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 analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P＜0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P＜0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P＜0.01,P＜0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P＜0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.

Objective:To explore the association between internet use and healthy lifestyles in urban adults.Methods:From May to August, 2022, a face-to-face questionnaire survey was conducted in residents aged 18-64 years selected in the urban area of Hangzhou by integrated cluster stratified random sampling and Kish grid method. The information about internet use included the internet use time in the past 7 days and 12 kinds of internet use contents. Using factor analysis and K-means clustering, three types of internet use were summarized, i.e. general type, video game type and working/learning type. Healthy lifestyles were defined as active physical activity, healthy diet habit, non-smoking, non-drinking, healthy weight, and healthy waist circumference. The correlations between internet use and healthy lifestyles were evaluated by using binary logistic regression and multinomial logistic regression analyses.Results:A total of 1 624 participants were included. After adjusting for potential confounding factors, the longer internet use time group (≥8.5 h/d) was less likely to have healthy weight ( OR=0.59, 95% CI:0.41-0.85) and 5-6 healthy lifestyles ( OR=0.55, 95% CI: 0.32-0.96) compared with those with shorter internet use time group (<2.5 h/d). For different types of internet use, it was found that compared with working/learning type group, the general type group was less likely to have healthy diet habits ( OR=0.63, 95% CI: 0.46-0.86), non-drinking ( OR=0.68, 95% CI: 0.47-0.99), healthy waist circumference ( OR=0.59, 95% CI: 0.42-0.84) and 5-6 healthy lifestyles ( OR=0.40, 95% CI: 0.23-0.69), the video game type group was less likely to have active physical activity ( OR=0.73, 95% CI: 0.55-0.97) and healthy diet habits ( OR=0.79, 95% CI: 0.62-0.99). Conclusion:Too long internet use (≥8.5 h/d), general type and video game type of internet use were associated with unhealthy lifestyles.

Objective To observe the effect of neuromuscular electrical stimulation on bone angiogene-sis and osteoporosis induced by denervation in sarcopenia osteoporosis rats,and explore the correlation of the miRNA expression level in circulating extracellular vesicles to bone angiogenesis and osteoporo-sis.Methods Ten-week-old male Sprague-Dawley rats were randomly divided into a sham operation control group(con,n=8),a double leg tibial nerve loss group(DD,n=8)and a double leg tibial nerve loss + right leg electrical stimulation group(D+ES,n=8).The tibial nerve of both legs was re-moved in DD and D+ES groups,and one week later the D+ES group received 8-week neuromuscular electrical stimulation.Samples were taken 24 hours after the last stimulation.Trabecular bone parame-ters were detected using micro-CT and its morphology was observed using hematoxylin and eosin(HE)staining.Immunohistochemical staining was used to identify the vascular markers platelet endothe-lial cell adhesion molecule-1(PECAM-1/CD31)and vascular endothelial growth factor A(VEGFA).Moreover,plasma exosomes were extracted and purified,and the vesicles were identified by electron microscopy,nanoparticle tracking analysis(NTA)and Western blotting.Meanwhile,the real time PCR was used to determine the expression of myogenic miR-1,miR-133a,miR-133b and miR-206 in exo-somes.Results(1)Compared with the CON group,the volume and weight of gastrocnemius and sole-us muscles in the DD group reduced significantly(P＜0.001),and the tibial trabecular bone parameters changed pathologically.After 8-week stimulation,compared with the DD group,the volume and weight of gastrocnemius and soleus muscles in D+ES group increased significantly(P＜0.05),and tibial trabecular bone parameters improved significantly.(2)The immunohistochemical staining results indicat-ed that,compared with CON group,the expression of CD31 and VEGFA in the tibia of DD group re-duced significantly,while that of the D+ES group increased significantly compared with DD group.(3)The results of NTA showed that,compared with CON group,the concentration of circulating extra-cellular vesicles in the DD group decreased significantly(P＜0.001),and the expression of miR-1,miR-133a,miR-133b and miR-206 in exosomes increased significantly(P＜0.05,P＜0.01,P＜0.05,P＜0.05 respectively).Compared with the DD group,the concentration of circulating exosomes in D+ES group increased significantly(P＜0.05),and the expression of the above four miRNAs decreased signifi-cantly(P＜0.05 for all).Conclusion Tibial nerve denervation can successfully establish the model of sar-copenia osteoporosis and neuromuscular electrical stimulation significantly relieves such denervation in-duced changes.Moreover,electrical stimulation also significantly increases the concentration of circulat-ing exosomes,and the expression of myogenic miRNAs carried by them,which suggests that the latter may be related to bone angiogenesis and the progression of osteoporosis.

