Objective:To investigate the efficacy of Silybinin meglumine on hepatic fibrosis rats and possible mecha -nisms.Methods:The liver fibrosis rats were randomly divided into 4 groups,the model group,Silybinin meglumine 120 mg/kg group, Silybinin meglumine dose group 60 mg/kg and Silybinin meglumine low dose group 30 mg/kg,and the control group.All groups had been treated for 4 groups.Results:No deaths rat.Compared with the control group ,the reduced body weight ,less dynamic,dark hair, decreased liver and spleen indexes ,increased ALT,AST,TBIL,TG,TC and LDLC,and the decreased ALB, and the increased LXRαand SREBP1c had been observed in the model group (P<0.05).Compared with the model group ,better activity and body weight ,the in-creased liver and spleen indexs decreased ALT ,AST,TBIL,TG,TC and LDLC,and the increased ALB , and the decreased LXRαand SREBP1c had been observed in the Silybinin meglumine groups (P<0.05),in a way of dose-depended.Conclusion: The Silibinin meglumine can treat liver fibrosis ,by improving liver function,lowing lipid and decreaseing LXRαand SREBP1c expression in liver tis-sue.But the mechanism of two proteins reduced remains for further investigation .

han that in the control one (t=3.94, P<0.01).Conclusion Social skills training can effectively improve subjective satisfactions of the long-terra hospitalized patients with chronic schizophrenia.

The body mass index (BMI)is one of the important indexes to evaluate the nutrition / health status.BMI is weight in kilograms divided by height in per square meter (unit of kg/m2).BMI is changing with age.However,there are no BMI guidelines for the elderly.It is really necessary to set up a proper BMI range for the elderly.This research analyzed the relationship of BMI with all-cause mortality,cardiovascular mortality and body composition change in the elderly.The result showed that an appropriate higher BMI could help to decrease the all-cause mortality and cardiovascular mortality in the elderly and could also increase bone density and lean body mass,which could prevent the geriatric fracture and sarcopenia.Furthermore,underweight-related mortality was much higher than overweight-related mortality.

Objective To retrieve,evaluate and integrate evidence related to prevention and management of lifestyle-related dry eye patients.Methods The clinical decisions,recommended practices,evidence summaries,technical reports,guidelines,expert consensuses and systematic evaluations on the prevention and management of lifestyle-related dry eye patients in domestic and foreign databases were retrieved by the computer.The evidence was extracted and summarized according to the subject after the independent literature quality evaluation by 2 researchers.The literature retrieval time limit was from the establishment of the databases to September 2022.Results According to the inclusion criteria,13 pieces of the literature were screened,including 1 guideline,5 systematic reviews,3 expert consensuses,2 technical reports and 2 evidence summaries.Through literature reading,evidence extraction and classification,a total of 25 pieces of evidence were summarized,including assessment,symptom identification,identification of risk factors,artificial tear management,eye care,diet management,health guidance,follow-up education.Conclusion This study summarized the best evidence of prevention and management of lifestyle-related dry eye patients,so as to provide references for nurses to carry out clinical practice.In the process of evidence transformation,the actual situation should be combined to improve the quality of nursing.

Objective:To investigate the epidemiological characteristics and transmission chain of COVID-19 in two families, and to provide scientific evidence for effective prevention and control measures.Methods:Field epidemiological investigation was conducted for the COVID-19 cases occurred in two families and the close contacts in a county of Baotou city in Inner Mongolia Autonomous Region. Descriptive statistical analysis on epidemiological data was conducted.Results:The infection source of the COVID-19 cases in the two families was a man who had living history in Wuhan. After his return, his parents were infected by him. A few days later, the members of a neighbor family were found to be infected, and relatives of this family were also infected after dining together repeatedly. Finally, ten confirmed cases and three suspected cases of COVID-19 were detected in the two families.Conclusions:Human-to-human transmission of COVID-19 can occur not only in a family but also in neighborhoods. The cases in two families had close relationship, indicating the necessity to strengthen the health education about COVID-19 prevention and control and the management of groups at high risk to reduce the incidence of COVID-19 in families and neighborhoods.

In order to study the molecular mechanism and physiological significance of the interaction between PGRN and Rev-erbβ, the PGRN gene in HEK293 (Rev-erbβ-/-) marked as C3-6 cell lines was knocked out by CRISPR/Cas9 system to generate the Rev-erbβ and PGRN double genes knockout HEK293 cell lines. First, four sgRNAs were designed for PGRN gene, and PGRN sgRNA2 and sgRNA3 with the higher activity were used to construct the Lentiviral vector, pLenti/CMV-Loxp-Cas9-sgRNA2-U6-sgRNA3-U6-Loxp-EF1α-Puro. Then, the lentivirus vector carrying Cas9 and double PGRN sgRNA were used to infect HEK293 C3-6 cells. Through drug screening, cloning and sequencing, we obtained the monoclonal HEK293 (Rev-erbβ-/-; PGRN-/-) marked as C3-6/23 cell lines. Using qRT-PCR and Western blotting, we detected PGRN mRNA and protein expression in C3-6/23 cell lines. Finally, genetic complementation was used to study the effect of PGRN-mediated Rev-erbβ on the regulation of the target gene promoter transcriptional activity in the C3-6/23 cell lines. In HEK293 C3-6/23 cell lines, the two DNA chains of PGRN gene were both deletion mutagenesis, and the expression mRNA and protein of PGRN did not reach the detection level. At the same time, the interaction between PGRN and Rev-erbβ enhanced the regulation of Rev-erbβ on the transcription of target gene promoter in the cell lines. Using CRISPR/Cas9 system, we successfully constructed the double knockout HEK293 (Rev-erbβ-/-; PGRN-/-) monoclonal cell lines. The study found that PGRN could affect Rev-erbβ on the regulation of target gene promoter transcription in the C3-6/23 cell lines; however, the mechanism of PGRN involvement in mediating Rev-erbβ in transcriptional regulation remains to be further studied.

