BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) have been widely accepted by medical investigators due to their advantages including easy obtaining, minimal invasion, with infinite proliferation and multi-differential potential, and without immunological rejection in the autologous transplantation. OBJECTIVE: The goal of this study is to isolate and purify rat bone marrow MSCs in vitro, so as to observe the effects of different concentrations of serum containing kidney-tonifying and blood-activating Chinese herbs on the in vitro proliferation of rat bone marrow MSCs.DESIGN: A randomized controlled animal experiment.SETTING: Hip Center, First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine.MATERIALS: Forty healthy male SD rats of SPF grade, weighing 170 to 180 g, were provided by the Laboratory Animal Center, Guangzhou University of Traditional Chinese Medicine. The protocol was performed in accordance with ethics guidelines for the use and care of animals. The involved rats were divided into 4 groups by random digit table with 10 rats in each: normal control group, high-, middle-, and low-concentration groups. METHODS: This study was performed at the Laboratory Animal Center, Guangzhou University of Traditional Chinese Medicine between January and March 2005. Rat bone marrow MSCs were isolated and purified by Percoll density gradient centrifugation, and cultured in vitro to establish rat bone marrow MSCs culture system. Rats in the high-, middle-, and low-concentration groups were intragastrically administrated with 4.4, 2.2 and 1.1 g/kg serum containing kidney-tonifying and blood-activating Chinese herbs, which equaled to 20, 10 and 5 times of adult dosage, respectively. Rats in the normal control group were intragastrically administrated with purified water for 1 week. One hour after the last administration, 6 mL blood was taken from abdominal aorta of each rat under the aseptic condition. Then, it was centrifuged at 2 000 r/min for 15 minutes, and meanwhile serum was collected. 10% rat serum containing kidney-tonifying and blood-activating Chinese herbs was added to the medium in the high-, middle-, and low-concentration groups, while 10% fetal bovine serum was added in the normal control group. MAIN OUTCOME MEASURES: ① MSCs growth status; ② MSCs morphology was observed by HE staining and Giemsa's staining; ③ MSCs antigen expression was detected by an immunocytochemical method; ④ Effects of different concentrations of serum containing kidney-tonifying and blood-activating Chinese herbs on MSCs growth.RESULTS: ①The primarily cultured bone marrow MSCs began to adhere to the wall 24 hours later and 80% of them reached the confluence 7 days later. ② MSCs took appearance in long shuttle shape or polygon. These cells were little. Nuclei were located in the middle part of cells or a little deviation. The ratio of nucleus to cytoplasm was a little high. ③CD44 expression was found in the cytoplasm of mononuclear cells, and colored blue. Partial MSCs expressed c-Kit. Their cytomorphology and phenotypic expression have the characteristics of MSCs. ④Three days after serum containing kidney-tonifying and blood-activating Chinese herbal medicine being added to high-, middle-, and low-concentration groups, the number of bone marrow MSCs was dose-dependently increased as compared with that in the normal control group. CONCLUSION: Serum containing kidney-tonifying and blood-activating Chinese herbs promotes the in vitro proliferation of bone marrow MSCs.

OBJECTIVETo identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB).

METHODSA total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014. All participants were Chinese Han residing in Shanghai and the surrounding areas. The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434). History of hepatitis B infection and HCC, as well as clinical data from serological, imaging and pathological examinations were collected for analysis.SPSS software, version 19.0, was used for all statistical comparisons.

RESULTSSingle factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex, age of 50 years or more, family history of HCC, alcohol consumption,fatty liver, detectable levels of hepatitis B virus (HBV) DNA, and history of HBV infection without effective antiviral treatment. Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005, odds ratio [OR] =1.766), history of alcohol consumption (P =0.002, Or = 2.570), family history of HCC (P =0.014, Or = 2.268), fatty liver (P =0.023, Or = 3.390), and history of HBV infection without effective antiviral treatment (P < 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014, Or = 2.537), family history of HCC (P =0.037,Or = 3.339) and fatty liver (P =0.018, Or = 11.646).

CONCLUSIONRisk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC, fatty liver, and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC, and fatty liver disease, were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.

Alcohol Drinking ; Antiviral Agents ; Carcinoma, Hepatocellular ; Case-Control Studies ; China ; Fatty Liver ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Male ; Odds Ratio ; Risk Factors

Objective:To compare the short-term clinical outcomes of robotic distal pancreatectomy(RDP) with laparoscopic distal pancreatectomy(LDP).Methods:PubMed, Embase, Cochrane library, Wanfang data, CNKI were searched systematically.Studies that compared short-term clinic outcomes between RDP and LDP groups were included. Observation indicators include: operation time, intraoperative blood transfusion rate, spleen preserving rate, spleen vessels preserving rate, conversion rate to open surgery, complication rate, severe complication rate, pancreatic fistula rate, severe pancreatic fistula rate, length of hospital stay, etc. The Meta-analysis was performed by using RevMan5.3.Results:Eleven non-randomized controlled trials with 791 patients meet the inclusion criteria.This Meta-analysis shows: compared with LDP group, RDP group was associated with higher spleen preserving rate ( OR=2.32, 95% CI: 1.07-5.04, P=0.03), higher splenic vessels preserving rate ( OR=3.07, 95% CI: 1.10-8.57, P=0.03), lower conversion rate to open surgery ( OR=0.58, 95% CI: 0.35-0.97, P=0.04), shorter hospital stay ( MD=-2.42, 95% CI: -4.30 --0.55, P=0.01), longer operative time ( MD=27.11, 95% CI: 9.06-45.16, P<0.01). There was no significant difference in overall complications, severe complications, pancreatic fistula, severe pancreatic fistula, and transfusion rate between the two groups. Conclusions:RDP showed a slight advantage in short-term outcomes, and it is worthy of applying in large medical center. Further studies on the long-term outcomes of these surgical techniques are required.

