BACKGROUND:The plantarflexor weakness is a common muscle defect in patients with spastic cerebral palsy and Charcot-Marie-Tooth,which clinically manifests abnormal gaits,and the relationship between plantarflexor weakness and abnormal gaits is unclear. OBJECTIVE:To explore the biomechanical behavior of the lower limb under the action of a single factor of plantarflexor weakness to reveal the mechanism of abnormal gait induced by plantarflexor weakness and to provide guidance for the rehabilitation training of patients with plantarflexor weakness. METHODS:A predictive framework of musculoskeletal multibody dynamics in the sagittal plane was established based on OpenSim Moco to predict lower limb joint angles and muscle activation changes during walking in normal subjects.The validity of the framework was verified by combining the inverse kinematics and electromyogram activation time of the experimental data.Reduced isometric muscle forces were used to model plantarflexor weakness and to compare predicted lower extremity joint angles,joint moments,and muscle energy expenditure with normal subjects to analyze the effects of plantarflexor weakness on lower extremity biomechanics. RESULTS AND CONCLUSION:(1)The Moco-based prediction framework realistically predicted the biomechanical changes of the lower limbs during walking in normal subjects(joint angles:normalized correlation coefficient≥0.73,root mean square error≤7.10°).(2)The musculoskeletal model used a small stride support phase to increase the"heel-walking"gait during plantarflexor weakness.When the plantarflexor weakness reached 80%,the muscle energy expenditure was 5.691 4 J/kg/m,and the maximum activation levels of the gastrocnemius and soleus muscles were 0.72 and 0.53,which might cause the plantarflexor weakness patients to be more prone to fatigue when walking.(3)Muscle energy expenditure was significantly higher when the weakness of plantarflexors exceeded 40%,and the joint angles and moments of the lower limbs deteriorated significantly when the weakness of plantarflexors exceeded 60%,suggesting that there may be a"threshold"for the effect of plantarflexor weakness on gait,which may correspond to the point at which health care professionals should intervene in the clinical setting.

OBJECTIVE To systematically evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists(GLP-1RA) in the renal protection of type 2 diabetes(T2DM) patients, and provide evidence for clinic. METHODS Computer retrieval of PubMed, Embase, The Cochrane Library, Clinical Trials.gov, CNKI, WanFang Data and VIP databases, and manual retrieval of the included references. Randomized controlled trials(RCTs) for T2DM using GLP-1RA alone or GLP-1RA in combination with other conventional agents(experimental group) versus conventional treatment without GLP-1RA or placebo(control group). The search period spanned from the establishment of the database to January 30, 2022. Meta-analysis of the included data was performed using RevMan 5.4 statistical software. RESULTS A total of 7 studies were included, including 7 985 cases in experimental group and 6 633 cases in control group. Meta-analysis showed that the experimental group significantly reduced the incidence of renal complex endpoint events[Z=2.17, P=0.03, RR=0.79, 95%CI(0.64, 0.98)], urinary albumin creatinine ratio[Z=11.66, P<0.00001, MD=–23.74, 95%CI(–27.73, –19.74)], incidence of new macroalbuminuria[Z=5.79, P<0.000 01, MD=0.76, 95%CI(0.69, 0.83)], hemoglobin A1c[Z=12.76, P<0.000 01, MD=–0.94, 95%CI(–1.09, –0.80)] and estimated glomerular filtration rate[P=0.0007, Z=3.39, MD=–7.37, 95%CI(–11.63, –3.10)], the differences were statistically significant. One study showed that the experimental group could significantly reduce 24-hour urinary albumin excretion rate. However, there was no significant difference in the incidence of acute renal failure between the two groups[Z=0.63, P=0.53, MD=1.13, 95%CI(0.78, 1.63)]. In terms of safety, except the incidence of hypoglycemia, the incidence of adverse reactions in the experimental group was higher than that in the control group, including diarrhea, nausea, vomiting and loss of appetite, with statistically significant differences. CONCLUSION Existing research evidence shows that the common adverse reactions of GLP-1RA are gastrointestinal reactions and can be tolerated. Compared with placebo or conventional treatment without GLP-1RA, GLP-1RA may have a protective effect on the kidney of T2DM patients, and this conclusion needs to be further verified by RCTs.

