BACKGROUND:Human mesenchymal stem cells derived from Wharton's jelly(WJCs)display the characteristics of MSCs as defined by the International Society for Cellular Therapy.They can be differentiated into bone,cartilage,adipose,muscle,and neural cells.They can also support the expansion of other stem cells,be weli-tolerated by the immune system,and have the ability to home to tumors.OBJECTIVE:To investigate biological changes of WJCs and brain tumor stem cells(BTSCs)co-cultured in vitro.METHODS:WJCs cultured by situ cultivation and BTSCs used enzyme digestion way respectively,and gathering the 3rd passage of WJCs though subculturing as well as BTSCs.Two kinds of cells co-cultured in 24-well plates in serum-free medium (SFM)without any growth factor.3 and 7 days after co-cultured respectively,CD133 expression of suspension cells in the 24-well plates were identified by flow cytometry,and immunofluorescence was performed for Nestin and glial fibrillary acidic protein (GFAP)expression of adherent cells.Co-culture supernatant(CCS)re-suspended 3~(rd) passage of BTSCs and cultured into 96-well plates at day 3,which were used to determine the difference in cell growth curve in both groups using a microplate reader.RESULTS AND CONCLUSION:With the cocultivation days increasing,the phenomenon that tumor sphere cells began to be decomposed,adherent and differentiated observed by an inverted microscope.BTSCs in the co-cultured group expressed GFAP and Nestin when adherent and differentiated.The higher degree of malignant brain tumor tissue used in culturing BTSCs was,the higher expression of CD133 in BTSCs was.CD 133~+ in BTSCs declined when co-cultured with WJCs.Growth curve of brain tumor stem cells cultured in CCS compared with in SFM at day 3,which indicates that the proliferation of BTSCs inhibited obviously.Results indicated that CD 133~+ expression and proliferative capacity of BTSCs went down and BTSCs underwent differentiation during the co-culture in vitro.

BACKGROUND:Bone marrow mesenchymal stem cells have low immunogenicity and immunomodulatory effect,but there are seldom reports concerning the immunomodulatory effect of Wharton's jelly-derived mesenchymal stem cells of human umbilical cord and its mechanims.OBJECTIVE:To investigate the immunomodulatory effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells of human umbilical cord on varient peripheral blood T lymphocytes.METHODS:Mesenchymal stem cells were isolateded from Wharton's jelly of human umbilical cord by tissue culture.T lymphocytes from human peripheral blood were stimulated by phytohemagglutinin and co-cultured with umbilical cord Wharton's jelly-derived mesenchymal stem cells and umbilical cord Wharton's jelly-derived mesenchymal stem cells supernatant respectively to measure A value following 72 hours of coculture using multifunctional microplate reader.Expression of cytokines including transforming growth factor-beta 1(TGF-β1)and interferon-y(IFN-γ)was evaluated by enzyme-labeled immunosorbent assay.RESULTS AND CONCLUSION:Wharton's jelly-derived mesenchymal stem cells could inhibite the proliferation of T lymphocytes induced by phytohemagglutinin.The proliferation inhibition rate was 56%(P＜0.01).Wharton's jelly-derived mesenchymal stem cells supernatant also had inhibitory effects on proliferation of T lymphocytes induced by phytohemagglutinin,in a dose-dependent fashion.The proliferation inhibition rates were 8.3% and 27% respectively in the 50% Wharton's jelly-derived mesenchymal stem cells supernatant and 100% Wharton's jelly-derived mesenchymal stem cells supematant groups(P＜0.05).Wharton's jelly-derived mesenchymal stem cells significantly decreased γ-interferon secrted from T-lymphocytes(P＜0.05).The secretion of TGF-β1 was lower in the coculture of Wharton's jelly-derived mesenchymal stem cells and T lymphocytes group than Wharton's jelly-derived mesenchymal stem cells alone group(P＜0.05).These indicated that Wharton's jelly-derived mesenchymal stem cells and Wharton's jelly-derived mesenchymal stem cells supernatant have inhibitory effects on proliferation of T lymphocytes induced by phytohemagglutinin.The mechanims may be associated with cell contant and inhibition of v-interferon secrted from T-lymphocytes.

