To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

Bacillus coagulans can utilize the hydrolyzed carbon source of agricultural waste to produce lactic acid via a homofermentative pathway. However, a significant carbon source metabolic repression effect was observed when the strain metabolized mixed sugars (glucose and xylose), reducing the productivity of lactic acid. In this study, we obtained the fermentation conditions for the simultaneous utilization of the mixed sugars by B. coagulans by changing the ratio of glucose to xylose in the medium. Through transcriptome sequencing, several key genes responsible for xylose utilization were identified. The critical role of xylose isomerase (XylA, EC 5.3.1.5) in the synchronous utilization of glucose/xylose in B. coagulans was investigated via qRT-PCR (quantitative real-time polymerase chain reaction). Subsequently, the heterologous expression and characterization of the XylA-encoding gene (XylA) were conducted. It was determined that the gene encoded a protein composed of 440 amino acid residues. The secondary structure of the encoded protein was predominantly composed of α-helixes and random coils, while the higher structure of the protein was identified as a homotetramer. Then, XylA was cloned and expressed in Escherichia coli BL21(DE3), and the recombinant protein Bc-XlyA was obtained with a molecular weight of approximately 50 kDa. The optimal pH and temperature of Bc-XylA were 8.0 and 60 ℃, respectively, and Mn²⁺, Mg²⁺, and Co²⁺ had positive effects on the activity of Bc-XlyA. The present study provides scientific data on the molecular modification of B. coagulans, offering theoretical support for the efficient utilization of xylose in the strain.
Xylose/metabolism* ; Cloning, Molecular ; Bacillus coagulans/enzymology* ; Aldose-Ketose Isomerases/metabolism* ; Fermentation ; Bacterial Proteins/metabolism* ; Glucose/metabolism*

To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Objective:To investigate the effects and mechanisms of curcumin on insulin resistance in streptozocin-induced diabetic rats.Methods:Diabetic rats were induced by intraperitoneal injection of STZ, then all the rats were randomly divided into diabetes (DM), diabetes+ curcumin (DM+ Cur), and diabetes + buffer control (DM+ NC) groups. Normal SD rats were used as control group (NC). The DM+ Cur group was treated with curcumin, while the DM+ NC group was treated with equal-volume buffer. The test lasted 12 weeks. The blood glucose was detected, and hyperinsulinemic-euglycemic clamp test was performed to estimate peripheral insulin resistance. At the end of the experiments, rats were killed and the total protein and cell membrane protein were extracted from skeletal muscle. The levels of phosphorylated PI3K, phosphorylated AKT, total PI3K, and total AKT were measured by Western blot. The levels of total GLUT4 and GLUT4 of cell membrane were also detected by Western blot, GLUT4 levels in skeletal muscle cell membranes were detected by immunofluorescence.Results:Blood glucose levels of DM+ Cur group were lower than those of DM group [(18.67±1.99 vs 24.38±2.88) mmol/L, P<0.05], and insulin resistance was also improved[the average GIR(14.69±0.29 vs 10.25±0.30) mg·kg -1·min -1, P<0.01]. The phosphorylation levels of PI3K and AKT were increased, and GLUT4 translocation to the cell membrane was increased. Conclusion:By activating the PI3K/AKT pathway, curcumin promotes GLUT4 translocation, increases skeletal muscle glucose uptake, and finally improves insulin resistance.

Objective:To investigate the changes of proopiomelanocortin(POMC) expression in hypothalamus and corresponding metabolism in miR-21 knockout mice.Methods:miR-21 knockout or wild-type C57BL/6J mice were divided into diabetic group and control group, respectively. Diabetic mice model were forged with high-fat diet and low-dose streptozotocin. The changes of body weight and blood glucose in each group were monitored. By the end of the experiment, mice were sacrificed, and POMC protein expression and STAT3 mRNA expression in hypothalamus were detected.Results:There were no significant differences in body weight and blood glucose levels among all groups at baseline( P>0.05). The differences of body weight and blood glucose levels among various groups were compared at 3, 6, 9 and 12 weeks after the model was established. The results showed that body weight of mice in the diabetes group or miR-21 knockout+ diabetes group was higher than that in the control group at each time point( P<0.05). Moreover, there were significant difference in body weight between diabetes group and miR-21 knockout+ diabetes group at 3 and 12 weeks( P<0.05). The blood glucose levels in diabetes group were significantly higher than those in other groups at each time point( P<0.05). The blood glucose level in miR-21 knockout+ diabetes group was lower than that in diabetes group and higher than control group( P<0.05). POMC protein and STAT3 mRNA levels in diabetes group were significantly lower than those in control group, while those in the miR-21 knockout+ diabetes group were higher than those in the diabetes group. Conclusions:The expression of POMC in hypothalamus of miR-21 knockout mice is higher than that of wild-type diabetic mice. miR-21 knockout can decrease blood glucose level and body weight, and improve energy metabolism of diabetic mice.

