BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Objective To assess the nutritional status of vitamin D and associated factors among adults of six ethnic minority groups native to Yunnan Province,and provide evidence for policy making.Methods Between May 2019 and August 2020,a total of 690 adults were selected from Jinuo,Bulang,Jingpo,Deang,Achang and Pumi ethnic groups according to the sex and age composition in the 6th national census.A questionnaire survey and an anthropometric examination were conducted by trained health workers,and serum 25(OH)D levels were determined with high-performance liquid chromatography-tandem mass spectrometry.Results The median of serum 25(OH)D was 28.7(P25～P75∶24.3～33.8)ng/mL,and the prevalence of vitamin D sufficiency,insufficiency and deficiency were 44.2%、47.5%and 8.3%,respectively.There were significant differences in serum 25(OH)D levels among the six ethnic groups(χ2=139.29,P<0.01).Multivariate logistic regression showed that ethnic groups living in higher latitude areas(Pumi,Jingpo,Deang,and Achang),women,and those whose BMI≥24.0 were more likely to be vitamin D insufficient or deficient.Conclusion More than half of the ethnic adults suffer from vitamin D malnutrition which also varies across ethnicities.Further surveillance and interventions among key areas and populations are needed.

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To investigate the clinical efficacy and safety of single-port thoracoscopic surgery for elderly patients with non-small cell lung cancer(NSCLC).Methods The clinical data of 93 patients with NSCLC who underwent thoracoscopic lobectomy or segmentectomy was collected,the patients were divided into uniportal operation group(40 cases,received single-port thoracoscopic surgery)and single-operation port operation group(53 cases,received single-operation port thoracoscopic surgery)according to the operation methods.The operation time,the amount of blood loss,the number of lymph node dissection,chest drainage volume 3 days after surgery,duration of indwelling drainage tube,postoperative hospital stay,visual analogue scale(VAS)score of postoperative pain,and incidence of postoperative complications of patients between the two groups were compared.The cumulative survival rate between the two groups was compared.Results The operation were successfully completed in both groups.There was no statistically significant difference in terms of operation time,the amount of blood loss,the number of lymph node dissection,chest drainage volume 3 days after surgery,duration of indwelling drainage tube,or postoperative hospital stay of patients between the two groups(P>0.05).There was significant difference in VAS score of postoperative pain of patients between the two groups(P<0.05).There was no early death within 1 months after surgery in both groups.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 4 to 30 months of follow-up,there was no significant difference in the cumulative survival rate between the two groups(P>0.05).Conclusion Single-port thoracoscopic lobectomy or segmentectomy for elderly patients with NSCLC has high safety and feasibility,with less trauma,faster recovery and less postoperative pain.

Objective To investigate the association between triglyceride glucose index(TyG)combined with waist circumference(WC)and the risk of new-onset coronary heart disease(CHD)in the middle-aged and elderly people in 10 years of non-interventional follow-up in Luzhou area.Methods A total of 8 647 eligible individu-als participated in epidemiological survey in Luzhou area were selected.The subjects were divided into different groups according to the quartiles of the TyG-WC and followed for ten years.The correlation between different TyG-WC quartile group and 10-year new CHD in middle-aged and elderly population was analyzed by using univariate analy-sis and Cox regression analysis.Results Of the 8 647 participants in the study,484 had new CHD,accounting for 5.5%.The comparison of the number of newly diagnosed CHD subjects grouped by TyG-WC quartiles indicated the 4th quartile group>the 3rd quartile group>the 2nd quartile group>the 1st quartile group,showing statistical significance(P<0.001).Cox regression analysis showed that without adjusting for any variables,the risk of new CHD in 10 years increased with the increase of TyG-WC quartile group,and the differences between the second,third and fourth quartile array and the first quartile array were statistically significant(P<0.05).After adjusting for age and sex and further adjusting for the influence of various influencing factors,the risk of new CHD in 10 years increased with the increase of TyG-WC quartile group.The difference between the third and fourth quartile array and the first quartile array was statistically significant(P<0.05).Conclusion TyG-WC is a risk factor for new-onset CHD in the middle-aged and elderly population in Luzhou area in 10 years of non-interventional follow-up,and TyG-WC may be a predictor of the risk of CHD in the middle-aged and elderly population.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the risk factors for pediatric acute perforation appendicitis,and to construct a nomogram predictive model and conduct the verification.Methods A total of 426 children patients with appendectomy in this hospital from June 30,2020 to June 30,2022 were selected as the study subjects 340 children with acute appendicitis admitted to the hospital from 30 June 2020 to 28 February 2022 were the training set and 86 children patients with appendicitis hospitalized in this hospital from March 1,2022 to June 30,2022 conducted the external validation(verification set).The univariate and multivariate logistic regression models were employed to analyze the independent risk factors of pediatric acute perforation appendicitis.The nomograms predictive model was constructed.The receiver operating characteristic(ROC)curve and calibra-tion curve were used to evaluate the predictive efficiency of the model.The decision curve analysis(DCA)was used to evaluate the application value of the model.Results Of the 426 children,198 were perforated and 228 were not perforated.The univariate and multivariate logistic regression analyses revealed that elevated C-reac-tive protein(CRP),presence of stercorolith in appendiceal cavity,time of onset to visiting hospital ≥2 d and body temperature ≥37.3 ℃ were the independent risk factors for pediatric acute perforation appendicitis(P＜0.05).The Hosmer-Lemeshow test demonstrated that the nomogram predictive model had good fitting(P=0.869),and the area under the curve(AUC)for the training and validation sets were 0.808 and 0.860 respectively,showing the good predictive ability of the model.The calibration curve closely approach the ideal diagonal.The model showed good discrimination,consistency and accuracy.The DC A revealed that the curve was far away from oblique and horizontal lines,and the model had good clinical practicability.Conclusion The constructed nomogram model of pediatric acute perforation appendicitis has good predictive ability and may help clinic to identify as early as possible.

Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.