Objective: To provide hospital managers the financial risk warning information, in order to avoid risk better. Methods:Use the analysis of corporate balance sheets as reference to compare and analyze 2 years ’ structural changing degree and structural rate of financial data project in hospital balance sheets and medical income schedule. Results: There are financial risks and operation risks existed in hospital economic operation. Conclusion: Balance sheet could be applied in the macro-control of capital structure to make correct decision for operation management; existing problem of management could be discovered from the micro-side of the medical income fees sheet, so as to improve the qualified management of the hospital.

Objective This study aims to investigate the mutation spectrum and frequency of GJB2 , mtDNA12SrRNA,and SLC26A4 genes in Hui people,Tibetan,Tu nationality,and Mongolian patients with non-syndromic hearing loss in Qinghai province.Methods Peripheral blood samples were obtained from a total of 211 minority patients with nonsyndromic hearing loss in Qinghai province to extract genomic DNA.Three genes of GJB2,mitochondrialDNA12SrRNA,and SLC26A4 were screened for mutations in our study cohort using SNPscan technology.Results Among these 211 patients,5 Tu patients and 1 Mongolian patient were found to carry the ho-moplasmic mtDNAA1555G mutation.The GJB2 mutations detection rates were 11.38%,4.55%,5.88%,and 10%in Hui people,Tibetan,Tu nationality,and Mongolian patients,respectively.No statistically significant differences in the GJB2 mutations detection rates were found among all four ethnicities (P>0.05).c.235delC was the most prevalent mutation in both Tu patients and Mongolian patients.The allele frequency was 2.94% and 5%,respec-tively.While for Hui patients,c.299 300delAT was the most prevalent mutation with the allele frequency of 4.47%.The mutations detection rates of SLC26A4 were 6.5%,4.55%and 2.94%in Hui people,Tibetan,and Tu nationality patients,respectively.No statistically significant differences in the SLC26A4 mutations detection rates were found among all three ethnicities (P>0.05).c.235delC was the most prevalent mutation in Hui patients,the allele frequency was 2.44%.While for Tibetan patients,c.1226G>A was the most prevalent mutation with allele frequency of 2.27%.Conclusion A total of 10.9% of deaf patients have inherited hearing impairment caused by GJB2,SLC26A4,and mtDNAA1555G mutations.The mutation spectrum of GJB2 and SLC26A4 genes has the eth-nic specificity in nonsyndromic hearing loss patients of minority ethnicities in Qinghai province.

Objective To explore the association between the genetic polymorphism of CYP3A4,CYP2D6 and response to methadone maintenance treatment(MMT)among heroin-dependent patients.Methods Patients undergoing MMT in 6 MMT clinics were randomly selected,information about general socia-demographic characteristics,drug abuse history,and MMT data of patients were collected,genotypes of peripheral blood CYP3A4 and CYP2D6 polymorphic loci were detected.Results A total of 820 patients were enrolled in the study,210 cases were with good response and 610 cases with poor response to MMT.Difference in age between different response groups was statistically significant(P<0.05).Distribution of genotype frequency and allele frequency of CYP3A4 rs2242480 and CYP2D6 rs16947 between good response and poor response groups was not significantly different(both P>0.05).Conclusion The association between CYP3A4 rs2242480,CYP2D6 rs16947 and response to MMT has not yet found in heroin-dependent patients.

Objective To determine which parameters of reverse remodeling of left ventricular could become the effective indexes in evaluating the short-term therapeutic effect of cardiac resynchronization therapy(CRT)in heart failure(HF)patients.Methods CRT was performed in 26 HF patients with dysfunctions of wall motion.Serial echocardiography was practiced at baseline,one and three months after CRT.The parameters including left atrial end-diastolic diameter(LADD),left ventrieular end-diastolic diameter(LVDD),end-diastolic volume (LVEDV),end-systolic volume(LVESV),ejection fraction(LVEF)were measured and compared before and after CRT therapy.Results At one and three months after CRT,respectively,CRT was associated with reduced LADD,LVDD,LVEDV,LVESV and improved LVEF and filling time compared with those at baseline.Moreover,all these parameters had better correlations with the activities of these patients.Conclusions LADD,LVDD,LVEDV,LVESV and LVEF could become the effective indexes in evaluating the short-term effect of CRT in HF patients.The reduced diameters and volumes of left atria and left ventricle are more sensitive parameters than the improved LVEF.

