AIM:To evaluate the efficacy,safety,and economy of camrelizumab(CAM)combined with platinum-containing chemotherapy(CT)for the first-line treatment of locally advanced/meta-static non-small cell lung cancer(NSCLC).METH-ODS:Chinese and English databases such as Pubmed,the Cochrane Library,China Knowledge Network,Wanfang Data,and other related web-sites were systematically searched.After literature screening,quality assessment,and data extraction of the literature according to the inclusion and ex-clusion criteria,two researchers conducted a rapid health technology assessment(HTA).RESULTS:A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included.In terms of effectiveness,compared to docetaxel che-motherapy,CAM+CT significantly prolonged the overall survival(OS),progression-free survival(PFS),and improved the objective remission rate(ORR)of mutation-negative patients with locally ad-vanced/metastatic NSCLC.Compared with CT and pembrolizumab(PEM),CAM+CT significantly pro-longed the PFS,and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC.Subgroup analysis showed that CAM+CT significantly prolonged PFS in patients with PD-L1 ≥1％and PD-L1 ≥ 50％compared with CT.Compared with CT,CAM+CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Compared with sintilimab(SIN),CAM+CT significantly pro-longed the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Sub-group analysis showed that CAM+CT significantly prolonged OS in patients with PD-L1＜1％com-pared with CT.In terms of safety,CAM+CT was comparable in terms of the occurrence of all grades of adverse events,but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/meta-static NSCLC patients.CAM+CT was significantly in-creased the occurrence of all grades of adverse events compared with CT,but was comparable in terms of the occurrence of grade 3 or higher treat-ment-related adverse events.In terms of economy,CAM+CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC.CAM+CT has a cost-effectiveness advantage over CT and PEM+CT;and CAM+CT does not have a cost-effectiveness ad-vantage over SIN+CT for patients with mutation-negative locally advanced/metastatic non-squa-mous NSCLC.CONCLUSION:CAM+CT has good ef-ficacy and cost-effectiveness for the first-line treat-ment of locally advanced/metastatic NSCLC,and the safety aspect is compared with CT,PEM or slightly worse.

Objective To predict the potential suitable distribution areas of Sophora japonica cv.jinhuai in China;To provide a references for resource development and expanded cultivation of Sophora japonica cv.jinhuai.Methods Totally 85 pieces of information on the distribution of sample sites were collected and combined data on 72 environmental factors,and the dominant environmental factors affecting the suitability distribution of Sophora japonica cv.jinhuai were analyzed using the maximum entropy(MaxEnt)model and geographic information system software ArcGIS.Results The five dominant environmental factors influencing the suitability distribution of Sophora japonica cv.jinhuai were dry month precipitation,May light radiation,November precipitation,September mean temperature,and October light radiation.The potentially suitable distribution area of Sophora japonica cv.jinhuai in China was mainly concentrated in the transition zone between south-central Hunan Province and northeast Guangxi Zhuang Autonomous Region.Conclusion The results of this study can provide references for the selection of the cultivation areas of Sophora japonica cv.jinhuai and protection of wild reso of Sophora japonica cv.jinhuai.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

ObjectiveTo investigate the relationship between serum 25(OH)D and gestational diabetes mellitus in the second trimester (GDM), to analyze the interaction effect of key risk factors, so as to provide a basis for clinical personalized vitamin D supplementation. MethodsA total of 266 pregnant women who registered and took regular obstetric check-ups in Shanghai Pudong New Area Health Care Hospital for Women and Children from June to December 2022, were selected as the research subjects. According to the results of oral glucose tolerance test (OGTT), the subjects were divided into the GDM group (131) and control group (135). The level of serum 25(OH)D at the time of OGTT were detected and other clinical indicators were followed up. ResultsThe age, systolic blood pressure in early pregnancy, pre-pregnancy BMI, FPG, OGTT 1-hour and 2-hour glucose, GHb, HOMA-IR, TG, AST, Cr, D-D, FDP and SF at 35 weeks’ gestation of the pregnant women were higher in the GDM group than that of the pregnant women in the normal group, while gestational weight gain and serum 25(OH)D level were significantly lower than that of the pregnant women in the normal group. Serum 25(OH)D was negatively correlated with HOMA-IR and WBS’s, but positively correlated with TG and ALT. Serum 25(OH)D was non-linearly correlated with the risk of GDM in an inverted J-shape, and there was an interaction effect of advanced age, pre-pregnancy obesity and vitamin D deficiency on the risk of GDM. ConclusionVitamin D is non-linearly associated with the risk of GDM. The risk of GDM is significantly reduced when serum 25(OH)D level ≥30 ng∙mL^-1.

