Aralia taibaiensi, widely distributed in western China, particularly in the Qinba Mountains, has been utilized as a folk medicine for treating diabetes, gastropathy, rheumatism, and cardiovascular diseases. Saponins from A. taibaiensis (sAT) have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion (I/R). However, the underlying mechanisms remain unclear. In vivo, middle cerebral artery occlusion/reperfusion (MCAO/R) induced inflammatory infiltration, neuronal injury, cell apoptosis, mitochondrial dysfunction, and oxidative stress in the ischaemic penumbra, which were effectively mitigated by sAT. sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors (ARs) both in vivo and in vitro. (Ala13)-Apelin-13 (F13A) and small interfering RNA (siRNA) abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/protein kinase B (Akt). Furthermore, sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase (P38 MAPK)/activating transcription factor 4 (ATF4) and upregulating hypoxia-inducible factor-1α (HIF-1α). Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a, thereby suppressing oxidative stress and mitochondrial dysfunction.
Animals ; Reperfusion Injury/prevention & control* ; Aralia/chemistry* ; Saponins/administration & dosage* ; AMP-Activated Protein Kinases/genetics* ; Male ; Apelin/genetics* ; Signal Transduction/drug effects* ; Neuroprotective Agents/administration & dosage* ; Brain Ischemia/genetics* ; Rats, Sprague-Dawley ; Rats ; Oxidative Stress/drug effects* ; Apelin Receptors/genetics* ; Humans ; Apoptosis/drug effects* ; Mice

Objective To investigate the correlation between coagulation system biomarkers and bone mineral den-sity(BMD)in patients with spinal degenerative diseases.Methods A total of 251 patients who underwent surgical treatment for spinal degenerative diseases at the Department of Spinal Surgery,Beijing Jishuitan Hospital,from March to October 2019,were enrolled in this study.These patients had both BMD data and coag-ulation system test results available.The distribution of coagulation indicators,including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),and thrombin time(TT),was analyzed across different gender and BMD groups.Results A retrospective analysis of laboratory coagulation indicators revealed that in male patients,only fibrinogen levels were significantly increased with the reduction of BMD(P＜0.05).PT and APTT did't show significant differences in female patients across BMD groups,but fibrinogen levels increased with the decrease in BMD(P＜0.05).Patients were classified into osteoporosis and non-osteoporosis groups based on their BMD results.Pearson correlation analysis was performed between the binary variable of BMD grouping and patients'coagulation indicators.The results showed a significant negative correlation between BMD grouping and fi-brinogen levels in both genders(P＜0.05).Conclusions Fibrinogen level in patients with spinal degenerative dis-eases significantly increases as BMD decreases,suggesting that fibrinogen may serve as a predictive biomarker for BMD stratification in these patients.

Obesity has become a major global public health issue,and the situation in China is also becoming increasingly severe.Adipose tissue is categorized into white adipose tissue(WAT)and brown adipose tissue(BAT),which regulates metabolic homeostasis by secreting various adipokines.Mitochondria,as the core organelles of energy metabolism,its dysfunction are closely related to obesity.In the state of obesity,mitochondrial dynamics imbalance,oxidative stress,and metabolic dysfunction can all lead to energy metabolism disorders and adipose tissue dysfunction.Moreover,mitochondrial dysfunction not only affects adipose tissue but also extends to multiple organs such as muscles and livers,thereby exacerbating obesity and related metabolic diseases.In recent years,although numerous therapeutic strategies targeting mitochondrial dysfunction have been actively explored,their clinical translation faces challenges.This review explores the association between mitochondrial dysfunction in adipose tissue and obesity,analyses its mechanism and existing treatment strategies,aiming to provide a new perspective for the diagnosis and treatment of obesity.

BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods. METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median. The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran's Q,MR-Egger regression,and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran's Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95％ confidence interval (CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05,95％ CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04,95％ CI:-0.07,-0.01,P=0.005;β=-0.04,95％ CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04,95％ CI:0.01,0.08,P=0.012;β=0.04,95％ CI:0.00,0.07,P=0.039),and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10,95％ CI:-0.16,-0.03,P=0.002). When heel bone mineral density was used as an outcome,there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04,95％ CI:-0.07,-0.01,P=0.016),and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05,95％ CI:0.01,0.08,P=0.007;β=0.05,95％ CI:0.01,0.08,P=0.004). To ensure the robustness of the results,meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count,there was a 5％ reduction in the risk of decreased bone mineral density (OR=0.95,95％ CI:0.94,0.97,P<0.001);whereas for every standard deviation increase in hemoglobin concentration and hematocrit,there was a 4％ reduction in the risk of decreased bone density (OR=1.04,95％ CI:1.03,1.06,P<0.001). In conclusion,increased white blood cell count in peripheral blood is a risk factor for bone mineral density;whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density.

BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods. METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median. The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran's Q,MR-Egger regression,and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran's Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95％ confidence interval (CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05,95％ CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04,95％ CI:-0.07,-0.01,P=0.005;β=-0.04,95％ CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04,95％ CI:0.01,0.08,P=0.012;β=0.04,95％ CI:0.00,0.07,P=0.039),and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10,95％ CI:-0.16,-0.03,P=0.002). When heel bone mineral density was used as an outcome,there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04,95％ CI:-0.07,-0.01,P=0.016),and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05,95％ CI:0.01,0.08,P=0.007;β=0.05,95％ CI:0.01,0.08,P=0.004). To ensure the robustness of the results,meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count,there was a 5％ reduction in the risk of decreased bone mineral density (OR=0.95,95％ CI:0.94,0.97,P<0.001);whereas for every standard deviation increase in hemoglobin concentration and hematocrit,there was a 4％ reduction in the risk of decreased bone density (OR=1.04,95％ CI:1.03,1.06,P<0.001). In conclusion,increased white blood cell count in peripheral blood is a risk factor for bone mineral density;whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density.

Objective To investigate the expression of serum CC chemokine ligand 2(CCL2),CX3C chemokine ligand 1(CX3CL1)and CXC chemokine ligand 10(CXCL10)in postmenopausal osteoporosis(PMOP)patients and the value of combination with fracture risk assessment tool(FRAX)in predicting fracture occurrence.Methods A total of 120 patients with PMOP admitted to Hainan West Central Hospital from January 2022 to June 2023 were selected,and they were divided into fracture group(n=52)and non-fracture group(n=68).According to the FRAX score examination,they were divided into a high-risk fracture group(n=73)and a low-risk fracture group(n=47).The levels of serum CCL2,CX3CL1 and CXCL10 in each group were compared.Multivariate Logistic regression was used to analyze the fracture risk factors in PMOP patients.ROC curve was drawn to analyze the value of CCL2,CX3CL1 and CXCL10 combined with FRAX score in predicting fracture of PMOP.Results The levels of serum CCL2(134.98±32.24 pg/ml),CX3CL1(186.25±41.60 pg/ml)and CXCL10(223.47±56.43 pg/ml)in the fracture group were higher than those in the non-fracture group(82.26±17.30 pg/ml,105.23±23.78 pg/ml,151.47±43.14 pg/ml),and the differences were statistically significant(t=11.503,13.452,7.923,all P＜0.001).The levels of serum CCL2(119.70±37.56 pg/ml),CX3CL1(161.43±53.79 pg/ml)and CXCL10(204.06±61.41pg/ml)in the high-risk group for fractures were higher than those in the low-risk group(82.43±17.23 pg/ml,107.55±24.75 pg/ml,149.45±42.50pg/ml),and the differences were statistically significant(t=6.377,6.436,5.327,all P＜0.001).Multivariate Logistic regression analysis showed that elevated levels of serum CCL2,CX3CL1 and CXCL10 were risk factors for fractures in PMOP patients.The ROC curve showed that the combination of CCL2,CX3CL1 and CXCL10 combined with FRAX scores predicted the highest AUC(95％CI)for PMOP fractures[0.951(0.892～0.993)],with sensitivity and specificity of 98.2％and 85.6％,respectively.Conclusion The increased levels of serum CCL2,CX3CL1 and CXCL10 are risk factors for fracture in PMOP patients,and the combination with FRAX score has a good predictive value for fracture.

Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.

Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.

