Objective:To investigate the mechanism by which baicalein alleviates osteoarthritis by regulating Sirtuin (Sirt) to inhibit the senescence of fibroblast-like synoviocytes (FLS).Methods:FLS were extracted from synovium of non-osteoarthritis patients (3 patients) and osteoarthritis patients (3 patients), and assessed the senescence of FLS in osteoarthritis patients by Western blot, β-galactosidase staining and immunofluorescence, and examined the changing levels of Sirt family proteins and mRNAs in FLS. The relative expression level of Sirt1 in FLS was knocked down by transfection with Sirt1 siRNA, and the antioxidative capacity and senescence degree of FLS were analyzed. Chondrocytes were co-cultured with FLS and functional changes in chondrocytes were detected by Western blot. After inducing FLS senescence with bleomycin (BLM), different concentrations of baicalein were administered to detect the expression levels of Sirt1, p16, and p21 proteins and intracellular reactive oxygen species (ROS). The expression level of Sirt1 in FLS was knocked down, and BLM and baicalein treatments were applied. The relative expression levels of Sirt1 and ROS were detected using Western blot and ROS assays. After BLM-induced FLS senescence, baicalein and Compound C were added. The relative expression levels of phosphorylated AMP-activated protein kinase (pAMPK), nuclear factor erythroid 2-related factor 2 (NRF2), p16, p21, and ROS were detected by Western blot and ROS assays.Results:The relative expression of p16 and p21 in FLS in the osteoarthritic group were 3.66±0.38 and 3.55±0.34, which were higher than those in non-osteoarthritis group 1.00±0.07 and 1.00±0.09 ( t=11.860, P<0.001; t=12.520, P<0.001). The relative expression levels of Sirt1 and Sirt6 in FLS in the osteoarthritis group were 0.30±0.04 and 0.16±0.01, which were smaller than those in the non-osteoarthritis group 1.00 ± 0.03 and 1.00±0.04 ( t=23.840, P<0.001; t=34.130, P<0.001). After baicalein treatment, the relative expression of ROS was 2.58±0.28, 1.65±0.14 and 1.00±0.24 in the BLM, BLM+Bai and control groups, respectively, with statistically significant differences between the groups ( F=35.700, P<0.001), which was greater in the BLM and BLM+Bai than in the control group, and lower in the BLM+Bai than in the BLM group ( P<0.05). The relative expression of pAMPK and NRF2 was 0.28±0.02 and 0.38±0.09 after Compound C+Baicalein treatment, which was lower than that of 0.56±0.07 and 0.60±0.08 in the BLM+Bai group ( P<0.05). The relative expression of ROS increased from 1.75±0.16 to 3.45±0.12 ( P<0.001). The proportion of positivity in the BLM+Bai+Compound C, BLM+Bai and control groups was 47.30%±4.29%, 18.18%±3.89% and 7.70%±3.53% ( F=109.700, P<0.001), respectively, with the BLM+Bai+Compound C group being higher than that in the BLM+Bai group ( P<0.05). Conclusion:The downregulation of Sirt1 expression in patients with osteoarthritis leads to FLS senescence and accelerates the progression of osteoarthritis. Baicalein can inhibit FLS senescence by activating Sirt1/AMPK/NRF2 pathway, which may delay the progression of osteoarthritis and improve the function of chondrocytes.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Two patients (patient 1, a 49-year-old female; patient 2, a 51-year-old female) took Anshen Bunao liquid 10 ml twice daily orally by themselves because of poor sleep. None of the 2 patients had concomitant medications. Patient 1 and patient 2 developed fatigue and poor appetite after 7 and 10 days of Anshen Bunao liquid treatment, respectively. Laboratory tests showed that alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were 1 147 U/L, 1 271 U/L, 215 U/L and 805 U/L, 333 U/L, 227 U/L, respectively. Then Anshen Bunao liquid was stopped and hepatoprotective therapy was given. Seven days later, symptoms of fatigue and poor appetite in the 2 patients were improved, amd laboratory tests showed that the levels of ALT, AST, ALP decreased to 222 U/L, 396 U/L, 122 U/L and 85 U/L, 23 U/L, 129 U/L, respectively. Patient 1 took Anshen Bunao liquid again. Two days later, she developed abdominal discomfort with vomiting, ALT was 409 U/L, and AST was 339 U/L. After stopping the drug and giving liver-protective treatments for nearly 4 months, ALT was 32 U/L, AST was 22 U/L, and ALP was 89 U/L. Patient 2 did not take the drug again. Re-examination after 138 days after discharge, ALT was 39 U/L, AST was 28 U/L, and ALP was 130 U/L.

