WIN55212-2 inhibits glycolysis and attenuates acute lung injury in septic mice by regulating mTOR/HIF-1α/PFKFB3 signaling pathway / 中国病理生理杂志

AIM:To investigate the effects of cannabinoid receptor agonist WIN55212-2(WIN)on acute lung injury(ALI)in septic mice,and to explore its potential mechanisms through glycolysis.METHODS:A mouse model of septic ALI was established by intraperitoneal injections of lipopolysaccharide(LPS).Male C57BL/6J mice were randomly divided into 4 groups(n=6):(1)control group;(2)LPS group,receiving intraperitoneal injections of LPS at 10 mg/kg;(3)LPS+WIN group,receiving 1 mg/kg WIN intraperitoneally 30 min prior to LPS injection;(4)LPS+WIN+MHY1485[mammalian target of rapamycin(mTOR)activator]group,receiving 10 mg/kg MHY1485 intraperitoneally 1 d before LPS injection and 1 mg/kg WIN plus 10 mg/kg MHY1485 30 min before LPS injection.Tissues were collected 24 h after modeling for analysis.Lung indexes were calculated,and histopathological changes of lung tissues were observed via he-matoxylin-eosin(HE)staining.Inflammatory cytokines interleukin-1β(IL-1β)and IL-10 in lung tissues,and lactic acid and lactate dehydrogenase A(LDHA)in serum were quantified using ELISA.The levels of mTOR/hypoxia-inducible fac-tor-1α(HIF-1α)/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway-related proteins were assessed by Western blot.RESULTS:Compared with control group,the LPS group exhibited an increased lung in-dex,significant lung tissue damage,an increase in IL-1β levels(P＜0.05),a decrease in IL-10 levels(P＜0.05),and el-evated expressions of lactate and LDHA(P＜0.05),along with increased levels of phosphorylated mTOR(p-mTOR),HIF-1α and PFKFB3 proteins(P＜0.05).The LPS+WIN group showed improvements with a reduced lung index(P＜0.05),lessened lung injury,decreased IL-1β levels(P＜0.05),increased IL-10 levels(P＜0.05),and lower levels of lactic acid,LDHA,p-mTOR,HIF-1α,and PFKFB3(P＜0.05).Conversely,the LPS+WIN+MHY1485 group displayed increased lung indexes and lung tissue damage,elevated IL-1β levels(P＜0.05),reduced IL-10 levels(P＜0.05),and higher expressions of lactic acid,LDHA,p-mTOR,HIF-1α and PFKFB3(P＜0.05)compared to the LPS+WIN group.CONCLUSION:WIN55212-2 mitigates sepsis-induced ALI,potentially by modulating the mTOR/HIF-1α/PFKFB3 sig-naling pathway,thereby inhibiting glycolysis and alleviating inflammatory responses.

Electrocardiogram evaluation and related factor analysis in patients with gestational diabetes mellitus complicated by depressive disorder / 中国基层医药

Objective:To investigate electrocardiogram (ECG) characteristics and related factors of gestational diabetes mellitus (GDM) complicated by depressive disorder.Methods:The clinical data of 243 patients with GDM who received treatment at Peking University Third Hospital from September 2021 to December 2022 were retrospectively analyzed. According to the scoring results of the Self-rating Depression Scale (SDS), these patients were divided into an observation group (GDM + depressive disorder, n = 51) and a control group (GDM alone, n = 192). The χ2 test was used to analyze the relationship between GDM complicated by depressive disorder and ECG diagnosis results. Additionally, the t-test was used to compare ECG indicators between the two groups. Results:Compared with the control group, patients in the observation group had a higher incidence of abnormal ECG indicators, including bradycardia ( χ2 = 4.68, P = 0.030), premature contraction ( χ2 = 10.78, P = 0.001), and atrioventricular block ( χ2 = 15.04, P < 0.001). However, there were no significant differences in the incidences of tachycardia, bundle branch block, or ST-T changes between the two groups (all P > 0.05). Compared with the control group, the observation group exhibited significantly increased heart rate [(73.43 ± 8.24) beats/min vs. (67.22 ± 5.08) beats/min], maximum QT interval [(419.09 ± 36.00) ms vs. (351.95 ± 32.07) ms], minimum QT interval [(363.31 ± 30.78) ms vs. (316.52 ± 29.10) ms], and QT dispersion [(55.78 ± 17.87) ms vs. (35.42 ± 13.18) ms, t = -5.13, -12.95, -10.08, -7.60, all P < 0.001]. Conclusion:Among patients with gestational diabetes mellitus, those with depressive disorder have an increased risk of exhibiting abnormal electrocardiogram patterns compared with those without depressive disorder.

