BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Objective To investigate the allergen profiles of dust mite-sensitive allergic rhinitis patients in Dalian,and to lay the foun-dation for precise prevention and control of allergic rhinitis.Methods Clinical data of allergic rhinitis patients treated at Affiliated Zhongshan Hospital of Dalian University from January 2015 to December 2022 were collected.The allergen distribution spectrums were compared between different groups designated according to sex,age,allergen reaction level,combination of other allergens,and testing time.Results A total of 1 330 allergic rhinitis patients were included,among whom the total detection rate of dust mite allergy was 60.83%(n= 809),with 330(40.79%)of these having dust mite sensitization alone and 479(59.21%)having multiple sensitization.There were many kinds of allergens in multiple sensitization.Among those with dust mite allergy,all 20 combined allergens detected in this group were analyzed,and mugwort,cat hair,and common rinea grass were the top three allergens in combined sensitization,accounting for 64.52%.The number of other allergens combined with dust mite was mainly 1-3 species(88.73%),and a maximum of 10 allergens were simultaneously present.Patients with 1-3 other combined sensitivities were mainly reactive to respiratory allergens,and those with 4 or more allergens essentially had joint sensitization to respiratory and food allergens.As for the allergen reaction level,the dust mite sensitivity reaction was relatively strong,with grade 3 or above accounting for 61.19%.Except for mugwort,the other combined allergens elicited mainly grade 1 and grade 2 reactions.The detection rates of dust mite allergy were 61.84%in male patients and 59.94%in female patients,with no statistical difference between the sexes(χ2=4.000,P= 0.261).The detection rate of dust mite sensitization was highest in the group aged<20 years and decreased with age(χ2=69.984,P<0.001).Dust mite-sensitive allergic rhinitis mainly occurred from August to October,and the detection rate of dust mite sensitization was the highest in October,reaching 80.16%.Conclusion The dust mite sensitization rate in patients with allergic rhinitis in the Dalian area is relatively high,and multiple sensitization is more common.Combinations of respiratory allergens mainly involve 1-3 types,and mugwort,cat hair,and common ragweed are the most common aller-gens combined with dust mite.Therefore,prevention and control of allergic rhinitis should focus on the characteristics of dust mite allergy in this region.

Objective:To compare the clinical effectiveness between arthroscopic hollow screws combined with a suture anchor, hollow screws and proximal humerus internal locking system (PHILOS) in the treatment of split-type fractures of humeral greater tuberosity.Methods:A retrospective study was conducted to analyze the 54 patients with split-type fracture of humeral greater tuberosity who had been admitted to Department of Joint Surgery, Hospital of Traditional Chinese Medicine, Affiliated to Southwest Medical University from May 2015 to August 2020. There were 17 males and 37 females with an age of (58.4±12.1) years. According to different treatment methods, they were divided into 3 groups. Group A of 18 cases was treated with arthroscopic hollow screws combined with a suture anchor, group B of 18 cases with hollow screws, and group C of 18 cases with PHILOS. The length of surgical incision, and range of shoulder motion, visual analogue scale (VAS), and American Shoulder and Elbow Surgeons (ASES) score at the last follow-up were recorded and compared between the 3 groups.Results:There was no statistically significant difference in the preoperative general information between the 3 groups, indicating the 3 groups were comparable ( P>0.05). The surgical incision in group A [(0.7±0.1) cm] was the shortest, followed by (5.0±1.4) cm in group B, and (12.8±2.1) cm in group C, showing statistically significant differences in pairwise comparison ( P<0.05). In the 3 groups at the last follow-up, respectively, the shoulder forward flexion was 159.7°±13.4°, 154.9°±16.2°, and 160.5°±12.9°, and the shoulder abduction 149.6°±11.3°, 142.4°±12.0°, and 145.1°±10.4°, showing no statistically significant difference among the 3 groups ( P>0.05); the external rotation was 41.1°±8.1°, 38.1°±7.8° and 43.7°±6.2°, showing a statistically significant difference between groups B and C ( P<0.05); the dorsal extension was T 12 (L 5 to T 6), T 12 (L 5 to T 7), and T 12 (L 3 to T 6), showing no statistically significant difference among the 3 groups ( P>0.05). There was no statistically significant difference among the 3 groups in the VAS score or ASES score at the last follow-up ( P>0.05). Respectively, there were 2, 6, and 4 patients in groups A, B and C who developed complications, showing statistically significant differences between the 3 groups ( P<0.05). Conclusions:In the treatment of split fractures of humeral greater tuberosity, arthroscopic hollow screws combined with a suture anchor, hollow screws and PHILOS can all relieve pain and restore joint function of the shoulder. However, arthroscopic hollow screws combined with a suture anchor are the most recommendable due to their advantages in minimally invasiveness and reduction in complications.

Objective: To evaluate the effect of Triangle hierarchical management among community patients with hypertension, so as to provide insights into the improvements of standardized hypertension management. Methods: Patients with newly diagnosed hypertension from 2 community health service centers in Qiantang District of Hangzhou City by the end of 2020 were randomly assigned to the conventional group and the Triangle group. Patients in the conventional group were given health management services according to the requirements of basic public health service standard for one year, while patients in the Triangle group were given Triangle hierarchical management. The blood pressure, self-management behaviors, treatment compliance, smoking, alcohol consumption and exercise were collected using the self-management behavior scale, treatment compliance scale and self-designed questionnaires, and were compared before and after intervention with analysis of covariance and generalized estimation equations. Results: Totally 200 patients with hypertension were recruited, including 100 patients in the conventional group and 100 patients in the Triangle group. There were no significant differences between the two groups before implementation of interventions in terms of gender, age, educational level or occupation (P>0.05). The reduction in blood pressure, increase in the score of treatment, diet, exercise and living habitat management and the total score of self-management behaviors, increase in the score of adherence to medication regimens, daily living management behaviors, smoking and alcohol consumption preference and the total score of treatment compliance, and increase in the number of patients with normal standard of quitting smoking, quitting alcohol consumption, exercise and blood pressure were significantly higher in the Triangle group than in the conventional group after intervention (P<0.05). Conclusions Triangle hierarchical management may increase the treatment compliance, improve the self-management behavior and facilitate hypertension control among hypertensive patients, which may be popularized for health management among community patients with hypertension.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals ; Cell Differentiation ; Flavanones ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism* ; Oligodendroglia/metabolism* ; Rats ; Remyelination ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