Two patients (patient 1, a 49-year-old female; patient 2, a 51-year-old female) took Anshen Bunao liquid 10 ml twice daily orally by themselves because of poor sleep. None of the 2 patients had concomitant medications. Patient 1 and patient 2 developed fatigue and poor appetite after 7 and 10 days of Anshen Bunao liquid treatment, respectively. Laboratory tests showed that alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were 1 147 U/L, 1 271 U/L, 215 U/L and 805 U/L, 333 U/L, 227 U/L, respectively. Then Anshen Bunao liquid was stopped and hepatoprotective therapy was given. Seven days later, symptoms of fatigue and poor appetite in the 2 patients were improved, amd laboratory tests showed that the levels of ALT, AST, ALP decreased to 222 U/L, 396 U/L, 122 U/L and 85 U/L, 23 U/L, 129 U/L, respectively. Patient 1 took Anshen Bunao liquid again. Two days later, she developed abdominal discomfort with vomiting, ALT was 409 U/L, and AST was 339 U/L. After stopping the drug and giving liver-protective treatments for nearly 4 months, ALT was 32 U/L, AST was 22 U/L, and ALP was 89 U/L. Patient 2 did not take the drug again. Re-examination after 138 days after discharge, ALT was 39 U/L, AST was 28 U/L, and ALP was 130 U/L.

Linezolid is an oxazolidinone antibacterial agent used in infections caused by gram-positive cocci such as methicillin-resistant staphylococcus aureus, penicillin-resistant pneumococcus and vancomycin-resistant enterococcus. Lactic acidosis is one of the adverse reactions of linezolid. The risk factors of lactic acidosis caused by linezolid are long-term exposure, liver dysfunction, renal dysfunction, mitochondrial DNA A2706G polymorphism, combined use of drugs affecting mitochondrial function, etc. The symptoms of lactic acidosis caused by linezolid are nausea, vomiting, drowsiness, shortness of breath, tachycardia, and hypotension, etc., which can be identified early by close monitoring of laboratory indicators such as blood lactic acid, pH, and blood drug concentration. The mechanism of lactic acidosis induced by linezolid may be related to mitochondrial toxicity. The lactic acidosis of linezolid can be caused by reducing drug dose, stopping drug or even in vitro renal replacement therapy, and strengthening symptomatic support therapy if necessary. This review is intended to provide ideas for the clinical prevention and treatment of lactate acidosis caused by linezolid.

Objective To explore the effect and molecular mechanism of CC chemokine ligand 2 (CCL2) on epithelial-mesenchymal transition in human breast cancer cells.Methods Breast cancer Michigan cancer foundation-7 (MCF-7) cells were treated with 50 ng/ml CCL2.The abilities of invasion were detected by Transwell assay.The expression of epithelial-mesenchymal transition (EMT)-associated markers,E-cadherin and vimentin were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).The expressions of Snail,protein kinase B (AKT),phosphorylated protein kinase B (p-AKT),phosphorylated glycogen synthase kinase 3β (p-GSK3β3) and GSK3β were detected by Western blot.Snail nuclear localization was detected by immunoflurescence staining.Results We found that CCL2 treatment could induce morphological alteration of MCF-7 cells from epithelial morphology to mesenchymal morphology.CCL2 significantly increased the migration of MCF-7 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More important,treatment of CCL2 significantly increased the expression of Snail,and promoted the nuclear localization of Snail.Knockdown of Snail significantly reverse the effects of CCL2 on the EMT in MCF-7 cells.Moreover,treatment of CCL2 significantly increased the phosphorylation levels of p-AKT and p-GSK3β,and AKT inhibitor LY294002 significantly inhibited CCL2-induced Snail and p-GSK3β expression.Conclusion CCL2 might induce EMT in MCF-7 cells,by which mechanism is related to activate AKT/GSK3β Snail pathway.

