BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

In order to solve the problems of difficult test, high cost and long cycle in the development of large-scale airborne negative pressure isolation system, the simulation analysis of negative pressure response characteristics is carried out around various aviation conditions such as aircraft ascending, leveling and descending, especially rapid decompression, based on the computational fluid dynamics (CFD) method. The results showed that the isolation cabin could achieve -50 Pa pressure difference environment and form a certain pressure gradient. The exhaust air volume reached the maximum value in the early stage of the aircraft's ascent, and gradually decreased with the increase of altitude until it was level flying. In the process of aircraft descent, the exhaust fan could theoretically maintain a pressure difference far below -50 Pa without working; Under the special condition of rapid pressure loss, it was difficult to deal with the rapid change of low pressure only by the exhaust fan, so it was necessary to design safety valve and other anti-leakage measures in the isolation cabin structure. Therefore, the initial stage of aircraft ascent is the key stage for the adjustment and control of the negative pressure isolation system. By controlling the exhaust air volume and adjusting parameters, it can adapt to the change of low pressure under normal flight conditions, form a relatively stable negative pressure environment, and meet the needs of biological control, isolation and transport.
Aircraft ; Computer Simulation ; Aviation/instrumentation* ; Humans ; Hydrodynamics ; Air Pressure ; Equipment Design ; Pressure

OBJECTIVE To study the intervention effects of Wenshen Tongluo Zhitong Recipe(WTZR)on macrophage senes-cence and senile osteoporosis.METHODS The senescent macrophage model was established using hydrogen peroxide(H2 O2)and subsequently divided into four groups:control,model,low-dose drug-treated serum,and high-dose drug-treated serum.β-galactosidase staining,Western blot and qPCR were employed to evaluate the mRNA expression of senescence markers p21 and p53.ROS staining and JC-1 staining were applied to assess mitochondrial function in macrophages.The mRNA levels of Interleukin(IL)-6,IL-10,CD206,and inducible nitric oxide synthase(iNOS)were determined by qPCR analysis.Immunofluorescence was used to evaluate argi-nase(ARG1)and iNOS protein expressions for assessing the impact of drug-containing serum on macrophage polarization.qPCR analy-sis was conducted to measure osteocalcin(OCN),collagen type Ⅰ alpha 1(Col1a1),runt-related transcription factor 2(Runx2)mRNA levels as osteoblast-related markers;ALP staining along with alizarin red staining were performed to evaluate the effect of macrophage conditioned medium treated with drug-containing serum on bone marrow mesenchymal stromal cell(BMSC)osteogenic differentiation.C57BL/6J mice were randomly allocated into four groups:control group,model group,WTZR low-dose group,and WTZR high-dose group.The senile osteoporosis(SOP)mouse model was established by D-galactose.Micro-CT scanning analyzed fe-mur microstructure while HE staining detected pathological changes in femur bone tissue samples collected from each experimental con-dition.Furthermore,Western blot was used to detect the senescence-related molecules p21 and p53 and the osteogenesis-related mark-ers OCN and Runx2,qPCR analysis measured tibial expression levels of senescence-related molecules(p21,p53)as well as macro-phage polarisation-related molecules(IL-6,iNOS,CD206,and IL-10)to assess the effect of this compound on a mouse model simula-ting SOP.RESULTS Following intervention with serum containing WTZR,there was a significant decrease in the number of senes-cent positive cells compared to the model group.Additionally,there was a notable decrease in p21 and p53 mRNA and proteins expres-sion(P＜0.05,P＜0.01,P＜0.001).Furthermore,drug-containing WTZR effectively inhibited ROS production induced by H2 O2 and mitigated mitochondrial membrane potential reduction in macrophages(P＜0.05,P＜0.001).Treatment with drug-containing WTZR re-sulted in down-regulated mRNA expression of M1-related gene iNOS(P＜0.05)while up-regulating mRNA expression of M2-related genes CD163 and CD206(P＜0.05).The drug-containing WTZR significantly reduced fluorescence intensity for iNOS(P＜0.01)while increasing ARG1(P＜0.05)fluorescence intensity.Moreover,conditioned medium from macrophages treated with drug-containing ser-um increased ALP positive cell count(P＜0.01,P＜0.001),alizarin red positive area(P＜0.05),as well as Col1a1,Runx2 and OCN mRNA expression levels(P＜0.05,P＜0.01).The Tb.N,BMD,and BV/TV were significantly higher in the WTZR group compared to the model group(P＜0.05,P＜0.01,P＜0.001);meanwhile,Tb.Sp was notably lower than that observed in the model group(P＜0.05,P＜0.01);bone trabeculae were significantly improved,increased in number and widened.Additionally,the compound could significantly inhibit the D-galactose induced up-regulation of tibial senescence-related genes and proteins p21 and p53(P＜0.05,P＜0.001,P＜0.0001),promote the expression of osteogenesis-related markers OCN and Runx2 protein(P＜0.01,P＜0.0001),promote the down-regulation of M1 related genes IL-6 and iNOS(P＜0.05),and promote the expression of M2 related genes IL-10 and CD206(P＜0.05,P＜0.01).CONCLUSION Wenshen Tongluo Zhitong Recipe may play an anti-osteoporosis effect by inhibiting macrophage senescence and promoting the osteogenic differentiation of BMSC.