Objective:To investigate the correlation between urinary 8-oxo-7, 8-dihydroguanosine(8-oxo-Gsn)and physical function in community-dwelling elderly people.Methods:A total of 210 community-dwelling elderly people aged 75 years and over were enrolled in this cross-sectional analysis.According to the scores of short physical performance battery(SPPB), subjects were divided into three groups: the high performance group(summary score 10-12), the intermediate performance group(summary score 7-9)and the low performance group(summary score 0-6). All participants received a comprehensive geriatric assessment.Urinary 8-oxo-dGsn, serum high-sensitivity C-reactive protein(hs-CRP)and white blood cell count were measured.The correlation between urinary 8-oxo-Gsn and physical function was analyzed by using Pearson correlation analysis and the ordered Logistic regression model.Results:The scores of activities of daily living(ADL), instrumental activities of daily living(IADL), grip strength and gait speed were lower in the low performance group than in the other two groups( H=47.002, 110.902, F=11.962, 235.952, all P<0.001). Levels of urinary 8-oxo-Gsn and serum hs-CRP were higher in the low performance group than in the other two groups( F=23.780 and 13.259, both P<0.001). There was no significant difference in levels of urinary 8-oxo-dGsn or white blood cell count between the three groups(both P>0.05). Urinary 8-oxo-Gsn was negatively correlated with gait speed, grip strength and SPPB score( r=-0.559, -0.302 and-0.450, all P<0.001)and was positively correlated with the time of five-times-sit-to-stand test( r=0.290, P<0.001). Adjusting for age, gender and Charlson comorbidity index, the ordered Logistic regression analysis showed that elevated levels of urinary 8-oxo-Gsn( OR=1.38, 95% CI: 1.06-1.77, P<0.05)and hs-CRP( OR=1.23, 95% CI: 1.04-1.48, P<0.05)decreased physical function. Conclusions:Urinary 8-oxo-Gsn is independently associated with the decline of physical function in community-dwelling elderly adults, suggesting that the oxidative stress level is increased in the elderly with poor physical function.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Objective: To explore the clinical features and treatment strategies of tibial plateau fractures sustained with hyperextension varus. Methods: Data of 11 patients of tibial plateau fractures with hyperextension varus treated from January 2008 to November 2017 were retrospectively analyzed. There were 7 males and 4 females with an average age of 41.2 years old (range, 25-67 years). Injuries were caused by falling down in 7 cases, traffic accident in 3 cases, and falling from height in 1 case, respectively. On the basis of Luo's three columns classification in tibial plateau, there were 9 cases of medial column fracture and 2 cases of medial combined with posterior column fracture. Six cases were concomitant with fibular head fracture and 2 cases with the injury of common peroneal nerve. Preoperative magnetic resonance imaging showed that there were anterior cruciate ligament injury in 3 cases, posterior cruciate ligament injury in 4 cases, medial meniscus injury in 5 cases, lateral meniscus injury in 3 cases, medial collateral ligament injury in 6 cases, iliotibial band injury in 2 cases and posterolateral complex injury of the knee joint in 9 cases, respectively. All tibial plateau fractures were treated firstly by open reduction and internal fixation via medial approach of the knee. The medial meniscuses and collateral ligaments were explored, in which of them there were 2 medial meniscuses with the marginal tear been sutured simultaneously. Then the knee joints which were still unstable after the examination of stable tests in 6 cases with posterolateral complex injuries were repaired surgically via lateral approach. Fibular head fractures were fixed with anchor nails or cannulated screws in 6 cases. The ruptured posterior cruciate ligaments in 2 cases were reconstructed with autologous tendon transplantation under endoscopy. Results: All the patients were followed up for an average period of 16.2 months (range, 12-22 months). All fractures were healed in 10-20 weeks with an average time of 16.5 weeks. The range of extension of the affected knee joint in all patients was 0° and the average flexion was 135° (range, 120°-145°) one year after surgery. The average flexion of affected knee in 4 cases which were only treated with the tibial plateau fracture without the mild ligament injuries was 137° (range, 132°-145°) and the average flexion of affected knee in 7 cases who were treated with tibial plateau fracture and severe posterolateral complex included posterior cruciate ligaments completely broken with reconstruction was 132° (range, 120°-140°). According to Rasmussen radiographic evaluation, the average score of all patients was 16.3 (range, 14 to 18) and clinical outcomes were rated with excellent in 10 cases and good in 1. The excellent and good rate was 100% (11/11). The mean of the hospital for special surgery (HSS) score was 86.7 (range, 79-96) and the functional scores were excellent in 9 cases, good in 2 cases thus the excellent and good rate was 100% (11/11). Both varus stress test 30° and dial test were positive in one case considered for the ligament laxity postoperatively who didn’t accept further treatment and the stabilization tests were negative in the other 10 cases. There were no intraoperative complications in all patients such as neurovascular injury. No incision infection, failure of the implants and fracture nonunion occurred postoperatively. Traumatic arthritis of the affected knee occurred one year after surgery in 1 case who had no obvious pain after treated with oral medicine. Conclusion The hyperextension varus injuries of the knee are rare clinically. The posterolateral complex should be evaluated thoroughly for this injury pattern. If it's necessary, the posterolateral structures must be repaired surgically after the tibial plateau fractures are fixed.

Objective To analyze the correlation between urinary albumin/creatinine ratio (ACR) and 24-hour urinary microalbumin (UMA) and evaluate the predictive value of ARC for early diabetic nephropathy.Methods A total of 368 patients with type 2 diabetes mellitus were retrospectively collected.Early diabetic nephropathy was defined as 24h UMA 30～＜300 mg/24h.The correlation between ACR and 24hUMA,and the area under the receiver operating characteristic (ROC) curve of ACR in diagnosis of early diabetic nephropathy were calculated.Gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol were used as adjusting variables to establish univariate and multivariate logistic models of ACR for early diabetic nephropathy,respectively.A regression model was used to evaluate the diagnostic value of ACR for early diabetic nephropathy.Results The correlation between ACR and 24h UMA was 0.658.The area under ROC curve of ACR for early diabetic nephropathy was 0.907 before and 0.933 after adjustments of gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol,respectively.The OR value of ACR of diabetic nephropathy was 2.016 before and 2.762 after same adjustments.The calibration of Hosmer-Lemeshow chi-square test evaluation model was 19.362 before (P=0.13) and 14.928 after adjustments (P=0.061).Conclusion ACR is a better predictor for early diabetic nephropathy although its value is influenced by gender,age,course of disease,blood sugar,lipid,and blood pressure.