Objective:To investigate the diagnostic value of serum CircRNA_0048211 expression level in postmenopausal osteoporosis (PMOP) and its correlation with bone-specific alkaline phosphatase (BALP), osteopontin (OPN), procollagen type I N-terminal propeptide (PINP) and β-crosslaps (β-CTX). Methods:Data of postmenopausal women who underwent physical examination in our hospital from January 2019 to December 2021 were collected. All subjects were measured bone mineral density (BMD) by dual-energy X-ray absorptiometry and divided into PMOP group, decreased bone mass group and normal bone mass group according to BMD level. The serum CircRNA_0048211, BALP, OPN, PINP and β-CTX levels were compared in each group. Binary logistic regression was used to analyze the risk factors of PMOP, the receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of CircRNA_0048211, BALP, OPN, PINP and β-CTX on PMOP. The correlation between CircRNA_0048211 expression level and BALP, OPN, PINP and β-CTX was analyzed by Pearson correlation analysis. Results:A total of 218 patients were included in this study. Age is 60.52±6.83 years (range, 47-76 years), body mass index is 24.27±2.28 kg/m 2 (range, 22.18-25.73 kg/m 2) and menopausal time is 10.16±4.25 years (range, 2.30-21.80 years). There were 40 cases in PMOP group, 97 cases in osteopenia group and 81 cases in normal bone mass group. The serum CircRNA_ 0048211, BALP, OPN, PINP and β-CTX was significantly different between PMOP group, osteopenia group and normal group ( F=21.15, P<0.001; F=12.52, P<0.001; F=17.86, P<0.001; F=14.32, P<0.001; F=15.52, P<0.001). The serum CircRNA_0048211 level in PMOP group (0.37±0.08) were significantly lower than that of osteopenia group (1.05±0.46) and normal bone mass group (1.73±0.81), the difference was statistically significant ( P<0.05). The levels of BALP (28.42±7.35 μg/L), OPN (17.28±7.30 ng/ml), PINP (58.40±14.37 ng/ml) and β-CTX (1.52±0.28 μg/L) in PMOP group were significantly higher than those in osteopenia group (22.61±5.93 μg/L, 11.95±5.64 ng/ml, 49.16±11.24 ng/ml, 0.81±0.17 μg/L) and normal bone mass group (16.30±4.18 μg/L, 7.62±3.25 ng/ml, 35.48±7.12 ng/ml, 0.37±0.10 μg/L), the difference was statistically significant ( P<0.05). Binary logistic regression analysis showed that decreased CircRNA_0048211 expression level [ OR=3.53, 95% CI (2.73, 10.32)] was a risk factor for the occurrence of PMOP ( P<0.001). ROC curve showed that CircRNA_0048211≤0.76 has a diagnostic significance on PMOP, and its combination of BALP, OPN, PINP and β-CTX has the highest AUC [0.95, 95% CI (0.89, 1.00)] in diagnosing PMOP. Correlation analysis showed that CircRNA_0048211 expression level were negatively correlated with BALP, OPN, PINP and β-CTX ( r=-0.46, P<0.001; r=-0.80, P<0.001; r=-0.81, P<0.001; r=-0.69, P<0.001). Conclusion:The CircRNA_0048211 showed low expression in PMOP, which was negatively correlated with BALP, OPN, PINP and β-CTX. The combination of these five factors has certain clinical value in the diagnosis of PMOP.

Objective:To evaluate the effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.Methods:One hundred and sixty elderly hypertensive patients of both sexes, aged 60-80 yr, with body mass index of 19-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection for gastrointestinal tumor under general anesthesia, were divided into 2 groups ( n=80 each) using a random number table method: standardized blood pressure management group (group S) and individualized blood pressure management group (group I). Combined intravenous-inhalational anesthesia was performed, and BIS values were maintained at 40-60 and heart rate at 50-100 times/min during surgery in both groups. In group S, intraoperative systolic blood pressure was maintained above 90 mmHg with a decrease of less than 30% of the baseline value, while intraoperative fluctuation of systolic blood pressure was maintained less than 10% of the baseline value in group I. The use of vasoactive agents, numerical rating scale scores within 3 days after operation, and length of hospital stay were recorded. Postoperative delirium was evaluated by Confusion Assessment Method within 5 days after surgery. Results:Compared with group S, the intraoperative usage rate of norepinephrine was significantly increased, the incidence of postoperative delirium was reduced( P<0.05), and no significant change was found in the numerical rating scale scores and length of hospital stay in group I ( P>0.05). Conclusions:Individualized blood pressure management can reduce the development of postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.