Structure of natural product-ursolic acid was modified for increasing its antitumor activity. Ursolic acid was acylated, esterified, hydrolized or oxidized to obtain target pentacyclic triterpenoid compounds with different substitutes. Sixteen derivatives of ursolic acid were designed and synthesized including eleven new compounds. Anti-tumor activities of ursolic acid and these derivatives against HeLa, SKOV3 and BGC-823 cells in vitro were investigated by MTT assay. The results indicated that compounds 7a and 8a were found to have stronger cell growth inhibitory than ursolic acid on HeLa cells and SKOV3 cells separately, and are worth to be intensively studied further.

Objective To investigate the situation of the activities of daily living(ADL)for elderly people in Changsha,and analyze the influencing factors. Methods Questionnaire survey on ADL was held in 2239 elderly people(ranging from 60 to 91 years old),and the influencing factors including age,sex,family structure,marital status,education level,occupation,common chronic diseases and medical care consciousness were analyzed. Results Going to the toilet irregularly hadthe highest injury rate in physical self-maintenance viability(18.2%).But in instrumental ADL,the highest injury rate occurred while shopping(26.3%).Advanced age,living alone,losing spouse,sickness and the lack of medical care awareness were the major factors that influenced the ADL of the elderly people. Conclusions The ADL is an important indicator which reflects the health condition of elderly people.Advanced age,living alone,losing spouse,having many chronic diseases and lacking in medical care awareness are risk factors.

Objective:To observe the expression of sirtuin 3 (Sirt3) and mitochondrial damage-associated proteins in lipopolysaccharide (LPS)-induced acute kidney injury mouse model and renal tubular epithelial cells, and to explore the role of Sirt3 in LPS-induced abnormal mitochondrial dynamics in renal tubular epithelial cells.Methods:Eighteen specific pathogen free (SPF) male C57BL/6 mice were randomly assigned to control group, LPS 24 h group and LPS 48 h group. The control group was intraperitoneally injected with physiological saline (0.1 ml/10 g), and LPS 24 h group and LPS 48 h group were intraperitoneally injected with LPS (10 mg/kg) solution. Renal functional indexes of mice were analyzed by automatic biochemical analyzer. The pathological change of the kidney was observed by HE staining, and the expressions of dynamin-related protein-1 (Drp1), optic atrophy type 1 (Opa1) and Sirt3 were evaluated by Western blotting. Expression and distribution of Sirt3 in kidney was assessed by immunohistochemistry. Human renal tubular epithelial cells (HK-2) were exposed to 10 μg/ml LPS for 24 h, and the expression of Drp1, Opa1 and Sirt3 were detected by Western blotting. Cell apoptosis was assessed by Hoechst-33342 staining. After transfection to HK-2 cells with pcDNA3.1-Sirt3 recombinant plasmid, the expressions of Sirt3, Drp1, Opa1 and cell apoptosis were detected by the same methods as above.Results:(1) The levels of blood urea nitrogen and serum creatinine in LPS group were significantly higher than those in control group (both P<0.05), and the pathological changes of kidney were obvious. (2) Compared with the control group, the expression of mitochondrial fission-associated protein Drp1 in renal tissue of LPS group was significantly higher ( P<0.05), and the expression of mitochondrial fusion associated protein Opa1 was significantly lower ( P<0.05). (3) Compared with the control group, the expression of Sirt3 in LPS group was significantly lower ( P<0.05), and immunohistochemistry results showed that Sirt3 was mainly expressed in glomerular vascular endothelial cells and renal tubular epithelial cells. (4) In vitro, LPS stimulation induced increased Drp1 expression in HK-2 cells ( P<0.05), decreased Opa1 and Sirt3 expression (both P<0.05), and increased apoptosis ( P<0.05). (5) LPS-induced mitochondrial dynamics disturbance and apoptosis were alleviated by pcDNA3.1-Sirt3 recombinant plasmid transfection. Conclusions:LPS can induce down-regulation of Sirt3 expression and disturbance of mitochondrial dynamics, and Sirt3 may play a protective role in LPS-induced acute kidney injury by regulating mitochondrial dynamics.

Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.
Autoimmune Diseases/drug therapy* ; Biomarkers ; Glucocorticoids/therapeutic use* ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease/drug therapy*

OBJECTIVE: To investigate the effect of inverse ratio ventilation (IRV) combined with positive end-expiratory pressure (PEEP) in infants undergoing thoracoscopic surgery with single lung ventilation (OLV) for lung cystadenomas. METHODS: A total of 66 infants undergoing thoracoscopic surgery with OLV for lung cystadenomas in our hospital from February, 2018 to February, 2019 were randomized into conventional ventilation groups (group N, =33) and inverse ventilation group (group R, =33). Hemodynamics and respiratory parameters of the infants were recorded and arterial blood gas analysis was performed at 15 min after two lung ventilation (TLV) (T), OLV30 min (T), OLV60 min (T), and 15 min after recovery of TLV (T). Bronchoalveolar lavage fluid was collected before and after surgery to detect the expression level of advanced glycation end product receptor (RAGE). RESULTS: Sixty-three infants were finally included in this study. At T and T, Cdyn, PaO and OI in group R were significantly higher ( < 0.05) and Ppeak, PaCO and PA-aO were significantly lower than those in group N ( < 0.05). There was no significant difference in HR or MAP between the two groups at T and T ( > 0.05). The level of RAGE significantly increased after the surgery in both groups ( < 0.05), and was significantly lower in R group than in N group ( < 0.05). CONCLUSIONS In infants undergoing thoracoscopic surgery with OLV for pulmonary cystadenoma, appropriate IRV combined with PEEP does not affect hemodynamic stability and can increases pulmonary compliance, reduce the peak pressure, and improve oxygenation to provide pulmonary protection.
Cystadenoma ; surgery ; Humans ; Infant ; Lung ; surgery ; One-Lung Ventilation ; Positive-Pressure Respiration ; Thoracoscopy ; Treatment Outcome

OBJECTIVE: To investigate the effect of inverse ratio ventilation (IRV) combined with positive end-expiratory pressure (PEEP) in infants undergoing thoracoscopic surgery with single lung ventilation (OLV) for lung cystadenomas. METHODS: A total of 66 infants undergoing thoracoscopic surgery with OLV for lung cystadenomas in our hospital from February, 2018 to February, 2019 were randomized into conventional ventilation groups (group N, =33) and inverse ventilation group (group R, =33). Hemodynamics and respiratory parameters of the infants were recorded and arterial blood gas analysis was performed at 15 min after two lung ventilation (TLV) (T), OLV30 min (T), OLV60 min (T), and 15 min after recovery of TLV (T). Bronchoalveolar lavage fluid was collected before and after surgery to detect the expression level of advanced glycation end product receptor (RAGE). RESULTS: Sixty-three infants were finally included in this study. At T and T, Cdyn, PaO and OI in group R were significantly higher ( < 0.05) and Ppeak, PaCO and PA-aO were significantly lower than those in group N ( < 0.05). There was no significant difference in HR or MAP between the two groups at T and T ( > 0.05). The level of RAGE significantly increased after the surgery in both groups ( < 0.05), and was significantly lower in R group than in N group ( < 0.05). CONCLUSIONS In infants undergoing thoracoscopic surgery with OLV for pulmonary cystadenoma, appropriate IRV combined with PEEP does not affect hemodynamic stability and can increases pulmonary compliance, reduce the peak pressure, and improve oxygenation to provide pulmonary protection.
Cystadenoma ; therapy ; Humans ; Infant ; Lung ; One-Lung Ventilation ; Positive-Pressure Respiration ; Thoracoscopy

Humans ; Lupus Vasculitis, Central Nervous System/pathology* ; Magnetic Resonance Imaging/methods* ; Diffusion Tensor Imaging/methods* ; Patients ; Lupus Erythematosus, Systemic/pathology* ; Brain/pathology*

Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n = 22) and an exercise group (EX, n = 23). The subjects either adopted LCD (carbohydrate intake < 50 g/day) or performed moderate-to-vigorous exercise (⩾ 30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX ( - 3.56 ± 0.37 kg vs. - 1.24 ± 0.39 kg, P < 0.001), as well as a larger reduction in fat mass ( - 2.10 ± 0.18 kg vs. - 1.25 ± 0.24 kg, P = 0.007) and waist circumference ( - 5.25 ± 0.52 cm vs. - 3.45 ± 0.38 cm, P = 0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.
Adult ; Blood Glucose ; Diet, Carbohydrate-Restricted ; Homeostasis ; Humans ; Pilot Projects ; Weight Loss