Objective:To analyze the mutation of T-cell and B-cell epitopes derived from HBV PreS-S protein in occult hepatitis B virus (OHBV) and investigate the biological mechanisms of occult hepatitis B virus infection (OBI) and HBsAb positive OBI.Methods:The PreS-S region of OBI samples were amplified by nested PCR, the products were sequenced and HBV genotypes were determined. The mutations of T-cell and B-cell epitopes derived from HBV PreS-S protein were analyzed and compared among groups of HBV genotypes and the presence of HBsAb. The affinity of the high frequency of T-cell epitope substitutions were analyzed by SYF PEITHI, the changes of antigenic characteristics of high frequency of B-cell epitope substitutions were analyzed by Ab Designer, Expasy ProtParam tool, Epitope Prediction and Analysis Tools.Results:The PreS-S region of HBV was amplified in 21 samples, including 4 HBsAb+ OBI B, 6 HBsAb-OBI B, 6 HBsAb+ OBI C, 5 HBsAb-OBI C. The mutation rates in PreS-S region of OBI were significantly higher than wild type HBV strains(OBI Bvs. WT B: 2.64%: 0.66%, P<0.001; OBI Cvs. WT C: 3.67%: 1.19%, P<0.001). The mutation rates of the immunoreactive area were significantly higher than non-immunoreactive area in OBI (OBI B: 3.57%: 1.86%, P=0.005; OBI C: 4.78%: 2.65%, P<0.001). The mutation rates of the immunoreactive and non-immunoreactive area in OBI C were higher than OBI B, but there was no statistically significant difference (immunoreactive area: 4.78%: 3.57%, P=0.107; non-immunoreactive area: 2.65%: 1.86%, P=0.142). The mutation rates of T-cell and B-cell epitopes of HBsAb-OBI were higher than HBsAb+ OBI, although there was no significant difference (HBsAb-OBI Bvs. HBsAb+ OBI B: 4.17∶3.01, P=0.303; HBsAb-OBI Cvs. HBsAb+ OBI C: 5.65∶4.26, P=0.207). The affinity analysis of 4 high frequency T-cell epitope substitutions, including T47A/K, S174N, L175S, V177A, showed that the changes of affinity of most mutation sites were not obvious; the antigenicity analysis of 3 high frequency B-cell epitope substitutions, including G73S, K122R, I126M/T, did not show noticeable changes and the hydrophilicity, surface accessibility of some mutation sites were even better than wild strain. Conclusions:The mutation rates in PreS-S region of OBI were significantly higher than wild type HBV strains. The mutation rates of the immunoreactive area were higher than non-immunoreactive area in OBI. The variant activity of OBI C was higher than OBI B. The mutations of OBI might occur randomly and were not selected by antibody pressure. Single epitope and multi-epitopes combinational mutations might be a reason for OBI.