Objective:To explore indications for replantation of proximal proper digital artery and establishing extrinsic arterial perfusion pressure in the treatment of special type of severed digits with avulsion over 12.0 hours of warm ischemia, and to analyse the factors that affected the survival rate of the replanted digits.Methods:From September 2014 to January 2022, 8 patients with severed digits and prolonged warm ischemia were treated by transposition of adjacent digital artery together with the technique of extrinsic arterial perfusion pressure in the Department of Wrist and Hand Surgery, the Orthopaedic Hospital in Sichuan Province. During the operation, the defected proximal proper digital artery was reconstructed and repaired with vein graft, one side of the digital artery was repaired with an inverted "Y" vein graft, and one side of "Y" vein was bridged and anastomosed to repair the original digital artery. On the other side, the adjacent proximal proper digital arteries were transpositioned and anastomosed to gain an extrinsic arterial perfusion pressure, which increased the distal haemodynamic and reconstituted the blood supply. Of the 8 patients (9 severed digits) : 1 had severed index and middle fingers, 2 had severed index fingers, 4 had severed thumbs and 1 had severed little finger. All the patients were males, aged 16-63 years old, at 37.6 years old in average. Warm ischemia time of the severed digits were 12.3-20.6 hours, with 17.4 hours in average. The survival rate of replanted digits was observed after surgery. Postoperative follow-ups were conducted through telephone or WeChat reviews.Results:Follow-up time was 6-26 months, at 8.3 months in average. Retrospective analysis was performed. Vascular compromises occurred in 3 patients 4 digits (arterial insufficiency in 1 digit, venous congestion in 3 digits), skin necrosis occurred in 1 patient (1 digit) and digit necrosis in 1 patient (1 digit). Overall, 8 of the 9 replanted digits survived. According to the Replantation Function Evaluation Standard of Hand Surgery Association of Chinese Medical Association, the digit function after replantation was evaluated at excellent in 6 digits, good in 1 digit and poor in 1 digit.Conclusion:For a severed digit with an ischemia time over 12.0 hours, the survival rate can be improved by transposition of an adjacent digital artery to provided extrinsic arterial perfusion pressure.

Objective To investigate the prevalence and influencing factors associated with frailty among institutional older adults and to provide evidence for intervention study.Methods A total of 237 older adults living in four welfare homes from Chengdu in Sichuan Province were recruited by convenience sampling.A cross-sectional survey was conducted,and frailty was assessed by the frailty phenotype;general information was collected by selfmade general information questionnaire;functional capacity was assessed by Barthel questionnaire;depressive status was assessed by GDS-15;cognitive function was assessed by clock drawing test and nutritional status was assessed by short form mini nutritional scale questionnaire (MNA-SF).Results The reported rate of frailty was 55.69％ among institutional older adults,and 44.31％ reported no frailty;grip weakness (207,87.3％),slow walking speed (172,72.6％) and low physical activity(131,55.3％) were the main frailty problems.Univariate analysis showed that the elderly'frailty conditions were different in the pre-retirement occupations,smoking,alcohol consumption,physical exercise,chronic diseases,medication,acute events (last year),self-reported health,using assisted walking devices,ability of daily life,depression,cognitive ability and nutritional status,and the differences were statistically significant(P＜0.05).Conclusion The status of frailty is not optimistic among institutional older adults and many factors are associated with frailty.Healthcare providers should pay more attention to the frailty issue and take timely intervention strategies to prevent or delay the frailty.

Purpose To explore the molecular features of diffuse large B-cell lymphoma(DLBCL)with high expression of MYC.Methods The clinical data of 45 cases of DLBCL were collected.Immunohistochemical EnVision method was used to classify the patients into the group with high expression of MYC and the group with low expression of MYC.All samples were subjected to DNA targeted sequencing and molecular typing was performed using the LymphGen online tool.Cellular origin was determined by using the Lymph2Cx method.The correlation be-tween MYC overexpression and clinicopathological parameters was analyzed by the x2 test and Fisher precise test.Survival curves were drawn and survival-related factors were analyzed u-sing Cox univariate and multivariate regression.ResultsCases were classified into DLBCL with high expression of MYC(n=17)and DLBCL with low expression of MYC(n=28).Com-pared to the group with low expression of MYC,the group with high expression of MYC had more PIM1,MYD88,CD79B,CD58 and PRDM1 mutations(76.5％vs 28.6％,70.6％vs 32.1％,58.8％vs28.6％,29.4％vs3.6％,29.4％vs 3.6％,P＜0.05),MCD were more frequently found(58.8％vs 10.7％,P=0.001),GCB were rarely found(17.6％vs 50.0％,P=0.030).Overall survival was significantly shorter in DLBCL with high expression of MYC(P＜0.05).Cox multi-factorial analysis showed that age was an independent prognostic factor for DLBCL(P＜0.05).Conclusion Patients with high expression of MYC were frequently characterized as MCD and ABC,and PIM1,MYD88,CD79B,CD58 and PRDM1 muta-tions were common.Patients with high expression of MYC had a poorer prognosis.

