Objective To study the effects of intramedullary pressure on the fluid flow behavior in bones.Methods Multi-scale models of macro bone tissue and macro-meso osteon groups were established using the COMSOL Multiphysics software.Considering the interrelationship of different pore scales,such as the bone marrow cavity,Haversia canal,and bone lacunar-canaliculus,the pore pressure and flow rate of hollow bone tissues and bone tissues with intramedullary pressure were compared,and the effects of the amplitude and frequency of intramedullary pressure on the pressure and flow velocity of the liquid in the bone were analyzed.Results When intramedullary pressure was considered,the pore pressure in bone tissues with intramedullary pressure was 6.4 kPa higher than that in hollow bone tissues.The flow pressure increased significantly with an increase in the intramedullary pressure amplitude,but the flow velocity remained unchanged.The frequency of intramedullary pressure had little effect on pore pressure and flow velocity.Conclusions The multi-scale pore model established in this study can accurately analyze bone fluid flow behavior.These results are of great significance for an in-depth understanding of force conduction in the bone.

Objective To investigate the protective effect of insulin-like growth factor-1(IGF-1)precondi-tioning on hypoxic injury in H9c2 rat cardiomyocytes and its mechanism.Methods H9c2 cells were randomly divided into four groups,control group,hypoxia group(CoCl2 group),hypoxia+IGF-1 pretreatment group(CoCl2+IGF-1 group),hypoxia+IGF-1 pretreatment+phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway specific inhibitor LY294002 group(CoCl2+IGF-1+LY294002 group).CCK8 assay was used to detect the survival rate of H9c2 cells,and Tunel assay was used to detect the apoptosis of H9c2 cells,DCFH-DA probe method was used to detect the reactive oxygen species(ROS)level of H9c2 cells in each group.The activities of superoxide dismutase(SOD)and lactate dehydrogenase(LDH)in culture supernatant were detected by kit.The levels of glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of pro-apoptotic protein B cell lymphoma 2 associated X protein(Bax),Caspase-3,anti-apoptot-ic protein Bcl-2,pathway proteins Akt and phosphorylated Akt(p-Akt)in H9c2 cells.Results IGF-1 could increase cell viability(P＜0.05),reduced cell apoptosis rate(P＜0.05),reduced ROS level(P＜0.05),re-duced MDA production(P＜0.05),reduced LDH activity(P＜0.05),and increased SOD and GSH-Px activi-ties(P＜0.05).It also promoted the expression of p-Akt(P＜0.05),reduced the expression of pro-apoptotic proteins Bax and Caspase-3(P＜0.05),and increased the expression of anti-apoptotic protein Bcl-2(P＜0.05).After the addition of PI3K pathway specific inhibitor LY294002,the protective effect of IGF-1 on hy-poxic H9c2 cells disappeared.Conclusion IGF-1 protects cardiomyocytes from hypoxia injury by inhibiting oxidative stress and apoptosis of cardiomyocytes through activating PI3K/Akt pathway and improving the survival rate of cardiomyocytes.

Although the artificial intelligence diagnosis technology of traditional Chinese medicine(TCM)is constantly developing,the existing intelligent syndrome differentiation models can only output the diagnosis results and cannot display the reasoning process of TCM diagnosis.They do not have the interpretability of TCM diagnostic knowledge and are difficult to truly reflect the process of TCM's syndrome differentiation.This can be a long-standing problem that has puzzled the academic community.This article elaborates on the development process and technical characteristics of intelligent diagnosis in traditional Chinese medicine,explores multiple key technologies and bottlenecks in current research in reasoning of TCM's Syndrome Differentiation,and factors affecting diagnosis.A novel intelligent diagnosis model architecture that can infer and explain the process of TCM'ssyndrome differentiation was proposed,and the implementation process of the model and algorithm was explained,and detailed data instance analysis was conducted.This article will provide new methods for the development of intelligent syndrome differentiation of TCM and open up new research ideas for clinical decision-making assistance of TCM.

Background: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Due to the COVID-19 pandemic, the teaching of Biopharmaceutical Engineering course was carried out online and completed with satisfactory outcomes. In order to improve the efficiency of online teaching, ensure the substantive equivalence between online and offline teaching and achieve effective teaching, this article summarized the exploration and practical experience of online teaching, taking the Biopharmaceutical Engineering course as an example. This includes analysis of learner characteristics, selection of online teaching platform, development of teaching resources, optimization of teaching contents, BOPPPS teaching method-based design of teaching structure, and reflection of effective teaching. This paper is expected to provide a useful reference for online teaching.
Humans ; Biological Products ; Pandemics ; COVID-19

The pathogenesis of neovascular age-related macular degeneration (nAMD) is complex and macular neovascularization (MNV), a key pathogenic factor in nAMD, is prone to recurrence.Vitreous injection of anti-VEGF drugs is the main therapy of nAMD.In recent years, a lot of progress has been made in fundus imaging techniques and optical coherence tomography angiography (OCTA) with non-invasive, rapid, stratified and high-definition functions has shown strong advantages in diagnosis, differential diagnosis, disease dynamic monitoring and follow-up of nAMD.Clinicians have had a certain understanding of the important role of OCTA in the diagnosis of nAMD and other diseases, and its clinical application value has been recognized gradually.However, its application value in follow-up of patients with nAMD and polypoid choroidal vasculopathy (PCV) is still not well understood.By reviewing a large number of recent relevant literature on OCTA, and combining the clinical practice of our research team in monitoring the course of AMD and PCV disease by OCTA, we have gained new knowledge and understanding of the pathological mechanism of AMD and PCV.In this paper, we elucidated the latest understanding of the diagnostic value of OCTA in AMD based on long-term series of OCTA studies, the new findings of OCTA in AMD management of our team, as well as its impact on ophthalmology clinical practice.Then we forecasted the role of OCTA in the prediction of recurrence and anti-VEGF treatment response, as well as the clinical value of OCTA in the optimization of nAMD treatment and follow-up plan.It is recommended that clinicians pay more attention to the clinical value and guiding role of OCTA in long-term treatment monitoring and follow-up of AMD.

Objective BALB/c mutant curly mice and normal BALB/c mice were genetically detected by microsatellite DNA marker analysis to detect the differential microsatellite loci between BALB/c mutant curly mice and normal mice.Methods 38 microsatellite DNA loci were selected and their variation in the BALB/c mutant curly mice, BALB/c mutant hairless mice and normal BALB/c mice were detected by multiplex fluorescence PCR and STR scanning genotyping.Results There were 27 the same microsatellite loci between the 38 microsatellite loci in BALB/c mutant curly mice and normal mice,and there were 11 differential loci, with a mutation rate of 28.9%(11/38). There were 30 the same sites between BABL/c mutant hairless mice and normal mice,and there were 8 different loci,with a mutation rate of 21.1%(8/38). There were also 12 differential loci between BABL/c mutant curly mice and hairless mice. Conclusions BALB/c mutant curly mice have a higher mutation rate and are significantly higher than those of hairless mice,demonstrating that the mutations in curly mice and hairless mice are two completely different mutations. These results provide reliable theoretical data for the future study and development of BALB/c mutant curly mice.