Total saponins of Panax japonicus regulates the inhibitory effect of AMPK/mTOR/ULK1 pathway mediated ferritinophagy on ferroptosis of cardiomyocytes in diabetic cardiomyopathy rats / 中华内分泌代谢杂志

Objective:To investigate the effect of total saponins of Panax japonicus(TSPJ) on ferroptosis of myocardial cells in diabetic cardiomyopathy(DCM) rats and underlying mechanism.Methods:Experiment 1: SD rats were divided into control group, DCM group, low-dose TSPJ group, high-dose TSPJ group, and metformin(Met) group, with 10 rats in each group. Experiment 2: SD rats were divided into control group, DCM group, TSPJ group, adenosine monophosphate-activated protein kinase(AMPK) inhibitor Compound C group, and TSPJ+ AMPK agonist AICAR group, with 10 rats in each group. Except for the control group, all rats were intraperitoneally injected with streptozotocin to construct a DCM model. After 8 weeks of corresponding drug intervention, the body weight as well as glucose and lipid metabolism of rats in each experimental group were assessed, and the cardiac function indicators were detected with echocardiography. The levels of serum lactate dehydrogenase(LDH), cardiac troponin I(cTnI) and creatine kinase isoenzyme MB(CK-MB) were detected by ELISA technique. The pathological changes of myocardial tissue were observed using hematoxylin-eosin(HE) staining. The levels of dismutase(SOD), glutathione(GSH), malondialdehyde(MDA), reactive oxygen species(ROS) and Fe 2+ in myocardial tissue were detected. Western blot was used to detect ferroptosis, ferritinophagy, and the AMPK/mammalian target of rapamycin/UNC-51-like kinase 1(mTOR/ULK1) signaling pathway related proteins expression in myocardial tissue. Results:Compared with control group, left ventricular ejection fraction(EF), left ventricular short axis shortening rate(FS), peak blood velocity ratio(E/A) between early and late diastolic periods were significantly decreased in DCM group, left ventricular inner diameter(LVEDd) was increased, and the serum LDH, cTnI, CK-MB were increased, the levels of SOD, GSH were decreased, MDA, ROS, Fe 2+ were increased in myocardial tissue, the expressions of TFR1, NCOA4 LC3-II/LC3-I, Beclin-1, phosphorylated AMPK and phosphorylated ULK1 were increased, the expressions of GPX4, SLC7A11 and phosphorylated mTOR were decreased. Compared with DCM group, the above indicators of rats were significantly improved in each treatment group. Compared with the TSPJ group, the AMPK agonist AICAR reversed the effects of TSPJ on ferroptosis and ferritinophagy mediated by the AMPK/mTOR/ULK1 pathway in DCM rat cardiomyocytes. Conclusion:TSPJ can inhibit ferroptosis in DCM rat cardiomyocytes and improve myocardial injury by regulating AMPK/mTOR/ULK1 mediated ferritinophagy.

