Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate whether O6-methylguanine-DNA methyltransferase(MGMT)interference combined with temozolomide(TMZ)could enhance the therapeutic effect of temozolomide on human drug-resistant melanoma cells A375/TMZ.Methods A375/TMZ cells were randomly divided into 4 groups,control group(normal culture),MGMTsiRNA group(200 nmol·L-1 MGMTsiRNA),experimental group(1 600 μmol·L-1 TMZ)and combined group(transfection of MGMTsiRNA followed by addition of 1 600 μmol·L-1 TMZ).After 24 h of culture,the proliferation of cells in each group was analyzed by cell counting kit-8 method.Western blotting was used to detect the expression levels of poly ADP-ribose polymerase(PARP),cleaved PARP(cleaved-PARP),DNA-dependent protein kinase catalytic subunit(DNA-PKcs)and nuclear factor kappa-B(NF-κB)proteins in the cells.The expression and distribution of NF-κB proteins in the cells were detected by immunofluorescence.Results Cell inhibition rates of control,MGMTsiRNA,experimental and combined groups were 0,(3.45±1.53)％,(51.24±2.73)％and(70.69±4.48)％;the relative expression levels of PARP protein were 0.45±0.08,0.47±0.06,0.33±0.04,0.14±0.03;the relative expression levels of the cleaved-PARP protein were 0.01±0.02、0.01±0.01、0.18±0.03 and 0.36±0.04;the relative expression levels of DNA-PKcs protein were 0.09±0.03,0.07±0.02,0.32±0.02 and 0.39±0.04;the relative expression levels of NF-κB protein were 0.35±0.04,0.36±0.05,0.20±0.02 and 0.15±0.02.Compared with experimental group or control group,the differences of above indexes were all statistically significant(all P＜0.05).Immunofluorescence analysis showed that the average fluorescence intensity of NF-κB in control group,MGMTsiRNA group,experimental group and combined group were(5.26±1.05)％,(7.58±1.18)％,(10.56±1.99)％and(15.47±2.61)％;and compared with the cells in control group and MGMTsiRNA group,combined group showed NF-κB was significantly increased in the nucleus of tumor cells,and the difference was statistically significant(all P＜0.01).Conclusion MGMTsiRNA combined with TMZ further promotes proliferation inhibition and apoptosis of drug-resistant melanoma A375/TMZ cells by TMZ.

Objective:To explore the correlation between renal function and abdominal aortic hemodynamic parameters based on four-dimensional flow(4D Flow) MRI in patients with chronic kidney disease (CKD).Methods:A cross-section prospective study was conducted on 73 patients diagnosed with CKD at First People′s Hospital of Changzhou between March 2021 and May 2023, as well as 13 volunteers without kidney injury. According to the estimated glomerular filtration rate (eGFR), the subjects were divided into CKD 1-3 stage group ( n=34), CKD 4-5 stage group ( n=39), and control group ( n=13). All subjects underwent 4D Flow MRI examination of the abdominal aorta, measuring pulse wave velocity (PWV), peak velocity, and maximum wall shear stress (WSS) at the proximal plane (Plane_1) and the higher renal artery opening plane (Plane_2) of the abdominal aorta. The differences in 4D Flow MRI hemodynamic parameters among the three groups were compared using a one-way analysis of variance or the Kruskal-Wallis test. The correlation between 4D Flow MRI hemodynamic parameters and eGFR was analyzed by using the Spearman correlation coefficient. The independent influencing factors that affect eGFR were analyzed by using multivariate linear regression analysis. Results:There were significant differences in abdominal aortic PWV and maximal WSS of Plane_1 and Plane_2 among the three groups ( H=10.38, P=0.006; F=11.16, P<0.001; F=4.75, P=0.011). There were no significant differences in the peak velocity of Plane_1 and Plane_2 among the three groups (both P>0.05). Abdominal aortic PWV was negatively correlated with eGFR ( r s=-0.30, P=0.005). There was a positive correlation between the maximal WSS of Plane_1 and Plane_2 with eGFR ( r s=0.39, P<0.001; r s=0.29, P=0.006). Abdominal aortic PWV and maximal WSS of Plane_1 were independent influencing factors of eGFR (b=-4.32, P=0.018; b=132.23, P=0.004). Conclusions:There is an independent correlation between renal function and abdominal aortic hemodynamic parameters based on 4D Flow MRI in patients with CKD, and abdominal aortic PWV and maximal WSS of Plane_1 were independent influencing factors of eGFR.