Objective To compare the positive rate ofthyroid autoantibodies in infertile women with different ovarian reserve function,and investigate the immune factors of diminished ovarian reserve.Methods A cross-sectional study was conducted on infertile women admitted to Department of Reproductive Medicine of Beijing Gynaecology and Obstetrics Hospital from June to December,2020.The levels of anti-Müllerian hormone (AMH ),thyroid stimulating hormone (TSH ),thyroglobulin antibody (TGAb ) and thyroid peroxidase antibody (TPOAb)were detected in the 526 enrolled infertile patients.According to their AMH level,they were divided into normal ovarian reserve group and diminished ovarian reserve group.After they were stratified according to their age,the differences of TSH,TGAb and TPOAb levels were compared in the different age groups to analyze the related factors for diminished ovarian reserve.Results Univariate analysis showed that the diminished ovarian reserve group had significantly higher positive rates of TPOAb (18.8％ vs 11.1％,P=0.024)and TGAb (18.8％ vs 8.0％,P=0.001 )than the normal ovarian reserve group.Multivariate logistic regression analysis indicated that age and TGAb positivity were related to diminished ovarian reserve[OR=1.083(95％ CI:1.021～1.150),P=0.008;OR=1.159(95％ CI:1.034～1.301 ),P=0.011].Subgroup analysis suggested that the positive TGAb and TPOAb were significantly correlated with AMH level in the 36-～40-year-old group (P<0.05).Conclusion The infertile women with diminished ovarian reserve have higher TGAb and TPOAb levels,and the diminishment in those aged 36～40 years might be related to the positive TGAb and TPOAb.

Objective:To investigate the region-specific characteristics of the gut microbiota and evaluate the association of speci?c gut microbes with type 2 diabetes mellitus (T2DM) from the Dongxiang Group in Gansu province, Northwest China.Methods:Fifty-three participants who was born in Dongxiang Autonomous County (Gansu Province) from April 2020 to January 2021 were enrolled, including 25 patients with T2DM recruited from the outpatient departments of internal medicine at The People′s Hospital of Dongxiang County(T2DM group) and 28 healthy controls recruited from the health screening center (HC group). Gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.Results:A total of 936 operational taxonomic units (OTU) were obtained in the two groups. Of note, the HC and T2DM groups had 633 OTU in common. The alpha and beta diversity were different between the two groups ( P<0.05). Shannon index was significantly higher than that in the HC group, and Simpson index was significantly lower than that in the HC group, displacement multivariate analysis of variance was used to compare β diversity between the two groups, and the difference was statistically significant ( P<0.05). At the Phylum level, firmicutes and actinomycetes in T2DM group were significantly higher than those in the HC group (37.97% vs. 22.89%, 5.09% vs. 2.08%), and the differences were statistically significant ( P<0.05). The abundance of Bacteroidetes was significantly decreased (68.00% in T2DM group and 49.75% in HC group), and the difference was statistically significant ( P<0.05). At the genus level, there were 20 genera statistically significant differences between the two groups. The abundance of Bifidobacterium, Escherichia, Shigella, and Tyzzerella_4 levels were significantly increased in the T2DM group, but Prevotella_9, Erysipelotrichaceae_UCG-003, and Roseburia levels were significantly decreased in the T2DM group compared to those in the HC group. Conclusions:There is a significant difference in the gut microbiota between patients with T2DM and healthy individuals of the Dongxiang group in Northwest China. So as to preliminary exploration the intestinal flora characteristics of T2DM in the Dongxiang group.The findings of this study provide a theoretical basis for the prevention and control of T2DM in Dongxiang group in the future.