Correlation analysis of frailty and health literacy in elderly patients with chronic cardiac insufficiency / 沈阳医学院学报

Objective:To analyze the correlation between frailty and health literacy in elderly patients with chronic cardiac insufficiency.Methods:The convenience sampling method was used to select 290 elderly patients with chronic cardiac insufficiency who were hospitalized in the Department of Geriatrics and Department of Cardiovascular Medicine of a tertiary first-class hospital in Wuhu City from Mar 2022 to Jun 2022.The patients were investigated with the general information questionnaire,FRAIL scale,Health Literacy Management Scale,etc.Spearman analysis was used to analyze the correlation between frailty and health literacy.Binary logistic regression were used to analyze the risk factors of frailty in elderly patients with chronic cardiac insufficiency.Results:The incidence of frailty in elderly patients with chronic cardiac insufficiency was 22.8% .Spearman analysis showed that the total score of health literacy was negatively correlated with frailty(r=-0.291,P= 0.000).Results of binary logistic regression analysis showed that health literacy score(OR=0.419,95% CI:0.266-0.908),long-term insomnia(OR=6.466,95% CI:2.099-19.914),nutritional risk(OR=11.202,95% CI:3.983-31.508),depression risk(OR=10.014,95% CI:1.963-51.075),chronic disease types≥5(OR=12.784,95% CI:3.811-42.878),exercise self-efficacy(OR=0.512,95% CI:0.304-0.956),and chronic disease information acquisition ability(OR=0.512,95% CI:0.304-0.956)were independent predictors of frailty in elderly patients with chronic cardiac insufficiency(P＜0.05).Conclusions:The incidence of frailty in elderly patients with chronic cardiac insufficiency is high,and clinical staff should pay more attention to the elderly with frailty,especially patients with long-term insomnia,risk of nutrition and depression,coexistence of chronic diseases,low level of health literacy and exercise self-efficacy.Targeted measures should be actively taken to improve the quality of life of patients and reduce the readmission rate.

Analysis of the effect of fudosteine on induced sputum components in patients with stable neutrophil-dominated COPD / 中国临床药理学与治疗学

AIM: To observe the effect of fudosteine on induced sputum cell components and lung function in patients with stable neutrophil-dominated COPD. METHODS: From October 2019 to October 2022, 53 patients with stable COPD were selected and divided into fudosteine group and placebo group. The placebo group was treated with routine treatment, and the fudosteine group was treated with fudosteine on the basis of routine treatment. The two groups were treated for 6 months. The clinical symptoms [Saint George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Modified British Medical Research Council Dyspnea scale (MMRC), Breathlessness, Cough, and Sputum Scale (BCSS)], lung function index, induced sputum cytology analysis and other related examination results were recorded in detail before and after treatment. RESULTS: (1) Compared with the baseline, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) of the two groups were improved after treatment, and the differences were statistically significant (P<0.05). However, after treatment, there was no significant difference in pulmonary function between the two groups except for the percentage of carbon monoxide diffusion in the predicted value (DLCO%pre) (DLCO%pre in the fudosteine group was higher than that in the placebo group). (2) After treatment, the total number of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group. Compared with the number of cells in each component at baseline, the total number of induced sputum cells and neutrophil count in the fudosteine group were significantly lower (P< 0.05). CONCLUSION: Fudosteine treatment in patients with stable neutrophil-dominated COPD can improve lung function, reduce the total number of induced sputum cells and the total number of neutrophils, thereby improving airway inflammation.

Progress in the application of AIT in allergic airway diseases / 中国临床药理学与治疗学

Allergen specific immunotherapy (AIT) is to identify the patient's allergen, give the patient repeated exposure to the allergen extract, and gradually increase the concentration and dose until the target maintenance dose is reached, so that the patient can develop tolerance to the allergen, which is the only treatment that can regulate the pathogenesis of allergic diseases and change its natural course. In recent years, domestic and foreign scholars have made great progress in the clinical practice and research field of AIT. This article reviewed the relevant progress of the mechanism, efficacy and drug administration of AIT.

Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes / 解剖学报

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Visualization analysis of magnetically controlled growing rod in treatment of spinal deformities / 中国组织工程研究

BACKGROUND:With the continuous improvement and progress of the magnetically controlled growing rod technology in the field of the treatment of spinal deformities,numerous studies have been put into this field,but the main research status,hot spots,and development trends are not clear enough. OBJECTIVE:Based on bibliometrics,this paper discusses the quality and quantity of articles in the field of using magnetically controlled growing rods to treat spinal deformities from different countries,aiming to clarify the global development trend of magnetically controlled growing rods and evaluate the research productivity,research trends,and research hotspots in the world. METHODS:The articles published from 1998 to 2023 were retrieved mainly based on the Web of Science database.CiteSpace 5.8 and VOSviewer 1.6.19 software were used to analyze the data and generate a visual knowledge map.The following parameters were evaluated for all studies:the total number of published papers,centrality,h index,the contribution of countries,authors,and journals,and the trend and hot spots were explored through the analysis of co-citation,highly cited literature,and literature keyword explosion. RESULTS AND CONCLUSION:(1)Finally,138 articles were included.From 2009 to 2020,the number of published articles in this field gradually increased.The United States has the largest number of articles(53,37.32%),and the United States has the highest h index and centrality of articles.(2)The results of keyword analysis showed that:the top ten keywords,such as early-onset scoliosis,surgery,complications,and so on,objectively and truly reflected the current situation and hot spots of magnetically controlled growing rod in the field of spinal deformity treatment.In recent years,the research focus in this field is the treatment failure caused by risk factors such as the pull-out of the magnetically controlled growing rod,implantation failure,and rod fracture,the accurate use of the corresponding medical classification,the monitoring and treatment of complications such as quality of life and cerebral palsy.(3)The co-citation results showed that:combined with the innovative and effective research of the magnetically controlled growing rod technology,the classification application of spinal deformity and the monitoring and treatment of related complications may be the research trend in this field.(4)Many highly cited articles further emphasized the therapeutic effect of magnetically controlled growing rod technology,providing an effective new idea and technical support for the field of spinal deformity correction.(5)The results of literature keyword explosion analysis demonstrate that the risk factors,medical classification,quality of life,and cerebral palsy of the application of magnetically controlled growing rods may become the research frontier in this field.(6)It can be seen that the application of magnetically controlled growing rod technology in the classification of spinal deformities and the in-depth study of related complications are the development trend in this field,but to further understand the effectiveness and safety of magnetically controlled growing rod technology in the treatment of spinal deformities,we still need long-term follow-up evidence.The overall research level of this field has steadily improved in recent years,but there are also problems such as the small number of high-quality articles and the unbalanced development of research in various regions.

Characteristics and significance of age-related changes in cervical uncinate process-related angle / 中国组织工程研究

BACKGROUND:As a unique structure of the cervical spine,the occurrence,development and progression of the uncovertebral joint directly affect the stability and range of motion of the cervical spine,and are also closely related to the pathogenesis of cervical spondylosis.A thorough understanding of the developmental characteristics of the uncovertebral joint is of great significance for the pathogenesis,diagnosis,and treatment of cervical spondylosis. OBJECTIVE:By using imaging and three-dimensional reconstruction technology to measure and observe the cervical uncinate process-related angle in a large sample of different age groups,the aim is to reveal the characteristics of its changes with age and vertebral growth,as well as its relationship with cervical spine stability. METHODS:Using a retrospective research design,we collected 1 447 cases of raw CT imaging data that meet the study requirements for complete cervical spine segments.The raw data were imported into Mimics 21.0 software in DICOM format for post-processing and measurement of angle of uncinate process and sagittal angle of uncinate process.The data were grouped based on gender,age,and side. RESULTS AND CONCLUSION:(1)With the increase of vertebral sequence,the angle of uncinate process increased in a V-shaped shape,and the lowest peak was at C5.The overall population showed a sharp peak with the increase of age,and the peak value mostly occurred in the age range of 30-39 years.(2)The sagittal angle of the uncinate process increased like a fishhook with the increase of the vertebral sequence,and the overall angle of the uncinate process increased with age,and the peak value mostly occurred in the age range of 20-29 years.The uncinate process angle and sagittal angle showed only partial significant differences between sides and genders(P<0.05).(3)It is concluded that the angle of the uncinate process increased with the increase of vertebral sequence in a V-shaped manner.The sagittal angle of the uncinate process increases like a fish hook with increasing vertebral order,while the two angles generally peak with increasing age.The angle of the uncinate process is about 131°,which may be closely related to the stability of the cervical spine,while the sagittal angle of the uncinate process is about 14°,and its function may play a certain role in limiting the excessive rotation of the cervical spine.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin.@*METHODS@#A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43.@*RESULTS@#The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43.@*CONCLUSIONS@#The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Macroscopic and mesoscopic biomechanical analysis of the bone unit in idiopathic scoliosis / 生物医学工程学杂志