Bioactive peptides play important roles in promoting human health, such as lowering blood pressure, blood sugar and blood lipid, anti-obesity, and anti-cancer. Thus, exploring functional bioactive peptides and developing efficient production technologies are of crucial importance. Herein, we review the development of function discovery and production technology for natural bioactive peptides. Presently, the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides. The top-down approach includes the direct extraction and identification for functional discovery, and the direct extraction, enzymatic hydrolysis and microbial fermentation for production. The bottom-up approach includes the polypeptide modification and database mining for functional discovery, and the chemical synthesis, enzyme synthesis, recombinant expression and cell-free synthesis for production. The top-down approach is usually associated with complicated process, lower efficiency, higher cost, harder quality control, and uncertain functionality, while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods. With the technology development of sequencing and mass spectrometry, it is easier to obtain the proteomic information of various organisms at the molecular level. Based on the proteomic information, the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone, thus providing a new strategy for the rapid development and production of natural active peptides.
Fermentation ; Humans ; Mass Spectrometry ; Peptides/metabolism* ; Proteomics ; Technology

Objective:To analyze the relationship between the developmental eye movement (DEM) test results and the vocabulary size in Chinese children with developmental dyslexia.Methods:A cross-sectional study was conducted.A total of 1 243 fifth grade students from 10 primary schools were enrolled from September to December 2019 in Tianjin, among which there were 664 males and 579 females, with the average age of (10.68+ 0.53) years old.The Chinese vocabulary test and intelligence test were carried out.Eighty-five dyslexic children with subaverage vocabulary size were selected as the experimental group and 54 normal children were selected as the control group.The DEM test was conducted in the two groups, and the vertical time, the horizontal adjustment time, the ratio of horizontal to vertical time and the total number of errors were recorded and analyzed.The differences in positive rate of dyslexia, various DEM test indicators between different genders and different groups were analyzed.The correlations between vocabulary size and vertical time, horizontal adjustment time, the ratio of horizontal to vertical time and the total number of errors were analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of School of Optometry, Tianjin Vocational Institute (No.ysgxyll001). Written informed consent was obtained from the guardian of each subject.Results:The total positive rate of dyslexia was 6.83%(85/1 243), and the positive rate of 9.33%(62/664) in boys was higher than 3.97%(23/579) in girls, with a significant difference between them( χ2=13.974, P<0.001). There were no statistically significant differences in age, vocabulary size, vertical time, horizontal adjustment time, and the ratio of horizontal to vertical time between different genders in the control group (all at P>0.05). The vocabulary size of girls in the experimental group was larger than that of boys, showing a statistically significant difference ( t=-2.259, P=0.027). There was no significant difference in age, vertical time, horizontal adjustment time, and the ratio of horizontal to vertical time (all at P>0.05). The vertical time and horizontal adjustment time of the experimental group were longer than those of the control group, and the differences were statistically significant ( t=-4.848, -4.297; both at P<0.001). There was no statistically significant difference in the ratio of horizontal to vertical time between the two groups ( t=0.126, P=0.900). The total number of errors was 0(0, 1) in the experimental group, which was higher than the control group 0(0, 0), with a significant difference between them ( H=1.979, P=0.001). The vocabulary size of students in the two groups was negatively correlated with the vertical time, horizontal adjustment time and the total number of errors ( r=-0.397, P<0.001; r=-0.355, P<0.001; r s=-0.180, P=0.034), and was not obviously correlated with the ratio of horizontal to vertical time ( r=0.038, P=0.656). Conclusions:The DEM test scores of Chinese children with developmental dyslexia are higher than those of normal children, and there is no difference between different genders.The lower the scores of vocabulary size test, the higher the scores of DEM test.