Objective To evaluate outpatient and inpatient medical services of hospitals in various regions of the whole country in 2009.Methods RSR was applied to perform the statistical analysis.Results The hospital outpatient and inpatient medical services in 31 provinces and municipalities (municipalities and autonomous regions) were divided into four grades.The hospital outpatient and inpatient medical services were excellent in Guangdong, Yunnan, Hebei, Jiangsu, Hubei, Shandong, Henan, Hunan, good in Guangxi, Liaoning, Heilongjiang, Shaanxi, Jiangxi, Anhui, Guizhou, Sichuan, Zhejiang, fair in Qinghai, Beijing, Fujian, Shanxi, Inner Mongolia, Gansu, Chongqing and Xinjiang,and poor in Hainan, Tianjin, Ningxia, Tibet, Shanghai, Jilin.Conclusion RSR is suit-able for the comprehensive evaluation of any material, scientifically reflecting the outpatient and inpatient medical services of hospitals in various regions of the whole country.

Objective To summarize clinical observation and nursing of 36 patients with gestational diabetes complicated with hypertension during caesarean perioperation.Methods A to-tal of 36 patients with gestational diabetes complicated with hypertension used holistic nursing and additionally strengthened maternal and neonatal illness observation,blood glucose,blood pressure management,prevention of infection and venous thrombosis and health care and education measures based on the conventional nursing.Results All the 36 patients successfully completed the cesarean section operation without maternal and neonatal mortality,puerperae and children were smooth dis-charged without complications.Conclusion Comprehensive nursing measures,careful clinical ob-servation and safe,effective nursing measures ensure the safety of patients with gestational diabetes complicated with hypertension.

Objective To summarize clinical observation and nursing of 36 patients with gestational diabetes complicated with hypertension during caesarean perioperation.Methods A to-tal of 36 patients with gestational diabetes complicated with hypertension used holistic nursing and additionally strengthened maternal and neonatal illness observation,blood glucose,blood pressure management,prevention of infection and venous thrombosis and health care and education measures based on the conventional nursing.Results All the 36 patients successfully completed the cesarean section operation without maternal and neonatal mortality,puerperae and children were smooth dis-charged without complications.Conclusion Comprehensive nursing measures,careful clinical ob-servation and safe,effective nursing measures ensure the safety of patients with gestational diabetes complicated with hypertension.

Objective To explore the status and risk factors of the dyslipidemia among health examination population of Lanzhou for providing the intervention measures .Methods According to the stratified cluster random sampling method ,4 505 health exami-nation individuals were recruited for the study from 5 hospitals in the Lanzhou region through questionnaire ,biochemical analysis . Results Prevalence of dyslipidemia of the population was 45 .79% ,high TG was the main type .The level of serum TC ,TG ,HDL-C and LDL-C were (5 .27 ± 1 .08) ,(1 .74 ± 1 .38) ,(1 .41 ± 0 .43) and (2 .83 ± 0 .82)mmol/L .The prevalence was 53 .49% in male , and 34 .93% in female .The prevalence was higher among the group of 35- <45 years old for male and 55- <65 years old for fe-male .The level of HDL-C was low among young people .There was aggregation of risk factors among the participants with dyslipi-demia .Non-conditional logistic regression analysis showed that the risk factors were age (OR=1 .701) ,overweight (OR=5 .560) , abdominal obesity(OR=2 .398) ,smoking(OR=0 .545) ,intake of greasy diet(OR=5 .313) ,sleep quality(OR=2 .005) and diastolic blood pressure(OR=3 .061) .Conclusion Lipid disorders becomes a serious problem in the health examination population ,measures such as rational diet ,weight control ,sleep improvement ,pressure control and quiting smoking must be taken .