To investigate the effects of postoperative fusion implantation on the mesoscopic biomechanical properties of vertebrae and bone tissue osteogenesis in idiopathic scoliosis, a macroscopic finite element model of the postoperative fusion device was developed, and a mesoscopic model of the bone unit was developed using the Saint Venant sub-model approach. To simulate human physiological conditions, the differences in biomechanical properties between macroscopic cortical bone and mesoscopic bone units under the same boundary conditions were studied, and the effects of fusion implantation on bone tissue growth at the mesoscopic scale were analyzed. The results showed that the stresses in the mesoscopic structure of the lumbar spine increased compared to the macroscopic structure, and the mesoscopic stress in this case is 2.606 to 5.958 times of the macroscopic stress; the stresses in the upper bone unit of the fusion device were greater than those in the lower part; the average stresses in the upper vertebral body end surfaces were ranked in the order of right, left, posterior and anterior; the stresses in the lower vertebral body were ranked in the order of left, posterior, right and anterior; and rotation was the condition with the greatest stress value in the bone unit. It is hypothesized that bone tissue osteogenesis is better on the upper face of the fusion than on the lower face, and that bone tissue growth rate on the upper face is in the order of right, left, posterior, and anterior; while on the lower face, it is in the order of left, posterior, right, and anterior; and that patients' constant rotational movements after surgery is conducive to bone growth. The results of the study may provide a theoretical basis for the design of surgical protocols and optimization of fusion devices for idiopathic scoliosis.

Association of circulating levels of soluble PD-1, PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma / 中华预防医学杂志

Objective: To investigate the association of circulating sPD-1 level and PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma. Methods: A case-control study was conducted. A total of 237 chronic HBV infection cases and 138 HBV infection-associated hepatocellular carcinoma in the Department of Infectious Diseases of the First Hospital of Shanxi Medical University from 2018 to 2021 were selected as the case group. About 250 individuals who visited a hospital physical examination center for routine physical examination during the same period were selected as the control group. Plasma sPD-1 levels were measured by using an ELISA kit and genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association of sPD-1 levels and PD-1 polymorphisms with HBV infection as well as HBV infection-associated hepatocellular carcinoma was analyzed by using logistic regression models after adjusting for age, sex, alcohol consumption, smoking, ALT and AST levels. The sPD-1 level and PD-1 polymorphisms were independent variables, and HBV infection was the dependent variable. Results: The age of 237 chronic HBV infections, 138 HBV infection-related liver cancer case subjects and 250 control subjects in the study was (49.1±10.8), (51.9±12.7) and (50.7±11.9) years, respectively. Multivariate logistic regression model analysis showed that with a 1 pg/ml increase in sPD-1 level, the OR (95%CI) values for the risk of incident HBV infection cases and HBV hepatocellular carcinoma cases were 1.92 (1.68-2.19) and 2.02 (1.69-2.40). For rs2227981, compared with the CC genotype, the TT genotype had a lower risk of HBV infection and liver cancer associated with HBV infection, with OR (95%CI) values of 0.45 (0.22-0.91) and 0.35 (0.14-0.91). For rs2227982, compared with the CC genotype, the CT and TT genotypes also had a lower risk of HBV infection [OR (95%CI) values of 0.72 (0.53-0.97) and 0.57 (0.35-0.93)] and HBV infection-related liver cancer [OR (95%CI) values of 0.64 (0.45-0.92) and 0.52 (0.29-0.93)]. Conclusions: Plasma sPD-1 levels and PD-1 gene polymorphisms are associated with HBV infection and HBV infection-associated hepatocellular carcinoma.