Objective:To identify the threshold of a health warning system based on the association of apparent temperature and years of life lost (YLL).Methods:Daily mortality records and meteorological data were collected from 364 Chinese counties for 2006-2017. Distributed lag nonlinear model and multivariate Meta-analyses were applied to estimate the association between the apparent temperature and YLL rate. A regression tree model was employed to estimate the warning thresholds of the apparent temperature. Stratified analyses were further conducted by age and cause of death.Results:The daily YLL rate was 23.6/10 5. The mean daily apparent temperature was 15.7 ℃. U-shaped nonlinear associations were observed between apparent temperature and YLL rate. The actual temperature-caused YLL rate for the elderly was higher than the young population. The daily excess deaths rate increased with the higher effect levels. Conclusions:Regression tree model was employed to define the warning threshold for meteorological health risk. The present study provides theoretical support for the weather-related health warning system.

Increasing evidence suggests that vitamin D deficiency may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM).T2DM manifests as a result of insulin resistance,increased hepatic glucose production and β-cell failure.Vitamin D metabolites are thought to play an important role in increasing insulin sensitivity and facilitating insulin exocytosis which is mediated both by direct mechanism through the availability of vitamin D receptors in several tissues and indirect mechanism through the changes in calcium levels.Vitamin D has also been shown to decrease inflammatory cytokines which plays an important role in insulin resistance and β-cell apoptosis.Several studies have confirmed that vitamin D is closely related to the long-term complications of diabetes.Low levels of vitamin D can exacerbate diabetic peripheral neuropathy,nephropathy,and retinopathy.Although diabetic patients with vitamin D deficiency is widespread,the existence of vitamin D deficiency and diabetes complications is still controversial,this article will review the relationship between vitamin D and the microvascular complications of T2DM.

Objective To assess the clinical curative effect of accordion technique in the treatment of tibial delayed union or nonunion.Methods From February 2016 to December 2017,data of 11 patients with tibial delayed union (n=8) or non-union (n=3) who had been treated by accordion technique with an Ilizarov ring external fixator were retrospectively analyzed.10 males and 1 female were included in our study,with an average age of 41.9 years (range,21-63 years).There were 5 cases of docking site delayed union after Ilizarov transport for chronic tibial osteomyelitis.There were 3 cases of fracture site delayed union after external fixation for open tibia comminuted fracture.There were 3 cases of nonunion after tibia closed fracture,including 2 cases who had hybrid external fixation treatment,and 1 case who had conservative treatment.All the cases received accordion technique using Ilizarov ring external fixators.First,gradual compression at the fracture site was conducted until the bony contact was seen on a radiograph.After bony contact,compression was continued at a rate of 0.85 mm/d for a week,followed by distraction of 0.85 mm/d for 2-3 weeks.Afterward,a second compression was conducted using same rate and time with the distraction procedure.And there was a 7-day latent period between compression and distraction.One or two cycles of compression-distraction were needed before union was present radiographically.Results Bony union was obtained in all 11 patients after a mean time of 5.4 months (from 3 to 9 months).The mean follow-up for the 11 patients was 15.2 months (from 11 to 29 months).The mean duration of the accordion technique treatment was 50.2 d (range,35-67 d).The accordion technique was used 1 time for 8 patients,and 2 times for 3 patients.The mean duration of bone consolidation was 114.9 d (range,64-239 d).According to Paley evaluation criteria,osseous results were excellent in 8 cases,good in 3 cases,with a good to excellent rate of 100％(11/11);functional results were excellent in 7 cases,and good in 4 cases,with a good to excellent rate of 100％(11/11).Conclusion The accordion technique is a minimal invasive,safe and reliable treatment program for tibial delayed union or nonunion.

Based on the statistics of 350 technical evaluations of changes in licensing items of class Ⅱ passive and active medical devices completed in Henan province from July 2017 to November 2018, this paper summarized and analysed the common problems and requirements listed in the correction notifications of the technical evaluation, and put forward relevant countermeasures or suggestions, with a view to further speeding up the evaluation and approval of medical devices.
Equipment and Supplies ; standards ; Government Regulation ; Licensure