Objective: To explore of executive function in obese adolescents, so as to provide a reference for executive function enhancement intervention in obese adolescents. Methods: A convenience sample of 1 227 adolescents aged 13-18 years was selected from 2 secondary schools in Taiyuan City during March-April 2023. The Flanker task, N-back task and More odd shifting task was used to compare the different subfunctions of executive function (refreshing function, shifting function, inhibiting function) of 61 obese adolescents and 70 normal weight adolescents. Independent samples t-tests was used for between group comparisons and Cohen s d -tests was used to calculate between group differences in executive function between the two groups of adolescents. Results: Compared with the group of normal weight, time responses of the inhibitory function [(29.73±19.55)ms], the refreshing function [1-back: (1 088.75±275.76)ms, 2-back:( 1 285.44± 355.16)ms] and the shifting function [(380.34±153.18) ms] in the obese group were significantly longer than those in the normal weight group [(14.86±20.27, 888.38±286.57, 1 126.20± 287.43 , 323.12±134.71) ms] ( t =4.26, 4.06, 1.92,2.26, P < 0.05 ); inhibitory function (0.91±0.09) and 1-back (0.73±0.24) were also significantly less correct than in the normal weight group (0.94±0.05, 0.83±0.21) ( t =-2.04, -2.04, P <0.05). Obese adolescents showed moderate adverse effect sizes in the inhibition function ( d =0.746,0.712) and the refresh function 1-back, and smaller adverse effect sizes in the refresh function 2-back and the conversion function( d =0.497,0.398). Conclusion Obese adolescents have significant executive function deficits, but the degree of adverse varies across sub-functions, with inhibitory function being the core deficit component of executive function in obese adolescents.

【Objective】 To explore the distribution of serological markers related to samples whose serological test results were inconsistent with HBV DNA test results among voluntary blood donors in Xi′an. 【Methods】 A total of 71 HBsAg ELISA positive and NAT non-reactive (ELISA+ /NAT-)blood samples were collected from Shaanxi Blood Center from November 1, 2022 to April 30, 2023. The serological markers of hepatitis B were detected by electrochemiluminescence method, and the HBV S region and C region gene fragments were amplified by nested-PCR. 【Results】 The positive rate of nested-PCR in double ELISA+ /NAT- group(n=30) was statistically higher than that of ELISA+ /NAT- group(n=41)(60% vs 24.4%, P<0.05). Donors in double ELISA+ /NAT- group were all first-time blood donors, with the positive rate of anti-HBc in serum of 100%, and the serological pattern was mainly positive for items 1, 4 and 5 items(80%). Among the ELISA+ /NAT- group, 31.7% were repeat blood donors, with the positive rate of anti-HBc in serum of only 19.51%, and the serological patterns were mainly single anti-HBs positive (43.90%) and all negative (36.58%). 【Conclusion】 There are false positives in the test results of ELISA+ /NAT- group, which leads to unnecessary blood discarding. Meanwhile, the samples with negative NAT may have low levels of HBV DNA, which may lead to missed detection. It is suggested that multiple systems and methods should be applied to trace the blood donors who are HBsAg positive and NAT non-reactive, so as to improve the accuracy of HBV screening of blood donors and reduce blood waste.