Effect of cervical Luschka joint degenerative change on expression of VEGF and its receptor / 局解手术学杂志

Objective To observe the effect of cervical degenerative change on the expression of vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor-2(VEGFR-2).Methods The C3 to C7 segments of bilateral healthy cervical vertebrae of adult cadavers were taken as the control group,and the C3 to C7 segments of bilateral degenerative cervical vertebrae of adult cadavers were taken as the experimental group.The expression changes of VEGF and VEGFR-2 of the two groups were observed and analyzed by immunohistochemistry,immunofluorescence staining and real-time quantitative PCR.Results The protein and mRNA expressions of VEGF and VEGFR-2 in the experimental group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Cervical Luschka joint degenerative change significantly up-regulates the expression of VEGF and VEGFR-2,which is closely related to the microenvironmental changes around the Luschka joint caused by degeneration of joint-like structure.

Effects of GSK484 on ventilator-induced lung injury and neutrophil extracelluar traps in mice / 中华麻醉学杂志

Objective:To evaluate the effects of GSK484 on ventilator-induced lung injury (VILI) and neutrophil extracelluar traps (NETs) in mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 5-6 weeks, weighing 15-20 g, were divided into 4 groups ( n=12 each) by a random number table method: spontaneous breathing group (group S), spontaneous breathing+ GSK484 intervention group (group SG), VILI group (group V), and VILI + GSK484 intervention group (group VG). The animals kept spontaneous breathing for 4 h after tracheal intubation in S and SG groups. The animals were mechanically ventilated for 4 h (tidal volume 30 ml/kg, respiratory rate 75 breaths/min, inspiratory/expiratory ratio 1∶2, positive end-expiratory pressure 0 mmHg, fraction of inspired oxygen 21%) in V and VG groups. At 3 days before developing the VILI model, GSK484 4 mg/kg was intraperitoneally injected once a day in SG and VG groups, while the equal volume of normal saline was given instead in S and V groups. Blood samples were collected from the abdominal aorta for blood gas analysis at 4 h of spontaneous breathing or mechanical ventilation, and PaO 2 was recorded. The mice were then sacrificed and bronchoalveolar lavage fluid (BALF) was collected and lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope after HE staining) which were scored and for determination of wet to dry weight ratio (W/D ratio), concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) in BALF (by enzyme-linked immunosorbent assay), expression of peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), high mobility group box 1 (HMGB1) and citrullinated-histone 3 (Cit-H3) in lung tissues (by Western blot). Results:Compared with S and SG groups, the lung injury score and W/D ratio were significantly increased, PaO 2 was decreased, concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 in lung tissues was up-regulated in V and VG groups ( P<0.05). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 was increased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group VG ( P<0.05). Conclusions:GSK484 can alleviate VILI in mice, and the mechanism is associated with inhibition of PAD4, reduction of the production of NETs and attenuation of inflammatory responses in lung tissues.

