Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

Objective To investigate the relationship between the expression of serum microRNA-326(miR-326)and microRNA-623(miR-623)in non-small cell lung cancer(NSCLC)patients and their clinical pathological characteristics and prognosis.Methods A total of 114 NSCLC patients diagnosed in our hospital from March 2019 to June 2020 were collected as study subjects as case group,123 healthy individuals who underwent physical examination were as the control group.According to the 3-year prognosis,patients were separated into a survival group of 71 cases and a death group of 43 cases.Patient related clinical data were collected,real-time fluorescence quantitative PCR method was applied to detect the expression levels of miR-326 and miR-623 in various serum samples;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-326 and miR-623 in NSCLC patients and their 3-year prognosis;Cox proportional risk regression model was applied to analyze the influencing factors of 3-year prognosis in NSCLC patients.Results The expression levels of serum miR-326 in the case group and control group were 0.64±0.15 and 1.02±0.23,respectively,and the expression levels of miR-623 were 0.56±0.10 and 0.98±0.15,respectively.The difference between the two groups was statistically significant(P＜0.05).The proportions of patients with low expression of miR-326 and miR-623 in low differentiation,TNM stage Ⅲ+Ⅳ,and lymph node metastasis were higher than those in high differentiation,TNM stage Ⅰ and Ⅱ,and no lymph node metastasis(P＜0.05).The 3-year survival rates of patients with low expression of miR-326(20/55,36.36％)and miR-623(27/61,44.26％)in the serum of NSCLC patients were lower than those of patients with high expression of miR-326(51/59,86.44％)and miR-623(44/53,83.02％)(Log Rank x2=32.060,22.812,P＜0.05).Serum miR-326[(0.55±0.09)vs.(0.69±0.11)]and miR-623 levels[(0.48±0.08)vs.(0.61±0.10)]of patients in the death group were significantly lower than those in the survival group(P＜0.05).The area under the curve(AUC)for poor prognosis of serum miR-326 and miR-623 alone and in combination in patients diagnosed with NSCLC were 0.828(95％CI:0.754 to 0.901),0.763(95％CI:0.671 to 0.855),and 0.903(95％CI:0.849 to 0.958),respectively.The proportions of patients with TNM stage Ⅲ+Ⅳ,lymph node metastasis,low expression of miR-326 and low expression of miR-623in the death group were higher than those in the survival group(P＜0.05).MiR-326 and miR-623 were protective factors affecting 3-year mortality in NSCLC patients,while TNM staging and lymph node metastasis were independent risk factors affecting 3-year mortality in NSCLC patients(P＜0.05).Conclusion The low expression of miR-326 and miR-623 may be involved in the occurrence and development of lung cancer,which is closely related to the clinical pathological characteristics and poor prognosis of patients.

Objective To explore the predictive value of glucose metabolism and lipid metabolism indexes for in-stent restenosis(ISR)in patients with arteriosclerosis obliterans(ASO)of lower limbs after surgery.Methods A total of 160 patients with ASO of lower limbs admitted to the Second Affiliated Hospital of Zhengzhou University and Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2018 to October 2021 were selected as the research subjects.All patients were treated with percutaneous transluminal angioplasty combined with stent implantation and were followed up for 1 year.Patients were divided into the ISR group(n=59)and the non-ISR group(n=101),according to the incidence of ISR during the follow-up period.General clinical data of patients in the two groups were collected.Univariate analysis was performed to preliminarily screen out the influencing factors for ISR,and the selected indexes were further analyzed by multivariate logistic regression to analyze the influencing factors for the occurrence of ISR in patients with ASO of lower limbs after surgery.The receiver operating characteristic(ROC)curve was used to analyze the value of the glucose metabolism and lipid metabolism indexes one day before discharge alone and their combination in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery.The net benefit rate of predicting the occurrence of ISR in patients with ASO of lower limbs by the levels of glucose metabolism and lipid metabolism indexes one day before discharge alone and their combination was analyzed through the decision curve.Results Among the 160 patients,59 developed ISR,with an incidence rate of 36.88％.There was no significant difference in age,gender,alcohol consumption,complications,affected side,Fontaine stage,fasting plasma glucose,and serum triglycerides of patients between the ISR group and the non-ISR group(P＞0.05);the proportion of smokers and the levels of glycosylated hemoglobin A1c(HbA1c)in peripheral blood and low-density lipoprotein(LDL)in serum of patients in the ISR group were significantly higher than those in the non-ISR group,while the level of high-density lipoprotein(HDL)in serum was significantly lower than that in the non-ISR group(P＜0.05).Multivariate logistic regression analysis showed that the elevated levels of HbA1 c in peripheral blood and LDL in serum were risk factors for ISR in patients with ASO of lower limbs after surgery(odds ratio＞1.00,P＜0.05),and the increased level of HDL in serum was the protective factor for ISR in patients with ASO of limbs after surgery(odds ratio＜1.00,P＜0.05).The ROC curve showed that the area under the curve of peripheral blood HbA1c,serum LDL and HDL levels alone and their combination in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery was 0.717,0.761,0.654,and 0.824,respectively;the specificity was 0.861,0.792,0.851,and 0.663,respectively;and the sensitivity was 0.525,0.678,0.424,and 0.864,respectively.The decision curve showed that the net benefit rate for the combination of peripheral blood HbA1c,serum LDL and HDL levels one day before discharge in predicting the occurrence of ISR in patients with ASO of lower limbs after surgery was higher than that of prediction by the said indexes alone.Conclusion Glucose metabolism index peripheral blood HbA1c and lipid metabolism indexes serum LDL and HDL have certain predictive values for the occurrence of ISR in patients with ASO of lower limbs after surgery,and the net benefit rate of the joint prediction of the three indexes is higher.