Objective:To investigate the factors affecting postoperative short-term improvement of consciousness level in patients with prolonged disorders of consciousness after severe traumatic brain injury (sTBI).Methods:A case-control study was conducted to analyze the clinical data of 55 patients with prolonged disorders of consciousness after sTBI admitted to Beijing Tiantan Hospital Affiliated to Capital Medical University and Seventh Medical Center of PLA General Hospital from September 2021 to September 2022. There were 33 males and 22 females, with the age range of 13-68 years [(43.0±15.5)years]. All patients were assessed for the consciousness level using the coma recovery scale-revision (CRS-R) preoperatively and within 48 hours postoperatively. A total of 33 patients were observed in vegetative state and 22 in minimally conscious state preoperatively. The consciousness level was found to be improved in 26 patients (consciousness- improved group), but not improved in the remaining 29 patients (consciousness-unimproved group). Indicators were documented including gender, age, cause of injury, Glasgow coma score (GCS) on admission, course of injury, preoperative consciousness level, operation mode, operation time, intraoperative fluid replenishment, intraoperative urine volume, intraoperative bleeding volume, American Society of Anesthesiologists grade, analgesic regimen and sedation maintenance drugs. A univariate analysis was conducted first to assess those indicators′ correlation with postoperative short-term improvement of consciousness level in patients with prolonged disorders of consciousness after sTBI. Multivariate Logistic regression analysis was then used to determine the independent risk factors for their postoperative short-term improvement of consciousness level.Results:Univariate analysis showed that GCS on admission, course of injury, preoperative consciousness level and analgesic regimen were correlated with short-term improvement of postoperative consciousness level in patients with prolonged disorders of consciousness after sTBI (all P<0.05), whereas gender, age, cause of injury, operation mode, operation time, intraoperative fluid replenishment, intraoperative urine volume, intraoperative bleeding volume, American Society of Anesthesiologists grade and sedation maintenance drugs showed no relation to the improvement of postoperative consciousness level (all P>0.05). Multivariate Logistic regression analysis showed that the GCS ≥7 points on admission ( OR=0.06, 95% CI 0.01, 0.36, P<0.01), preoperative minimally conscious state ( OR=0.09, 95% CI 0.02, 0.40, P<0.01) and intraoperative use of Sufentanil combined with Remifentanil ( OR=0.07, 95% CI 0.01, 0.43, P<0.01) were significantly correlated with postoperative improvement of consciousness level. Conclusion:The GCS on admission (≥7 points), preoperative minimally conscious state and intraoperative use of Sufentanil combined with Remifentanil are independent risk factors affecting short-term postoperative improvement of consciousness level in patients with prolonged disorders of consciousness after sTBI.

Objective     To analyze the clinical efficacy and survival outcome of totally thoracoscopic redo mitral valve replacement and evaluate its efficiency and safety. Methods     The clinical data of patients with totally thoracoscopic redo mitral valve replacement in Guangdong Provincial People’s Hospital between 2013 and 2019 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to determine the risk factors for postoperative death. Results     There were 48 patients including 29 females and 19 males with a median age of 53 (44, 66) years. All the procedures were performed successfully with no conversion to median sternotomy. A total of 15, 10 and 23 patients received surgeries under non-beating heart, beating heart and ventricular fibrillation, respectively. The in-hospital mortality rate was 6.25% (3/48), and the incidence of early postoperative complications was 18.75% (9/48). Thirty-five (72.92%) patients had their tracheal intubation removed within 24 hours after the operation. The 1- and 6-year survival rates were 89.50% (95%CI 81.30%-98.70%) and 82.90%(95%CI 71.50%-96.20%), respectively. Age>65 years was an independent risk factor for postoperative death (P=0.04). Conclusion     Totally thoracoscopic redo mitral valve replacement is safe and reliable, with advantages of rapid recovery, reducing blood transfusion rate, reducing postoperative complications and acceptable long-term survival rate. It is worthy of being widely popularized in the clinic.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.
Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism* ; Protein Serine-Threonine Kinases ; Cell Cycle Proteins/metabolism* ; Cell Cycle/physiology* ; Cyclin-Dependent Kinase 2