Objective To investigate whether O6-methylguanine-DNA methyltransferase(MGMT)interference combined with temozolomide(TMZ)could enhance the therapeutic effect of temozolomide on human drug-resistant melanoma cells A375/TMZ.Methods A375/TMZ cells were randomly divided into 4 groups,control group(normal culture),MGMTsiRNA group(200 nmol·L-1 MGMTsiRNA),experimental group(1 600 μmol·L-1 TMZ)and combined group(transfection of MGMTsiRNA followed by addition of 1 600 μmol·L-1 TMZ).After 24 h of culture,the proliferation of cells in each group was analyzed by cell counting kit-8 method.Western blotting was used to detect the expression levels of poly ADP-ribose polymerase(PARP),cleaved PARP(cleaved-PARP),DNA-dependent protein kinase catalytic subunit(DNA-PKcs)and nuclear factor kappa-B(NF-κB)proteins in the cells.The expression and distribution of NF-κB proteins in the cells were detected by immunofluorescence.Results Cell inhibition rates of control,MGMTsiRNA,experimental and combined groups were 0,(3.45±1.53)％,(51.24±2.73)％and(70.69±4.48)％;the relative expression levels of PARP protein were 0.45±0.08,0.47±0.06,0.33±0.04,0.14±0.03;the relative expression levels of the cleaved-PARP protein were 0.01±0.02、0.01±0.01、0.18±0.03 and 0.36±0.04;the relative expression levels of DNA-PKcs protein were 0.09±0.03,0.07±0.02,0.32±0.02 and 0.39±0.04;the relative expression levels of NF-κB protein were 0.35±0.04,0.36±0.05,0.20±0.02 and 0.15±0.02.Compared with experimental group or control group,the differences of above indexes were all statistically significant(all P＜0.05).Immunofluorescence analysis showed that the average fluorescence intensity of NF-κB in control group,MGMTsiRNA group,experimental group and combined group were(5.26±1.05)％,(7.58±1.18)％,(10.56±1.99)％and(15.47±2.61)％;and compared with the cells in control group and MGMTsiRNA group,combined group showed NF-κB was significantly increased in the nucleus of tumor cells,and the difference was statistically significant(all P＜0.01).Conclusion MGMTsiRNA combined with TMZ further promotes proliferation inhibition and apoptosis of drug-resistant melanoma A375/TMZ cells by TMZ.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To explore the correlation between renal function and abdominal aortic hemodynamic parameters based on four-dimensional flow(4D Flow) MRI in patients with chronic kidney disease (CKD).Methods:A cross-section prospective study was conducted on 73 patients diagnosed with CKD at First People′s Hospital of Changzhou between March 2021 and May 2023, as well as 13 volunteers without kidney injury. According to the estimated glomerular filtration rate (eGFR), the subjects were divided into CKD 1-3 stage group ( n=34), CKD 4-5 stage group ( n=39), and control group ( n=13). All subjects underwent 4D Flow MRI examination of the abdominal aorta, measuring pulse wave velocity (PWV), peak velocity, and maximum wall shear stress (WSS) at the proximal plane (Plane_1) and the higher renal artery opening plane (Plane_2) of the abdominal aorta. The differences in 4D Flow MRI hemodynamic parameters among the three groups were compared using a one-way analysis of variance or the Kruskal-Wallis test. The correlation between 4D Flow MRI hemodynamic parameters and eGFR was analyzed by using the Spearman correlation coefficient. The independent influencing factors that affect eGFR were analyzed by using multivariate linear regression analysis. Results:There were significant differences in abdominal aortic PWV and maximal WSS of Plane_1 and Plane_2 among the three groups ( H=10.38, P=0.006; F=11.16, P<0.001; F=4.75, P=0.011). There were no significant differences in the peak velocity of Plane_1 and Plane_2 among the three groups (both P>0.05). Abdominal aortic PWV was negatively correlated with eGFR ( r s=-0.30, P=0.005). There was a positive correlation between the maximal WSS of Plane_1 and Plane_2 with eGFR ( r s=0.39, P<0.001; r s=0.29, P=0.006). Abdominal aortic PWV and maximal WSS of Plane_1 were independent influencing factors of eGFR (b=-4.32, P=0.018; b=132.23, P=0.004). Conclusions:There is an independent correlation between renal function and abdominal aortic hemodynamic parameters based on 4D Flow MRI in patients with CKD, and abdominal aortic PWV and maximal WSS of Plane_1 were independent influencing factors of eGFR.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.