Objective:To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province.Methods:Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty.Results:A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (a OR=1.55,95% CI: 1.07-2.25, P=0.019). In island area, older age (60-74 years:a OR=2.52,95% CI: 1.56-4.13; ≥75 years:a OR=11.65,95% CI:5.38-26.70), being women (a OR=1.94,95% CI: 1.20-3.17), suffering from depression (a OR=1.09,95% CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: a OR=1.74,95% CI:1.04-2.94;≥75 years: a OR=4.78,95% CI:2.45-9.50). Polydrug use (a OR=2.08,95% CI: 1.14-3.80) and suffering from depression (a OR=1.10,95% CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: a OR=0.40,95% CI: 0.21-0.75; senior high school and technical secondary school: a OR=0.29,95% CI: 0.15-0.53; college or above:a OR=0.22,95% CI: 0.11-0.42). Conclusions:The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.

Objective:To investigate effect of Gehua Jiecheng Decoction on IL-6/JAK2/STAT3 signaling pathway in colon tissue of ulcerative colitis with"inflammatory to cancer transformation"(UC-UCAC)mice of spleen deficiency and damp-heat type.Methods:Ten from 80 SPF C57BL/6 male mice were randomly selected as blank group and other 70 mice were selected as model group.After establishment of spleen deficient damp-heat model,mice were randomly divided into model group(1st,2nd and 3rd cycle),Gehua Jiecheng Decoction high,medium and low doses groups and mesalazine group,with 10 pieces per group.UC-UCAC transformation model was further established with azo methane oxide solution(AOM)/sodium glucan sulfate(DSS).Each group was treated with corresponding drugs for 4 weeks.General state of mice was observed.Score of disease activity index(DAI)was calculated.HE staining was used to observe colonic mucosa pathology of mice.EGFR,IL-6,JAK2,STAT3 and p-STAT3 proteins and genes expressions in mice colon tissues were detected by Western blot,IHC and RT-qPCR,respectively.Results:Compared with blank group,mice in model group(3rd cycle)were generally in a worse state,colon mucosal tissue was cancerous,DAI score,target proteins and genes expressions were significantly increased(P<0.01).Compared with model group(3rd cycle),general state of mice in all treatment groups were restored and colonic tissues pathology were improved to some extent.Target proteins and genes expressions in other treatment groups were significantly decreased except for Gehua Jiecheng Decoction low-dose group(P<0.01).Conclusion:Gehua Jiecheng Decoction may destroy tumor inflammatory microenvironment,repair damaged colonic mucosa tissue,delay inflamma-tion-cancer transformation process and prevent UCAC by inhibiting activation of IL-6/JAK2/STAT3 signaling pathway.

【Objective】 To study the effect of macrophage mediator 1 (MED1) deficiency on atherosclerosis in female mice. 【Methods】 ApoE knockout (ApoE^-/-), LDLR knockout (LDLR^-/-), MED1^fl/fl, and macrophage MED1 knockout (MED1^△Mac) mice were recruited in the study. Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout (MED1^△Mac/ApoE^-/-) mice and their littermate controls (MED1^fl/fl/ApoE^-/-). ② LDLR knockout (LDLR^-/-) mice receiving bone marrow from MED1^△Mac (MED1^△Mac→LDLR^-/-) or MED1^fl/fl (MED1^fl/fl→LDLR^-/-) mice. Female mice from these two models were fed a Western diet (21% fat and 0.15% cholesterol) for 12 weeks to promote the development of atherosclerosis. Body weight, total cholesterol (TC), and total triglyceride (TG) content in plasma were measured dynamically. After Western diet feeding for 12 weeks, aortic tree and aortic root were collected and hematoxylin-eosin (H&E) and oil red O staining were performed. 【Results】 Plasma TC and TG did not significantly differ between MED1^fl/fl/ApoE^-/- control group and MED1^△Mac/ApoE^-/-experimental group. However, the plaque area in aortic tree and aortic root was significantly increased in MED1^△Mac/ApoE^-/-mice. Moreover, compared with that in MED1^fl/fl→LDLR^-/- control group, the plaque area of aortic tree and aortic root had an increasing trend in MED1^△Mac→LDLR^-/- mice group. 【Conclusion】 MED1 deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

