential value of 18×10 3 translocator protein (TSPO) radioligand ( N, N-diethy1-2-(2-(4-(2- 18F-fluoroethoxy) phenyl)-5, 7-dimethylpyrazolo[1, 5-A]pyrimidin-3-yl)acetamide, 18F-DPA-714) PET compared with conventional MR in the detection of autoimmune encephalitis (AE), the correlation with clinical symptoms, and the monitoring of immunotherapy efficacy in patients with AE. Methods:From December 2021 to June 2024, 45 AE patients (17 males, 28 females, age (38.3±17.0) years) diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and 10 healthy volunteers (7 males, 3 females, age (28.7±5.1) years) were enrolled in this prospective study. All participants underwent baseline 18F-DPA-714 PET/MR scans, and 23 of these AE patients underwent further follow-up 18F-DPA-714 PET/MR scans. 18F-DPA-714 PET positivity was defined as having an uptake intensity threshold higher than the mean SUV ratio (SUVR)+ 2 s of the corresponding brain region in healthy controls. MR positivity was defined as abnormal hyperintensity in a specific brain region or multiple brain regions on the T 2 fluid attenuated inversion recovery (FLAIR). The positive detection rates of 18F-DPA-714 PET and MR was analyzed using McNemar χ2 test, and the differences in the uptake intensity (SUVR) of 18F-DPA-714 between symptomatic and non-symptomatic groups, and between remission and non-remission groups after immunotherapy were compared using independent-sample t test or Wilcoxon rank sum test. Spearman rank correlation analysis was used to analyze the correlation between the changing rate of SUVR and the changing of the modified Rankin Scale (mRS) score before and after treatment. Results:The positive detecting rate of 18F-DPA-714 PET for AE was significantly higher than that of MR (73.3%(33/45) vs 35.6%(16/45); χ2=11.56, P=0.001). The cerebellar SUVR of ataxia patients was significantly higher than that of asymptomatic patients (1.22(1.06, 1.33) vs 1.08(0.99, 1.20); Z=-2.14, P=0.034). Follow-up imaging showed that the SUVR of patients in the remission group after immunotherapy was significantly lower than that in the non-remission group ((-15.19±10.17)% vs (14.26±13.36)%; t=5.81, P<0.001). There was a significant correlation between the changing rate of SUVR and the changing of the mRS score before and after treatment ( rs=0.65, P<0.001). Conclusion:Compared with conventional MR, 18F-DPA-714 PET has a higher positive detecting rate for AE, and has the potential to reflect the clinical symptoms of AE and monitor the efficacy of immunotherapy.