Objective:To explore the clinical value of introducing 68Ga PSMA PET / CT into the prostate cancer(PCa)screening clinic, and to analyze the incidence rate and biopsy of PCa in the screening clinic of our hospital. Methods:The data of the people who participated in PCa screening in the urology screening clinic of our hospital from March 2021 to November 2021 were retrospectively analyzed. Serum PSA was used as the screening index. The subjects with PSA≥4ng/ml were first examined by mpMRI to find suspicious nodules, and the positive ones were further examined by 68Ga-PSMA PET/CT to determine the lesions.The puncture target was outlined, and systematic+ targeted puncture was conducted under ultrasound guidance. The age, PSA distribution, puncture detection rate, Gleason score and clinical stage of patients with PCa were recorded. Results:A total of 1 079 subjects were included in the screening, with an average age of (63.9±9.9)(ranging 40-92) years old, and 249 patients (23.1%, 249/1 079) with PSA≥4ng/ml. Among them, 87 cases (87/249, 34.9%) received mpMRI, and 34 cases (34/249, 13.7%) had PI-RADS score ≥3 points. These 34 patients with suspected nodules on MRI were further scanned with 68Ga-PSMA PET/CT, and 11 cases (11/249, 4.4%) had abnormal uptake of PSMA nuclide. A total of 32 patients (12 patients with PSA abnormalities and 20 patients with positive imaging) finally received prostate biopsy, and 11 patients were diagnosed with PCa, with a positive detection rate of 34.4% (11/32), accounting for 1.0% (11/1 079) of the screening population. Among them, 20 patients with positive imaging (9 patients with only mpMRI positive and 11 patients with both mpMRI and 68Ga-PSMA PET/CT positive) underwent system + targeted fusion biopsy, and the positive rate was 45% (9/20). 12 patients (only PSA abnormal) underwent routine systematic puncture biopsy, and the positive detection rate was 16.7% (2/12). The difference between the two groups was statistically significant ( P<0.05). Among the patients with confirmed PCa, 27.3% (3/11) had Gleason score less than 7, and 72.7% (8/11) had Gleason score≥7. Localized PCa (≤T 2) accounted for 45.4% (5/11), local progression (T 3-T 4) accounted for 18.2% (2/11), and metastatic PCa suggested by 68Ga-PSMA PET/CT accounted for 36.4% (4/11), including 3 systemic multiple bone metastases and one bone metastasis with distant lymph node metastasis. Clinically significant PCa accounted for 90.9% (10/11) of the confirmed patients, and the proportion of high-risk patients in localized or locally advanced PCa was 71.4% (5/7). Conclusions:In PCa screening, if 68Ga-PSMA PET/CT is introduced on the basis of conventional mpMRI, the detection rate of clinically meaningful PCa can be improved. Combined with targeted puncture, tumor lesions can be found early and the screening efficiency of PCa can be improved. In this study, the detection rate of PCa in outpatient screening reached 1.0%. In confirmed cases, the proportion of high-risk patients and metastatic patients was higher.

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies ; HIV Infections/epidemiology* ; HIV-1 ; Homosexuality, Male ; Humans ; Immunoenzyme Techniques ; Incidence ; Male ; Sexual and Gender Minorities

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities