Objective To study the use of phospholipase A2(PLA2)to open blood brain barrier(BBB)by affecting the physiological barrier function and promote the antidote drug asoxime(HI-6)to take effect in brain,providing a new research idea for the treatment of central nervous system organophosphorus poisoning.Methods The stability of the complex of PLA2-HI-6 was characterized through methods such as release and stability experiments.The cerebral delivery ability of the complex was evaluated through brain tissue FLU fluorescence pathology.The effect of PLA2 on cell membrane permeability was evaluated by observation with propidium iodide(PI)staining.The mouse model of soman poisoning was established to evaluate cerebral effects of the complex against soman central poisoning:(1)measuring the reactivation rate of mouse brain acetylcholinesterase(AChE);(2)observing pathological sections of mouse brain tissues;(3)calculating the survival time of mice in different groups.The safety of PLA2 was evaluated at both cellular and animal levels.Results Releasing and stability test results showed that the addition of PLA2 didn't affect the release and degradation of HI-6.PLA2 helped FLU transport into brain tissues,demonstrating excellent central delivery capability.The complex of PLA2-H1-6 significantly increased the reactivation rate of AChE in the brain of poisoned mice to 50％,about 12 times higher than that treated by HI-6 alone.Pathological results of mouse brain tissue showed that the complex effectively counteracted the cerebral nervous system damage caused by organophosphorus poisoning,significantly prolonged the survival time of mice at three times the lethal dose,and significantly alleviated symptoms of central toxicity.Research on delivery mechanisms found that complex achieved central delivery by increasing the permeability of the cell membrane to crossing the cell.Safety tests at the cellular and animal levels showed that the dosage of PLA2 used in this study was safe and reliable,and did not cause any adverse reactions.Conclusion By using PLA2 as an open material,combined with the therapeutic drug of HI-6,a complexcapable of effectively penetrating the BBB was successfully constructed.This complex has a certain central targeting ability and significantly improves the reactivation rate of AChE in the brain after organophosphorus poisoning,whichprovides a referencefor solving the difficult problem of enzyme reactivation incentral nervous system organophosphorus poisoning.

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP⁺ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.

Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.
Humans ; DNA Copy Number Variations ; Nuclear Proteins/genetics* ; Central Nervous System Neoplasms/pathology* ; Transcription Factors/genetics* ; Prognosis ; Lymphoma/genetics* ; Genomics ; China ; Central Nervous System/pathology* ; Bromodomain Containing Proteins ; Cell Cycle Proteins/genetics*

Purpose To explore the association of tumor budding in preoperative biopsies with the clinicopathological characteristics of colorectal cancer(CRC),and its effects on the prognosis.Methods A total of 144 preoperative biopsies and corresponding radical resection specimens of colorectal ade-nocarcinoma were collected.Tumor budding was evaluated by HE staining and EnVision immunohistochemical staining,to an-alyze the association of tumor budding with the clinicopathologi-cal characteristics and prognosis in biopsies.Results The de-tection rate of intra-tumoral budding(ITB)in biopsy specimens was 39.6%(57/144),and peritumoural budding(PTB)in surgical specimens was 64.6%(93/144);ITB was significantly correlated with PTB(r =0.510,P<0.05).The proportion of patients with lymph node metastasis,pTNM stage,differentiated degree,vascular invasion and nerve recidivism in the tumor bud-ding group of biopsies was significantly higher than that in no tumor budding group(P<0.05).Kaplan-Meier survival analy-sis showed that ITB significantly affected the overall survival and progression free survival of CRC(P<0.05).Conclusion The presence of ITB in biopsies tissue may be an important indicator of invasive behavior and poor prognosis in CRC.

Objective:To establish a multi-component exercise intervention program for the elderly with frailty, assess its effectiveness on improving the severity of frailty, and examine the effects of different intervention modes.Methods:174 elderly people in a community in Beijing were randomly divided into three groups.The control group did not receive special intervention.The health education group received lectures, demonstrations and pamphlets on basic knowledge about frailty and instructions about a multi-component sports program.The multi-component exercise training program group was trained for three months via regular videos delivered through a WeChat app.The severity of frailty and exercise adherence of subjects in the three groups were compared.Results:166 subjects completed the study.Frailty phenotype(FP)scores of the health education group and the WeChat app group were lower than those at baseline( P<0.05).After intervention, FP scores of the control group, the health education group and the WeChat app group were 1(1, 2), 1(0, 1)and 1(0, 1), respectively, and there were differences among the three groups after intervention( H=15.539, P<0.05).There were 10 subjects(17.2%)in the control group, 15(25.9%)in the health education group and 28(48.3%)in the WeChat app group who experienced reversal from frailty or pre-frailty to no frailty( χ2=12.770, P=0.002).The number of people who reversed to no frailty in the WeChat app group was higher than in the control group( χ2=11.536, P=0.001)and the health education group( χ2=5.659, P=0.014).The numbers of people with frailty in the control group, health education group and WeChat app group were 9(15.5%), 1(1.7%)and 1(1.7%), respectively( χ2=13.040, P=0.001), with the numbers of frailty cases in the health education group and the WeChat app group lower than in the control group( χ2=7.552, 7.210, P=0.006, 0.007).The percentage of people completing the exercise program in the WeChat app group was higher than in the control group( χ2=49.366, P<0.001)and also in the health education group( χ2=26.481, P<0.001), while the percentage of people completing the exercise program in the health education group was higher than in the control group( χ2=6.171, P=0.013). Conclusions:The multi-component exercise program can improve the frailty state of the elderly, and the intervention method based on the WeChat app has clear advantages in improving frailty and enhancing exercise adherence.

With the acceleration of aging process and the increase of average life in China, the number of disabled elderly in China is also growing rapidly, which undoubtedly brings a heavy care burden and pressure to families and society.Facing the great challenges brought by aging, the increasing evidences show that only by reducing the incidence of disease and disability from the source, improving the health level of the elderly, prolonging their healthy life and realizing healthy aging, we can fundamentally alleviate the great pressure brought by the aging society.The concept of motor function maintenance and health promotion of the elderly has become an important link and breakthrough to realize healthy aging and active health.Facing the requirements of active health medicine and the development trend of science and technology in the future, it is imperative to deeply study the motion characteristics and function maintenance of the elderly, and promote the development of sports medicine with innovative technologies such as internet, big data and artificial intelligence.In the future, we will continue to improve the assessment and maintenance system for motor function of the elderly, develop and optimize functional maintenance products that meet the exercise needs of the elderly, and actively build an elderly-friendly sports environment support system, thereby promoting the healthy China strategy and realize healthy aging to the greatest extent.

Objective:To investigate the techniques used in blood flow control of Kimura laparoscopic spleen-preserving pancreatectomy (LSPDP).Methods:Forty·five patients with benign or low-grade malignant pancreatic diseases undergoing LSPDP at Huzhou Central Hospital from May 2014 to Oct 2021 were analyzed retrospectively. Patients were divided into splenic vascular flow control group ( n=22) and routine management group ( n=23). Results:There was no significant difference in gender, age, BMI, accompanying symptoms, hypertension, diabetes, lesion size and pathological diagnosis between the two groups (all P>0.05). A higher overall spleen preservation rate (90.9% vs. 52.2%, χ2=8.213, P=0.004), lower incidence of morbidity with Clavien grade ≥ Ⅱ (22.7% vs. 73.9%, χ2=9.911, P=0.002) and shorter postoperative hospital stay [(9.6±4.5) d vs. (14.3±6.6) d, t=2.447, P=0.008] were achieved in the vascular flow control group compared with those in the routine group. Conclusion:Splenic vascular flow control techniques improve the success rate of spleen preservation in laparoscopic distal pancreatectomy, reduce the postoperative complications and shorten the postoperative hospital stay.

Objective:To investigate the effect of slow intravenous infusion of low-dose mannitol on the hemodynamics of patients after cardiopulmonary bypass.Methods:Prospective, continuous inclusion of 62 patients after cardiac surgery under cardiopulmonary bypass. By random number method, they were divided into normal treatment group(group C) with 29 cases and mannitol treatment group(group M) with 33 cases. Group C was treated according to the postoperative routine treatment measures. On the basis of conventional treatment, group M received intravenous infusion of 20% mannitol injection 0.25 g/kg at 1、8、24 hours after operation, and the intravenous infusion time was 60 minutes each time. According to the hemodynamic changes during the two groups of treatment, the effect of slow intravenous infusion of low-dose mannitol on patients after cardiopulmonary bypass under cardiopulmonary bypass was analyzed.Results:In group M, CI and SVI were significantly increased after use of mannitol than before, with statistical significance( P<0.01). SVRI showed a downward trend, and the changes were statistically significant after use of mannitol( P<0.01). PAWP increased first and then decreased after operation, and the changes were statistically significant after mannitol use than before( P<0.05). RAP and MPAP had no significant changes after the first use of mannitol, but the changes after the latter two use mannitol were statistically significant than before( P<0.05). Repeated-measurement data analysis of variance was performed on the hemodynamic parameters of each group, and the results were all P<0.01. Conclusion:Postoperative slow intravenous infusion of low-dose mannitol optimizes hemodynamic status, increases stroke volume, reduces cardiac preload, improves systemic and pulmonary circulation resistance, and promotes recovery of postoperative cardiopulmonary function.

Objective:To investigate the level of intrinsic capacity in community-dwelling elderly people and the influencing factors, in order to provide supporting evidence for the improvement of intrinsic capacity, formulation of management strategies, and promotion of quality of life for the elderly.Methods:A cross-sectional survey was carried out from November 2020 to December 2020 with 236 community-dwelling elderly people in Beijing, who were recruited through a convenience sampling method.The investigation used questionnaires for general data and influencing factors for intrinsic capacity, and the World Health Organization intrinsic capacity questionnaire.Multivariate logistic regression was used to analyze the influencing factors for intrinsic capacity of the elderly.Results:Among 236 community-dwelling elderly people, 132(55.9%)had fair intrinsic capacity(≥4 points)and 104(44.1%)had poor intrinsic capacity(<4 points), with an average score of(3.39±0.95). Multiple Logistic regression analysis results showed that sex( OR=2.005, 95% CI: 1.093-3.676, P=0.025), age( OR=1.727, 95% CI: 1.043-2.860, P=0.034), social participation( OR=0.321, 95% CI: 0.170-0.604, P<0.001), entertainment( OR=2.073, 95% CI: 1.079-3.985, P=0.029), exercise( OR=2.975, 95% CI: 1.761-3.784, P=0.039), sleep( OR=0.508, 95% CI: 0.265-0.973, P=0.041), and emotions( OR=0.436, 95% CI: 0.196-0.970, P=0.042)were influencing factors for intrinsic capacity of community-dwelling elderly people. Conclusions:The intrinsic capacity of community-dwelling elderly people is in the middle range.Sex, age, social participation, entertainment, exercise, sleep, and emotions can affect intrinsic capacity.Therefore, intervention strategies based on influencing factors and improvement of lifestyles can help maintain good intrinsic capacity and reduce adverse effects of major health events.