Correlation of serum albumin level at admission with clinical prognoses in patients with acute traumatic brain injury / 中华神经医学杂志

Objective:To explore the correlation of serum albumin level at admission with clinical prognoses in patients with acute traumatic brain injury (TBI).Methods:One hundred and fifty-four patients with acute moderate-extreme severe TBI (Glasgow Coma Scale [GCS] scores of 3-12 at admission) in Department of Neurosurgery, General Hospital of Western Theater Command from January 1, 2019 to December 31, 2020 were chosen. The comprehensive clinical data of these patients were collected, including age, gender, GCS scores, serum albumin level (hypoalbuminemia defined as<35 g/L), hemoglobin level, comorbidities, treatment measures, and prognoses 6 months after discharge (poor prognosis defined as Glasgow outcome Scale [GOS] scores of 1-2, and good prognosis defined as GOS scores of 3-5). Univariate and multivariate Logistic regressions were used to identify the independent factors for clinical prognoses of these patients, and differences in poor prognosis rate, length of ICU stay, and total hospital cost were compared between different groups.Results:Among the 154 patients, 43 had poor prognosis and 111 had good prognosis. Serum albumin level at admission ( OR=0.916, 95% CI: 0.843-0.996, P=0.001) and GCS scores at admission ( OR=0.701, 95% CI: 0.594-0.828, P<0.001) were independent factors for prognosis. Patients with hypoalbuminemia ( n=70) displayed significantly higher poor prognosis rate, longer ICU stays, and increased total hospitalization cost compared with those without hypoalbuminemia ( n=84, P<0.05); specifically, in patients with GCS scores of 9-12 at admission ( n=58), those with hypoalbuminemia ( n=27) exhibited significantly higher poor prognosis rate, longer ICU stays, and higher total hospitalization cost than their non-hypoalbuminemia counterparts ( n=31, P<0.05); similarly, in patients with GCS scores of 3-8 at admission ( n=96), those with hypoalbuminemia ( n=74) had significantly higher poor prognosis rate than their non-hypoalbuminemia counterparts ( n=22, P<0.05). In patients with good prognosis, those with hypoalbuminemia ( n=56) showed significantly longer total hospital stays, prolonged ICU stays, and increased total hospitalization cost compared with those without hypoalbuminemia ( n=55, P<0.05). Conclusion:Low serum albumin level at admission is likely to lead to poor prognosis, prolonged ICU stays and increased total hospitalization cost in patients with acute TBI.

Does Social Capital Promote Health?

The determinants of health are influenced by genetics, lifestyle, social environment, medical conditions, etc. As an informal system, social capital plays an increasingly recognized role in individual health. The purpose of this paper is to discuss the direct and indirect effects of social capital on individual health in China. Using cross-sectional data from the China Family Panel Studies 2016, this paper explores the effects of cognitive and structural social capital on individual health from a micro perspective. The results show that both types of social capital have significant positive effects on individual health, and this effect remains after endogeneity is considered. The two types of social capital show obvious heterogeneity in age samples, urban and rural samples and north-south samples. In addition, the mechanism analysis shows that the health promotion effects of the two types of social capital are mainly derived from the effects of informal finance and access to medical resources. Based on the above findings, this paper puts forward policy recommendations.

Macular morphology and vascular parameters changes following micro-invasive vitrectomy in patients with severe non-proliferative diabetic retinopathy / 中华眼底病杂志