Objective:To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO 2/FiO 2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO 2/FiO 2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO 2, SpO 2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. Results:Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ β values were -15.827, 1.202, 95% confidence interval (95% CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. Conclusion:Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

To construct an intelligent appointment register platform for clinical examination in large-scale hospitals can improve the utilization efficiency of medical resources and shorten the waiting period of patients for examination. In this study, a knowledge base of medical examination information was built through the investigation of general hospital, and all examination systems and items were integrated into the appointment register platform, so that all examinations were appointed based on the principle of completing all tests in the shortest time, thus building a unified intelligent appointment register platform for the hospital. From that, the average appointment register procedure of examinations has been shorten after launching the intelligent platform, labor costs of appointment register center and inpatient legwork have been saved, all examinations of inpatients can be finished in 48 hours, and patient satisfaction has been improved obviously.

Objective:To investigate the changes in gut microbiota diversity with age in elderly people using high-throughput sequencing.Methods:Ninety healthy volunteers were recruited. People who were <60 years old (middle-aged group) were set up as a baseline control group (Age A group), while those aged ≥60 years old were further divided into four groups (60-<70: Age B group, 70-<80: Age C group, 80-<90: Age D group, ≥90: Age E group). Fecal samples were collected to extract DNA. The second-generation sequencing technology was used to amplify and sequence the V3-V4 hypervariable region of 16S rDNA. Bioinformatics analysis was performed to compare the differences in gut microbiota and functional genes among groups.Results:At the phylum level, gut microbiota were composed mainly of Firmicute, Bacteroidetes, Proteobacteria and Actinobacteria in different groups. The proportion of Firmicute was the highest, accounting for over 60%, followed by that of Bacteroidetes. At the genus level, the abundance of Faecalibacterium genus decreased with age. The α diversity analysis showed that the gut microbiota in the elderly of different ages had higher abundance and uniformity, and there was no significant difference among groups. However, the β diversity analysis showed that in community structure there was difference between Age A and Age B groups, and similarity between Age B and Age C groups. Conclusions:The community structure of gut microbiota changed significantly between young and middle-aged people and the elderly over 60 years old. It tended to be relatively stable in people of 60-80 years old, but changed again when they were over 80 years old. Chronic inflammatory diseases, metabolic diseases and tumors in the elderly might be associated with the decrease in Faecalibacterium.

Objective:To explore the relationship between semi-quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and long-term prognosis of locally advanced nasopharyngeal carcinoma, and to find prognostic indicators from non-invasive images of locally advanced nasopharyngeal carcinoma.Methods:Data were collected from January 2011 to January 2012 via a prospective clinical trial with locally advanced nasopharyngeal carcinoma. Clinical information was from 71 patients who completed the treatment plan with long-term follow-ups and UICC 2010 stage Ⅲ, Ⅳ A, Ⅳ B. The patients received three cycles of Taxotere-Platinol-Fluorouracil (TPF) regimen chrono-chemotherapy, followed by two cycles of concurrent paclitaxel chemotherapy with intensity-modulated radiotherapy (IMRT). DCE-MRI examination was performed before induction chemotherapy to obtain DCE-MRI related semi-quantitative parameters. Correlation analysis was conducted between DCE-MRI related semi-quantitative parameters and short-term efficacy of nasopharyngeal lesions after concurrent radiotherapy and chemotherapy. Results:Of all 77 patients, 71 completed treatment and were followed up from 9 to 86 months, with a median follow-up of 77 months, with 80.2% and 67.6% in 3- and 5-year OS, 73.2% and 60.5% in 3- and 5-year PFS, respectively. Evaluation of short-term efficacy of nasopharyngeal lesions after concurrent chemoradiotherapy: the difference in tissue arrival time of contrast agent between complete response (CR) group and partial response (PR) group was statistically significant ( t=0.537, P<0.05). Univariate survival analysis found that OS ( χ2=3.982, P<0.05) and PFS ( χ2=4.019, P<0.05) in the group with short contrast arrival time were significantly higher than those in the group with long contrast arrival time. OS ( χ2=7.593, P<0.05) and PFS ( χ2=5.624, P<0.05) of patients aged over 45 years were significantly lower than those aged less than 45 years. Cox multivariate regression model showed that advanced clinical stage (stage Ⅳ A, Ⅳ B) ( P=0.048) and age≥45 years ( P=0.031) were independent prognostic factors of OS in patients with nasopharyngeal carcinoma. Long arrival time of contrast agent ( P=0.018), age≥45 years ( P=0.004), advanced N(2-3) stage ( P=0.032) and enhancement peak<3 000 ( P=0.005) were independent prognostic factors of PFS in patients with nasopharyngeal carcinoma. Conclusions:The arrival time of the contrast agent in DCE-MRI may be a reliable prognostic factor for locally advanced nasopharyngeal carcinoma.