Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

BACKGROUND:Hyperhomocysteinemia is closely related to the function of islet β cells,but its specific molecular mechanism is not fully understood. OBJECTIVE:To investigate the role of N6 methyltransferase-like 3(METTL3)in homocysteine(Hcy)-induced autophagy of mouse islet β cells. METHODS:The 3rd and 4th generation mouse islet β cells were taken for the experiment.(1)Cell modeling and grouping:cells in control group were not treated with Hcy,while those in homocysteine group were treated with 100 μmol/L Hcy for 48 hours.(2)The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000.Three different interfering fragments were designed,and the one with the best interfering efficiency was verified and screened by PCR.(3)After transfection,the cells were divided into control group,Hcy group,Ad-NC(negative control)+Hcy group,Ad-METTL3+Hcy group,si-NC(negative control)+Hcy group and si-METTL3+Hcy group.(4)qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3Ⅱ/Ⅰ and p62 in cells.Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells.Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION:Compared with the control group,the expression level of LC3Ⅱ/Ⅰ was increased(P＜0.05),the expression of p62 was significantly reduced(P＜0.05),and the insulin secretion capacity was significantly decreased(P＜0.05)in the Hcy group.Compared with the control group,the protein and mRNA levels of METTL3 were reduced in the Hcy group(P＜0.05).After METTL3 silencing in islet β cells,Hcy further upregulated the expression of LC3Ⅱ/Ⅰ(P＜0.05),significantly dowregulated the expression of p62(P＜0.05),and increased the insulin level(P＜0.05).After overexpression of METTL3,Hcy significantly decreased the LC3Ⅱ/Ⅰ expression and increased the p62 expression in islet β cells(P＜0.05).To conclude,METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion.

AIM:To investigate the role of specific long noncoding RNA SLC25a6(lncSLC25a6)in homocys-teine(Hcy)-induced cuproptosis in cardiomyocytes.METHODS:Rat cardiomyocytes were cultured in vitro and divided into control group and Hcy group.After 48 h of intervention,the expression levels of cuproptosis-related proteins,ferre-doxin 1(FDX1)and heat shock protein 70(HSP70),were detected by Western blot and immunofluorescence staining.The oxidative stress state of cardiomyocytes was assessed using fluorescence staining,and the intracellular Cu2+levels were measured using a copper ion assay kit.Furthermore,the impact of Hcy on the expression of cuproptosis-related proteins in cardiomyocytes was analyzed following overexpression of lncSLC25a6.RESULTS:Compared with the control group,80 μmol/L Hcy significantly accelerated cardiomyocyte damage,with a notable underexpression of lncSLC25a6(P<0.05).Western blot results indicated that,compared with the control group,the expression level of FDX1 in the Hcy intervention group was significantly reduced(P<0.05),while the expression level of HSP70 was significantly elevated(P<0.05),and the expression level of copper ions in cardiomyocytes of the Hcy group was increased(P<0.05).Immunofluorescence staining showed a significant reduction in FDX1 fluorescence intensity and a significant increase in HSP70 fluorescence in-tensity in the Hcy group.Further overexpression of lncSLC25a6 significantly mitigated Hcy-induced cuproptosis in cardio-myocytes,resulting in elevated expression of FDX1 and reduced expression of HSP70(P<0.05).Pearson correlation analysis demonstrated that the expression level of lncSLC25a6 was negatively correlated with FDX1 protein expression(r=-0.676,P=0.046)and positively correlated with HSP70 expression(r=0.680,P=0.044).CONCLUSION:lnc-SLC25a6 significantly mitigates Hcy-induced cuproptosis in cardiomyocytes,positioning it as a potential therapeutic target for managing Hcy-induced cardiac injury.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

[摘 要] 目的：探讨miR-203a-3p对胰腺癌BxPC-3细胞增殖、迁移和侵袭能力的影响。方法：运用癌症基因组图谱（TCGA）数据库筛选胰腺癌组织和癌旁组织中差异表达的miRNA，分析miRNA高表达与低表达时胰腺癌患者的生存率和临床分期；利用TarBase数据库分析miRNA与癌症相关的GO功能与KEGG通路，利用DIANA Tools、miRDB和TargetScan网站预测miR-203a-3p的靶基因。将miR-203a-3p mimic及NC mimic、miR-203a-3p inhibitor及NC inhibitor转染至BxPC-3细胞，用qPCR法检测胰腺癌细胞和胰腺正常上皮细胞HPNE中miR-203a-3p、miR-192-5p和miR-451a表达水平，以CCK-8法、Transwell小室法和克隆形成实验分别检测BxPC-3细胞的增殖、迁移、侵袭和集落形成能力。结果：通过TCGA数据库筛选出18个胰腺癌组织中差异表达的miRNA，其中miR-203a-3p、miR-192-5p、miR-451a具有物种保守性，且其与胰腺癌临床癌症分期、细胞周期和患者生存率相关（均P<0.05）；生物信息学网站预测显示miR-203a-3p的候选靶基因是PPM1A，PPM1A与多基因存在相互作用。miR-203a-3p、miR-192-5p和miR-451a在BxPC-3和Aspc-1细胞中均高表达（均P<0.01）。miR-203a-3p mimic组BxPC-3细胞中miR-203a-3p表达水平以及细胞增殖、迁移和侵袭能力均显著提高（均P<0.01）；miR-203a-3p inhibitor组细胞中miR-203a-3p表达水平以及细胞增殖、迁移和侵袭能力均显著降低（均P<0.01）。结论：miR-203a-3p在胰腺癌组织及细胞中均高表达，其表达与患者生存和临床分期相关，可调控BxPC-3细胞的增殖、迁移和侵袭能力。