Objective:To observe the changes of macular morphology and blood flow after minimally invasive vitrectomy (PPV) in patients with severe non-proliferative diabetic retinopathy (sNPDR).Methods:A prospective clinical study. From January 2020 to April 2021, 17 consecutive sNPDR patients with 17 eyes who were diagnosed and received PPV treatment at the Zhongshan Ophthalmic Center of Sun Yat-sen University were included in the study. There were 12 males with 12 eyes and 5 females with 5 eyes; the average age was 55 years old; the average duration of diabetes was 11 years; the average glycosylated hemoglobin was 7.9%. Before the operation and 1, 3, and 6 months after the operation, all the affected eyes underwent best corrected visual acuity (BCVA), standard 7-field fundus color photography, and optical coherence tomography angiography (OCTA). An OCTA instrument was used to scan the macular area of the affected eye with in the range of 3 mm×3 mm to measure the central subfoveal thickness (CST), the thickness of the ganglion cell complex (GCC) in the macular area, the thickness of the retinal nerve fiber layer (RNFL), and the superficial capillary plexus (SCP) vessel density and perfusion density in the macular area, macular avascular zone (FAZ) area, a-circularity index (AI). Before the operation and 6 months after the operation, the least significant difference test was used for the pairwise comparison.Results:Before the operation, 1, 3, and 6 months after the operation, the FAZ area of the macular area were 0.34±0.14, 0.35±0.10, 0.37±0.10, 0.36±0.13 mm 2, respectively; AI were 0.52±0.13, 0.54±0.11, 0.57±0.10, 0.60±0.11; CST was 282.6±66.7, 290.4±70.9, 287.2±67.5, 273.2± 49.6 μm; GCC thickness were 77.1±15.5, 74.3±13.9, 72.6±16.2, 78.5±18.3 μm; the thickness of RNFL was 97.9±13.8, 101.3±14.6, 97.7±12.0, 96.1±11.4 μm, respectively. The overall blood flow density of SCP in the macula were (16.79±1.43)%, (16.71±1.82)%, (17.30±2.25)%, (17.35±1.22)%; the overall perfusion density were 0.32±0.02, 0.32±0.03, 0.33±0.03, 0.33±0.02, respectively. After the operation, the CST increased first and then decreased; the thickness of RNFL increased 1 month after the operation, and then gradually decreased. Comparison of the parameters before and 6 months after the operation showed that the AI improved, and the difference was statistically significant ( P=0.049); the difference in FAZ area and the thickness of CST, GCC, and RNFL was not statistically significant ( P=0.600, 0.694, 0.802, 0.712); There was no statistically significant difference in the retina SCP blood flow density and perfusion density in the macular area ( P=0.347, 0.361). Conclusion:Compared with before surgery, there is no significant change in macular structure and blood flow density in sNPDR patients within 6 months after minimally invasive PPV.

The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells / 中华肿瘤杂志

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

Screening and analysis of prognostic factors of repairing single missing tooth by autotransplantation of teeth / 中华口腔医学杂志

Objective: To screen and analyze the factors affecting the prognosis of replacing single missing tooth by autograft tooth, so as to provide reference for clinical judgment of surgical prognosis. Methods: A total of 176 patients (188 teeth) underwent autotransplantation of teeth in the Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University from January 2017 to December 2019, including 85 teeth of males and 103 teeth of females were involved. The age was (33.0±9.8) years (16-65 years). The possible factors affecting the prognosis of replacing single missing tooth by autograft tooth were summarized and grouped, and the clinical and imaging data were recorded and judged. The surgical records and photographic data from the patients' previous medical records were retrospectively analyzed. The survival analysis method was used for statistical analysis to screen out the factors affecting the cumulative survival rate of transplanted teeth. Results: The 5-year cumulative survival rate of 188 transplanted teeth was 88.4%. Univariate Log-Rank analysis showed that age (P<0.001), sex (P=0.008), smoking (P<0.001), position of recipient area (P<0.001), height of alveolar bone in recipient area (P<0.001), time of donor tooth in vitro (P<0.001), use of donor model (P<0.001) and initial stability (P<0.001) were significantly correlated with cumulative survival rate of transplanted teeth. Multivariate Cox proportional hazard regression analysis showed that smoking (β=-2.812, P=0.049), alveolar bone height (β=1.521, P=0.020), donor time (β=-2.001, P=0.019), use of donor model (β=1.666, P=0.034) and initial stability (β=-1.417, P=0.033) were significantly correlated with the cumulative survival rate of transplanted teeth. Conclusions: The prognosis of autogenous tooth transplantation can be predicted by smoking, height of alveolar bone in recipient area, time of donor teeth in vitro, use of donor model and initial stability. Good prognosis of transplanted teeth can be obtained by using donor model during operation, reducing the time of donor teeth in vitro, taking effective methods to restore alveolar bone height, maintaining good initial stability, and good oral health education after operation.