Gallbladder cancer constitutes the most prevalent malignant tumor of the biliary tract. It exhibits clinical characteristics such as challenging diagnosis in early stages, aggressive invasiveness, and poor prognosis. Studies have discovered that the occurrence, development, and metastasis of malignant tumors are closely associated with the inflammatory response, and the level of systemic inflammation within the body can be reflected by peripheral blood inflammatory indicators. This review delineates the research progress on the correlation between peripheral blood inflammatory markers and the prognosis of gallbladder cancer, with the intention of providing references for the diagnosis, treatment, and prognosis evaluation of gallbladder cancer.

OBJECTIVETo observe the synergistic effects of paclitaxel and gemcitabine on prostate cancer cell line PC-3 in vitro.

METHODSCell morphology, MTU, flow cytometer and immunocytochemical method were used to observe the effects of 10(-6), 10(-7), 10(-8) mol/L paclitaxel and 10(-7), 10(-8), 10(-9) mol/L gemcitabine on prostate cancer cell line PC-3 by single or synergistic administration for 48 hours in vitro.

RESULTSGemcitabine above 10(-8) mol/L enhanced the growth suppression [suppression ratio > or = (50.8 +/- 4.2)%, P < 0.05] and apoptosis [apoptosis ratio > or = (22.9 +/- 2.3)%, P < 0.05] and down-regulation of the expression of cyclin D1 [expression ratio < or = (9.6 +/- 1.6)%, P < 0.01] induced by paclitaxel above 10(-7) mol/L in PC-3 cells. Gemcitabine changed the ratio of G2/M cell arrest induced by paclitaxel from (70.3 +/- 9.7)% to (38.2 +/- 4.2)%, and reversed the G2/M arrest partially (P < 0.01).

CONCLUSIONPaclitaxel and gemcitabine can enhance the growth suppression and apoptosis induced by paclitaxel in a synergistic way. They show great potential in the treatment of androgen-independent carcinoma of the prostate.

Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Synergism ; Flow Cytometry ; Humans ; Male ; Paclitaxel ; pharmacology ; Prostatic Neoplasms ; pathology

Objective To construct an intervention program for diabetic retinopathy(DR)patients undergoing surgery based on the theory of'Timing It Right'.Methods Guided by the theory of'Timing It Right',based on literature review and semi-structured interview,the first draft of the intervention program was formulated.From December 2022 to February 2023,15 medical and nursing experts in ophthalmology and endocrinology from 5 provinces(cities)in Zhejiang,Sichuan,Shanxi,Chongqing and Shanghai were interviewed by Delphi expert for 2 rounds to seek their advice and revision,and the final draft was formed.Results The effective recovery rate of 2 rounds of expert consultations was 93.75％and 100％.The authority coefficients were 0.87.The importance and feasibility of Kendall'W coordination coefficients were 0.325,0.138 and 0.193,0.141 in 2 rounds,respectively(P＜0.001).The finalized intervention program consisted of 6 months,which included 5 first-level items,18 second-level items and 43 third-level items.Conclusion The intervention program for DR patients undergoing surgery based on the theory of'Timing It Right'is reliable,scientific,feasible and practical,and it can meet the needs of such patients,providing a reference for improving their self-management ability,improving their negative emotions and delaying disease progression.

Objective To explore the good death status of terminally ill cancer patients from the nurses' perspective and identify associated factors. Methods A cross-sectional survey was conducted among the nurses in charge of the patients within 3 months after their death to evaluate the status quo of patients with end-stage cancer from the perspective of nurses, using anonymous questionnaire. Using convenient sampling method, 101 competent nurses from 209 patients with end-stage tumors who died in a hospital from October 2017 to January 2018 were selected. The nurses were investigated with nurses' general information questionnaire, patient information questionnaire and Good Death Inventory (GDI). Single factor analysis, Pearson correlation and multivariate linear regression analysis were used to analyze the influencing factors of good death in patients with end-stage cancer. Results The total score of GDI was (243.00±39.21). Among GDI, the three lowest scores were independence (7.43±4.25), physical and psychological comfort (8.17±4.82), and religious and spiritual comfort (8.53±4.72);while the three highest scores were being respected as an individual (18.32±2.76), good relationship with medical staff (18.23±2.59), and natural death (17.97±3.42). There were significant differences in patients' death status among different departments, medical payment methods, professional training experience of competent nurses and treatment methods within 3 months before death (t=17.351, 2.158, -2.679, -2.993;P＜0.05). Pearson correlation analysis showed that nurse working life was positively correlated with the total score of GDI (r=0.953, P＜0.01). Regression analysis showed that the factors influencing the good death of patients with end-stage cancer were the department of oncology medicine, the way of treatment and the professional training experience of nurses (P＜0.05). Conclusions The overall status of good death of terminally ill cancer patients is poor. To strengthen the palliative care training about the knowledge and skills helps to improve the nursing quality of end-of-life care and achieve the goal of good death.

Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.