Objective:To investigate the contents of soil metal elements in the plague high incidence area and resting area in the plague natural foci of Qingnan region in Qinghai Province, and to compare and analyze the differences of the contents of soil metal elements between the two areas.Methods:A total of 69 soil samples were collected from 11 sites in the plague high incidence area (Yushu Prefecture) and resting area (Guoluo Prefecture) in Qingnan region, including 39 samples from high incidence area and 30 samples from resting area. The contents of 12 soil metal elements, such as iron (Fe), magnesium (Mg), calcium (Ca), barium (Ba), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), rubidium (Rb), titanium (Ti), vanadium (V) and zinc (Zn), were measured by X-ray fluorescence spectrometry and SPSS 20.0 software was used for Spearman correlation and other statistical analysis.Results:The contents of Fe and Ca in the soil of the plague natural foci of Qingnan region were relatively high. The contents of 12 soil metal elements in the high incidence area were significantly higher than those in the resting area ( P < 0.01 or < 0.05). There were statistical significant differences in the contents of Mg, Ca, Ba, Mn, Pb and Zn in the soil among the sample plots of the plague high incidence area ( P < 0.01 or < 0.05). There were statistical significant differences in the contents of Fe, Mg, Ca, Rb and Ti in the soil among the sample plots of the plague resting area ( P < 0.05 or < 0.01). Except for Mg and Ca, Fe was positively correlated with other metal elements in the high incidence area and resting area ( P < 0.01 or < 0.05), and Fe was strongly positively correlated with Rb, Ti and V ( r = 0.780 - 0.838). Mg was only positively correlated with Ca in the high incidence area and resting area ( P < 0.01). Ca was negatively correlated with Mn, Pb, Rb, Ti, V and Zn in the high incidence area, and with Rb and Zn in the resting area ( P < 0.01 or < 0.05). The rest of the metal elements were mostly positively correlated in the high incidence area and resting area. Conclusions:The contents of Fe and Ca are rich in the plague natural foci of Qingnan region in Qinghai Province. There are correlations among most soil metal elements in the high incidence area and resting area. The correlation between the contents of soil metal elements in the plague natural foci and the epidemic of plague is worth further exploring.

Objective To explore the effect of transitional care model on health recovery in discharged elderly patients with angiocardiopathy.Methods A group of transitional care of geriatric department was formed by physicians and nurses of geriatric department, physicians and therapists of rehabilitation department and so on. A total of 81 discharged patients with angiocardiopathy of geriatric department in the Second People's Hospital of Nantong were selected as research group from July 2015 to February 2016 using purposive sampling. They accepted transitional care. A total of 85 elderly patients with angiocardiopathy were recruited as control between December 2015 to June 2016 with routine health education. The effect and the patients' satisfaction were compared between two groups.Results The compliance rate of medication of patients was 93.6% in research group and 65.8% in control group in the second week after leaving hospital with a significant difference (χ2=20.447,P<0.05). There was a statistically significant difference in satisfaction between research group [(95.21±1.98)%] and control group [(88.34±1.84)%] (t=32.7470,P<0.05).Conclusions The transitional care can improve the medication compliance in discharged elderly patients with angiocardiopathy, help them build up health lifestyle and improve the quality of life of patients.

Objective To Explore the therapy of elderly patients with hypoproliferative acute myeloid leukemia.Methods Twenty-six elderly patients with hypoproliferative acute myeloid leukemia had received induction of CAG regimen and 15 cases were treated intensive chemotherapy after complete remission,then if achieving complete remission had received subsequent intensive chemotherapy: stand or reduce AA, DA or HA regimen.Results In 26 cases patients who received CAG regimen,the complete remission rate, partial remis sionrat and the totle total effective rate were 53.85％ (14/26), 19.23％ (5/26) and 73.08％ (19/26), respectively.Accordance with response to CAG regimen and the therapy after complete remission, 26 patients were divided into 3 groups:intensive chemotherapy after complete remission(CR1), non-intensive chemotherapy after complete remission(CR2) and non-remission(NR, including partial remission patients).The median overall survival of CR1 ,CR2 and NR were 13.5 months, 8.2 months, and 4.5 months, respectively.There was higher median overall survival of CR1 group than CR2 and NR groups (P =0.041,0.001, respectively).There was higher OS of CR2 group than NR group (P =0.064).No serious bleeding events were found in chemotherapy.Conclusion CAG regimen was an effective and little adverse effect regimen for the treatment of elderly H-AML,and with well tolerance in patients.Advisable intensive chemotherapy can prolong the patient's survival time after complete remission.