Objective:To analyze the clinical epidemiological characteristics and the prognostic risk factors of patients with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 2 245 HFRS patients who were admitted to the Second Affiliated Hospital of Air Force Medical University from September 2008 to December 2021 were enrolled. Clinical epidemiological data (including gender, age, onset season, onset region, case fatality rate, et al) of HFRS patients were analyzed. The clinical epidemiological characteristics of patients with HFRS in the 2008 to 2012, 2013 to 2017, and 2018 to 2021 groups were compared. Statistical comparisons were performed using chi-square test. The Bonferroni adjusted P-value method was used for pairwise comparisons between groups, and logistic regression analysis was used to screen and evaluate the risk factors associated with the prognosis of HFRS patients. Results:The age of 2 245 HFRS patients was (42.3±15.9) years old. Most of them were male (79.24%(1 779/2 245)), and the main incidence area was Xi′an City (69.53%(1 561/2 245)). There were 132 deaths with an overall case fatality rate of 5.88%. There were 1 088 patients (48.46%) from 2008 to 2012, 647 patients (28.82%) from 2013 to 2017, and 510 patients (22.72%) from 2018 to 2021, with a mortality rate of 7.17%(78/1 088), 5.10%(33/647) and 4.12%(21/510), respectively. From 2008 to 2021, both the number of HFRS cases and the case fatality rate had shown a fluctuating downward trend. There were significant differences in case fatality rate, age distribution, onset season, and onset region among patients in the different year groups ( χ2=6.84, 49.22, 83.47 and 19.29, respectively, all P<0.05). The results of pairwise comparisons showed that the proportion of patients aged >60 years in the 2018 to 2021 group (23.33%(119/510)) was higher than those in the 2008 to 2012 group (12.13%(132/1 088)) and the 2013 to 2017 group (12.36%(80/647)), and the differences were statistically significant (both P<0.05). The proportions of patients at large peak (October to December) were 62.35%(318/510) in the 2018 to 2021 group and 56.26%(364/647) in the 2013 to 2017 group, which were both lower than that in the 2008 to 2012 group (75.18%(818/1 088)), and the differences were both statistically significant (both P<0.05). The case fatality rate of patients aged >60 years was 9.67%(32/331), which was higher than those of patients aged <30 years (2.86%(16/559)) and patients aged 30 to 60 years (6.20%(84/1 355)), with statistically significant differences (both P<0.05). Univariate analysis showed that age 30 to 60 years, age >60 years, smoking, complicated with hypertension, hypotensive shock and hypoxemia were significantly correlated with the prognosis of HFRS patients (odds ratio ( OR)=2.243, 3.632, 1.484, 3.532, 79.422 and 143.955, respectively, all P<0.05). The results of multivariate logistic regression analysis indicated that complicated with hypertension ( OR=2.467, P=0.004), hypotensive shock ( OR=11.658, P=0.001), and hypoxemia ( OR=67.767, P<0.001) were the independent risk factors affecting the prognosis of HFRS patients. Conclusions:The prevalence of HFRS has shown new changing characteristics from 2008 to 2021. The numbers of HFRS patients and the case fatality rates show a downward trend, and the proportion of HFRS patients aged >60 years increases. Complicated with hypertension, hypotensive shock and development with hypoxemia are the independent risk factors for the prognosis of HFRS.