Objective: To explore the characteristics and related factors of adolescent executive function, so as to provide theoretical basis for promoting the development of adolescent executive function. Methods: A total of 5 018 adolescents aged 13-18 from Shanghai, Suzhou, Taiyuan, Wuyuan, Xingyi and Urumqi were selected by convenient cluster random sampling method from September to December 2022, and their basic information, family status, lifestyle behavior, physical fitness and executive function were investigated by questionnaire survey. Considering the heterogeneity between schools, a multilevel Logistic model was established to analyze the related factors of adolescent executive function. Results: The inhibitory function of high school students was better than that of middle school students (Z=-2.69). In terms of refreshment function, high school students were superior than middle school students (1-back:Z=-11.32; 2-back:Z=-11.36), and male students were superior than female students (2-back:Z=-2.18); in terms of shifting function, high school students were superior than middle school students (Z=-2.63), and boys were superior than girls (Z=-7.10)(P<0.05). The results of multilevel model analysis showed that the executive function of adolescents was clustered at the school level. At the individual level, junior high school refreshment function (1-back:β=56.94; 2-back:β=127.00), and shifting function (β=35.64) were worse than that of high school students; the refreshment function 2-back (β=-21.24) and shifting function (β=-28.42) of male students were better than those of female students; the refreshment function 2-back of nononly child was better than that of only child (β=-19.36); refreshment function of low fitness was worse than that of high fitness (β=37.35); the shifting function of the video screen time not up to standard was better than that of the standard (β=-14.30)(P<0.05). Conclusions The executive function of high school students is better than that of middle school students, the refreshment function and shifting function of boys are better than that of girls. Family environment, lifestyle and physical health are significant factors related to executive function of Chinese adolescents. By raising awareness of the major supporting and impeding factors for executive functioning in adolescents, it can help to develop effective intervention programs for adolescents.

[摘 要] 目的：系统评估经动脉化疗栓塞（TACE）和酪氨酸激酶抑制剂（TKI）联合（TT）联合或不联合PD-1抗体（PD-1Ab）治疗晚期肝细胞癌（aHCC）的疗效与潜在不良反应（AE）。方法：检索PubMed、中国知网（CNKI）、Embase、Web of Science等数据库，时限为各数据库建库始至2024年1月31日。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用Stata16.0软件进行Meta分析。结果：纳入17项研究，共2 334例aHCC患者。Meta分析结果显示，与TT疗法相比，PD-1Ab的加入能显著改善aHCC患者的总生存期（OS）[HR = 0.44，95% CI（0.36，0.51），P < 0.000 01]和无进展生存期（PFS）[HR = 0.47，95% CI（0.42，0.52），P < 0.000 01]，同时提高aHCC患者的客观缓解率（ORR）[HR = 1.65，95% CI（1.46，1.86），P < 0.000 01]和疾病控制率（DCR）[HR = 1.26，95% CI（1.15，1.38），P < 0.000 01]；不同基线资料如ECOG-PS、肝外转移与否、BCLC分期、肿瘤大小、Child-Pugh评分及肝门静脉侵犯与否等aHCC患者均可从TT PD-1Ab疗法中获益；两治疗方案间全级别与 ≥3级AE的总发生率无显著差异，但高血压、甲状腺功能减退及反应性皮肤血管增生等症状在接受TT PD-1Ab治疗的患者中更为常见。结论：相较于TT疗法，PD-1Ab的加入可显著延长aHCC患者OS和PFS，并提高其整体ORR与DCR；TT PD-1Ab治疗组患者发生全级别及≥ 3级AE的整体发生率没有显著增加，整体耐受性良好，但在高血压、皮肤与黏膜及甲状腺AE上有较高的发生率，应予以重视。

Abstract Executive function is an advanced cognitive process aimed at the flexible coordination, optimization, and control of the cognitive processes of task solving in order to accomplish a specific task, ensuring that the individual produces effective behaviors, including inhibitory control, working memory, and cognitive flexibility. Given the sensitivities and specificities that characterize an individual s physical and mental development during adolescence, this period is critical for the development of executive function in adolescents. In the paper, the influencing factors of adolescents executive function development are systematically described from three dimensions, namely, biology, environment and lifestyle; by analyzing the mechanisms and differences in the effects of different influencing factors, this editorial provides a scientific basis for adolescents executive function improvement and intervention.