Objective:To explore the risk factors for atrial fibrillation(AF)in elderly Chinese patients with severe valvular heart disease(VHD).Methods:This was a cross-sectional study and consecutively enrolled 978 elderly patients with severe VHD diagnosed in 18 Class A tertiary hospitals across the country from September 2021 to March 2022, including 322(32.9%)patients with concurrent AF.Clinical and echocardiographic data were collected to analyze the risk factors for AF.Results:Among VHD patients, compared with the non-AF group, the AF group was older, had a higher female ratio, higher diastolic blood pressure, higher proportions with cerebrovascular disease and chronic kidney disease, lower serum low density lipoprotein cholesterol and higher serum creatinine, amino-terminal A-type natriuretion peptide and glycosylated hemoglobin.As for echocardiographic parameters, the left atrial diameter was larger, the left ventricular end-diastolic diameter, interventricular septum thickness, and left ventricular posterior wall thickness were smaller in the AF group than in the non-AF group.All of the differences were statistically significant(all P<0.05). The results of multivariate Logistic regression analysis showed that the left atrial anteroposterior diameter increased( OR=1.166, P<0.01), the left ventricular end-diastolic diameter decreased( OR=0.929, P<0.01), and advanced age( OR=1.051, P<0.05)was an independent risk factor for elderly VHD patients with concurrent AF. Conclusions:In elderly patients with severe VHD, advanced age, an increased left atrial anteroposterior diameter, and a decreased left ventricular end-diastolic diameter were independently associated with AF.Therefore, evaluation of cardiac structure and regular follow-up should be performed in elderly patients with severe VHD for early intervention to reduce the incidence of AF.

Early phase trials refer to the early exploratory stage of transferring drug development into clinical trials. With China's strong encouragement for innovative drug research and development and enterprises vigorous investment, a large number of innovative drugs have entered early clinical trials. Early phase trials are generally based on innovative diagnosis and treatment mechanisms, pharmaceutical technology and drug delivery methods. Their research design are complex and diverse, and the new technology such as computer simulation are also widely used in the early phase trial process. These aspects are major challenges for the scientific and ethical review of early phase trials. Based on the characteristics of early phase trials, this article analyzes the ethical issues in early clinical trials such as risk uncertainty, therapeutic misunderstanding, subject compensation, breakthrough treatment, etc., and puts forward ethical countermeasures and suggestions.

OBJECTIVETo compare the clinical efficacy differences between acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method and traditional acupoint plaster therapy for senile osteoporosis (SOP).

METHODSWith randomized controlled blind design, 76 SOP patients with deficiency of liver and kidney syndrome were randomly divided into an observation group and a control group, 38 cases in each one. Based on oral administration of caltrate D, the patients in the observation group were treated with acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method at Yingu (KI 10), Taixi (KI 3), Dazhong (KI 4), Fuliu (KI 7) and Zhiyin (BL 67), while the patients in the control group were treated with traditional acupoint plaster therapy. Each plaster therapy lasted for 6 h, once a day; there was an interval of 2 d after consecutive 5-day treatment; 4 weeks were taken as one course, and totally 2 courses were given. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the pain and dysfunction before intervention, after 4 weeks and 8 weeks intervention. Osteoporosis symptom rating sale and quality of life questionnaire of the European foundation for Osteoporosis (QUALEFFO-41) were adopted to evaluate the TCM syndrome and quality of life before and after 8-week intervention.

RESULTSAll the outcomes were significantly improved after treatment in the two groups (<0.01,<0.05); after 4 weeks and 8 weeks of treatment, the VAS and ODI in the observation group were lower than those in the control group (all<0.05). Repeated ANOVA indicated the VAS and ODI were significant in group effect, time effect and interaction effect (all<0.01). Further comparison showed that VAS and ODI at later time points were lower than those in the early time points (all<0.01). After the treatment, the scores of TCM syndrome and QUALEFFO-41 in the observation group were lower than those in the control group (all<0.05). The effective rate was 85.7% (30/35) in the observation group, which was superior to the effective rate in the control group[74.3%(26/35),<0.05].

CONCLUSIONSThe acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method is superior to traditional acupoint plaster therapy in improving pain, dysfunction, TCM syndrome and quality of life in SOP patients; in addition, its clinical efficacy is significant.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Liddle syndrome and Gordon syndrome are two rare single-gene inherited hypertension diseases. In patients≤40 years, the prevalence of Liddle syndrome is about 1% and Gordon syndrome is uncertain all over the word, for which is often misdiagnosed and mistreated. The therapies of those diseases are targeted at gene mutation sites, as well as combined with modified lifestyle, and can achieve satisfactory diseases control. This paper reports a patient who is diagnosed with Liddle syndrome and Gordon syndrome at the same time. We aimed to consolidate and improve the diagnosis and accurate treatment of those two diseases by sharing, studying and discussing together with clinical doctors.