Objective:To evaluate the effect of berberine (BBR) on morphine-induced activation of BV2 microglial cells.Methods:The BV2 microglial cells were divided into 3 groups ( n=12 each) using a random number table method: control group (C group), morphine group (Mor group)and morphine+ BBR group (Mor+ BBR group). The Mor group was treated for 24 h with a final concentration of 200 μmol/L morphine, while C group was treated for 24 h with an equal volume of PBS buffer. Mor+ BBR group was first treated for 2 h with a final concentration of 20 μmol/L berberine, followed by treatment with a final concentration of 200 μmol/L morphine for another 24 h. The viability of BV2 microglial cells was determined using the CCK-8 assay, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-10 in supernatant were measured using enzyme-linked immunosorbent assay, and the expression of CD86 and NF-κB proteins in microglial cells was detected using Western blot. Results:Compared with group C, the BV2 microglial cell viability and concentrations of IL-1β and TNF-α were significantly increased, the concentrations of IL-10 were decreased, and the expression of CD86 and NF-κB in microglial cells was up-regulated in Mor group ( P<0.05). Compared with Mor group, the BV2 microglial cell viability and concentrations of IL-1β and TNF-α were significantly decreased, the concentrations of IL-10 were increased, and the expression of CD86 and NF-κB in microglial cells was down-regulated in Mor+ BBR group( P<0.05). Conclusions:BBR can inhibit morphine-induced activation of BV2 microglial cells.

Objective:To analyze the treatment effect and drug resistance mutation of HIV-1 infected patients who changed to the second-line antiretroviral treatment regimen after they had developed drug-resistance with first-line antiretroviral treatment regimen in some areas of Sichuan Province.Methods:Using the cohort study method, the patients who had developed drug resistance with the first-line regimen were followed up for two years from 1 January 2019 to 31 December 2021.The changes of CD4 +T lymphocytes (CD4) counts and viral load (VL) at the endline and the detection of drug-resistant mutation sites were analyzed using the chi-square test. Multivariate logistic regression model was used to analyze the influencing factors of antiretroviral treatment effect in patients who had good compliance after switching to the second-line regimen. Results:A total of 737 patients were recruited. Among the cases with continuous good compliance, those who timely changed to the second-line regimen had higher proportion of maintaining continuous CD4 >200 cells/μl and sustained virus inhibition ( P<0.05). Among the patients with different levels of drug resistance at baseline, there was no significant difference in continuous CD4 >200 cells/μl and sustained VL <200 copies/ml ( P>0.05). After changing to the second-line regimen, the drug-resistant mutation sites of some protease inhibitors showed an upward trend, while those of the non-nucleoside reverse transcriptase inhibitors showed a downward trend ( P<0.05). Multivariate logistic regression analysis showed that, among patients who had good compliance and who had switched to the second-line regimen, mother-to-child-transmitted patients had 3.01 times higher risk than heterosexual sexually transmitted infection (95% CI:1.29-7.00), failure to change the second-line protocol in time brought 2.55 times higher risk than that of timely changing to the second-line regimen (95% CI:1.41-4.62) and patients who infected with CRF85_BC subtype had 3.32 times higher risk than those infected with CRF01_AE subtype (95% CI:1.49-7.42). Conclusions:Difference in the drug resistance levels with the first-line regimen does not affect patients' antiretroviral treatment effect after changing to the second-line regimen in Sichuan Province. Changing to the second-line regimen in time and maintaining good compliance are beneficial to higher immune levels and lower VLs in drug-resistant patients. Among patients who changed to the second-line regimen, mother-to-child transmission, failure to change the second-line program in time, and infection with CRF85_BC virus are risk factors endangering antiretroviral treatment success after changing to the second-line regimen.

SMART (S = Specific, M = Measurable, A = Attainable, R = Relevant, T = Time-bound) principle is a goal-setting theory that includes five aspects: clarity, measurability, achievability, relevance, and timeliness. This online nutrition practice course introduces SMART principle teaching methodology to help students build autonomous learning capabilities. Questionnaires were used to learn about students' satisfaction. We also evaluated the students' practical skills by measuring students' self-perception of collaborative attitude, leadership, communication skills and intellectual challenge abilities before and after the course. The results found that 89.7% (26/29) of the students were generally satisfied with this online nutrition practice course. About 86.2% (25/29) of the students thought online learning was acceptable. By the end of the course, students' self-perception of collaborative attitude, leadership, communication skills and intellectual challenge abilities were increased by 7%, 13%, 14% and 10%, respectively. This online nutrition practice course indicates that SMART principle can help students build autonomous learning capabilities by setting practical, specific and time-limited teaching objectives, which improves students' learning enthusiasm and effectively enhances the practice ability of students.