Evidence-based medicine (EBM) is a science that uses the best available research data to make decisions, and the core is that clinical decision-making is supported by the best research evidence. Incorporating EBM into traditional standardized residency training in hematology can foster residents' professional theoretical knowledge and clinical skills, improve the quality of standardized training, and provide ideas and methods for standardized training of hematology residents, which is worthy of further research and exploration.

Objective:To observe the efficacy and safety of sirolimus combined with calcineurin inhibitor (CNI) in the treatment of glucocorticoid resistant/dependent extensive chronic graft-versus-host disease (cGVHD) .Methods:A total of 27 patients with steroid-resistant/steroid-dependent extensive cGVHD from November 2015 to January 2019 were enrolled and given sirolimus capsules combined with cyclosporine or tacrolimus to observe the clinical efficacy and adverse events.Results:The median duration of medication was 14.2 months and the mean duration was 16.7 months. The median follow-up time was 20.1 months (12.9-46.1 months) . Following the 6-month follow-up, 3 cases achieved complete response (CR) and 12 cases partial response (PR) . The overall response rate (ORR) was 55.6% ; for progression-free survival (PFS) , PFS-6 reached 88.9% (24/27) , and for overall survival (OS) , OS-6 was 100% . At the 1-year follow-up, there were 5 cases of CR and 11 cases of PR, ORR was 59.3% , PFS-12 reached 62.9% (17/27) , and OS-12 was 100% . The subgroup analysis found that the program was more effective for cGVHD in male donors and the target organ analysis had an advantage in the treatment of oral cavity, skin, and liver rejection. Adverse events were observed: hyperlipidemia 11.1% , oral ulcer 7.4% , fungal infection 11.1% , liver injury 3.7% , renal insufficiency 0, and no new CMV and EB viremia.Conclusion:Sirolimus combined with calcineurin inhibitors is effective in treating steroid-resistant/steroid-dependent extensive cGVHD, especially because adverse reactions (renal toxicity, CMV, EBV infection) are low in number, which is suitable for long-term treatment of cGVHD.

OBJECTIVETo study the blocking effect of CXCR4 inhibitor AMD3100 on the adhesion of leukemia cells to osteoblast niche, and the reversal of multidrug resistance in leukemia cells.

METHODSMesenchymal stem cells (MSCs) from leukemia patients were planted on the bio-derived bone scaffolds and then induced into osteoblasts to establish the bio-osteoblast niche. The levels of SDF-1were tested with ELISA. The leukemia cell line MV4-11 cells with FLT3-ITD mutation were inoculated into the bio-osteoblast niche to build a three-dimensional co- culture system. The expression level of CXCR4, adhesion and apoptosis rates of leukemia cells were observed by flow cytometry after incubation with AMD3100 and Ara-C for 24 h and 48 h.

RESULTS(1)The supernatant levels of SDF-1 in cultured osteoblast were (304 ± 18), (410 ± 28) and (396 ± 16) pg/ml on 7 th, 14 th and 21 th day, respectively. It reached the highest on 14 th day. The expression level of CXCR4 in cultured MV4-11 cells was (72 ± 16)%. (2)Adhesion rate of MV4-11 cells to osteoblast niche was (40.1 ± 8.1)% after AMD3100 treatment for 24 h, while that of control group was (65.6 ± 12.1)% (P<0.05). (3)The apoptosis rate of MV4-11 cells incubated with AMD3100 for 24 h was (5.6 ± 0.8)%, while that of control group was (2.5 ± 0.5)%. The apoptosis rates of AMD3100-induced MV4-11 cells were (10.0 ± 2.4)%, (17.8 ± 2.3)% and (25.1 ± 2.4)% after treatment with Ara-C at 0.02, 0.20, 2.00 mg/ml respectively and they were (6.7 ± 1.0)%, (10.3 ± 1.5)%, (16.2 ± 3.1)% respectively in AMD3100-noninduced control group, the difference was significant (P<0.05).

CONCLUSIONAMD3100 can block the interaction between osteoblasts niches and leukemia cells, and play an important role in the reversal of multidrug resistance in leukemia cells.

Apoptosis ; Cell Adhesion ; Cell Line, Tumor ; Chemokine CXCL12 ; Coculture Techniques ; Cytarabine ; Drug Resistance ; Flow Cytometry ; Heterocyclic Compounds ; Humans ; Leukemia ; Mesenchymal Stromal Cells ; Osteoblasts ; Receptors, CXCR4 ; Signal Transduction