Objective To observe clinical curative effect of the FLAG regimen combined donor lymphocyte infusion after granulocyte colony stimulating factor(G‐CSF) mobilization(G‐DLI) ,for the acute myeloid leukemia (AML) of allogeneic Peripheral blood hematopoietic stem cell trans‐plantation (allo‐HSCT) after recurrence of hematology .Methods For the patients with recur‐rence after allo‐HSCT ,giving the FLAG regimen chemotherapy when the WBC dropped to the lowest point ,followed by giving G‐DLI that infusion peripheral blood stem cell from the original donors ,to observe curative effect and survival situation .And searched the literature review through the PubMed etc .Results Through FLAG regimen combined G‐DLI ,3 cases of relapse after transplan‐tation again obtained complete remission (CR) .Case 1 :disease‐free survival (DFS) was 13 month and overall survival(OS) was 23 months after G‐DLI .The patient has been the central recurrence and remission in bone marrow ,he was dead after 23 months due to multipleorgan function failure .He occurred Ⅱ acute GVHD in Skin and Ⅰ acute GVHD in liver after G‐DLI and obtained effective control ,not chronic GVHD .Case 2 :DFS and OS were 12 months and 13 months ,as bone marrow relapse again and giving up treat‐ment ,so died a month later .Respectively ,he has limitations chronic GVHD in skin after G‐DLI .Case 3:DFS was 16 months after G‐DLI since the disease‐free survival ,had limitations GVHD in skin that was control for given small dose of immunosuppressive drugs .Conclusion Joint FLAG scheme and G‐DLI may be one of the effective treatment of postoperative recurrence of allo‐HSCT .

Since the approval of gemtuzumab ozogamicin, an antibody–drug conjugate (ADC) targeting CD33 in 2000, 13 ADC drugs have been approved by the FDA. Although these drugs have clearly improved the survival of patients with various types of advanced cancers, their significant toxicity has compromised their therapeutic benefits. The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities, where the payload drug is a determining factor. Antibody and linker may also affect the degree of toxicity. Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency, but treatment-related adverse reactions also increase accordingly. This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies, including but not limited to optimizing linker molecules, upgrading antibody design, and changing drug administration strategies, to improve the overall safety profile of ADC drugs.

Objective:To cultivate human-derived prostate cancer (PCa) cells via conditional reprogramming cell (CRC) technology, and establish individualized cell bank for PCa research in vitro.Methods:We obtained three fresh PCa tissue samples from different patients between January 2019 and April 2019. Then each sample was divided into two parts. One was used for cancer nature confirmation by intraoperative biopsy. Another part was sent to the laboratory and digested into single primary cancer cells with 0.25% EDTA enzyme for CRC technology. The details were described as followed: 1. The primary PCa cells were co-cultured with 3T3-J2 cells irradiated by 30 Gy (feeder cells) in conditioned medium, and observed for the growth of cell clones, 2. The feeder cells were removed by 0.25% EDTA trypsin for 1 minute before primary PCa cells digested for passage. All primary PCa cells were validated by multiple experiments such as immunofluorescence, immunohistochemistry, immunoblotting and fluorescence in situ hybridization (FISH).Results:Total three cases of human-derived PCa cell lines were successfully established during 15days through CRC technology. All those primary PCa cells could be steadily and continuously passaged, which also expressed AR, CK5, CK18, P504s and PSA. FISH demonstrated that each cell line harbored≥1.6% TMPRSS2/ERG fusion and conformed to the features of PCa.Conclusion:CRC technology can be used for stable and continuous PCa cell culture in vitro.

Objective: To analyze the efficacy of HLA-haploidentical peripheral hematopoietic stem cell transplantation (haplo-PBSCT) following reduced intensity conditioning (RIC) regimen to treat the patients with hematological malignancies who were older than 50 years old. Methods: Eighteen patients with hematological malignancies over 50 years were enrolled, including 8 male and 10 female patients. The median age of all patients was 52 (range: 50–66) years. Of them, 8 patients had acute myeloid leukemia (AML) , 2 chronic myelocytic leukemia (CML) , 5 myelodysplastic syndrome (MDS) , 2 acute lymphoblastic leukemia (ALL) , and 1 aggressive natural killer cell leukemia (ANKL) . All patients received fludarabine, cytarabine and melphalan with rabbit anti-human thymocyte globulin (FAB+rATG regimen) and transplanted with high dose non-T cell-depleted peripheral hematopoietic stem cells from donors. Enhanced graft versus host disease (GVHD) prophylaxis and infection prevention were administered. Results: Fifteen days after transplantation, 16 patients achieved complete donor chimerism. One of them rejected the donor graft completely at thirty days after transplantation, and the other 2 patients had mixed chimerism 15 days after transplantation and converted to complete recipient chimerism at 30 days after transplantation. The cumulative incidence of acute GVHD (aGVHD) was 61.1% (95%CI49.6%-72.6%) . The incidence of grade Ⅱ-Ⅳ aGVHD was 35.4% (95%CI 21.1%-49.7%) , whereas grade III-IV was 13.8% (95%CI 4.7%-22.9%) . The 2-year cumulative incidence of chronic GVHD (cGVHD) rate was estimated at 38.2% (95%CI 25.5%-50.9%) . Patients were followed-up for a median of 14.5 months (range, 3-44 months) . The Kaplan Meier estimates of 2-year overall survival (OS) and disease-free survival (DFS) was 72.6% (95%CI 60.1%-85.1%) and 63.7% (95%CI 49.2%-78.2%) , respectively. The 2-year cumulative incidence of relapse and non-relapse-mortality (NRM) was 31.2% (95%CI 16.5%-45.9%) and 12.5% (95%CI 4.2%-20.8%) , respectively. Conclusion RIC-haplo-PBSCT protocol can achieve better results in patients with hematologic malignancies over 50 years old.

OBJECTIVETo study the clinical features of acute graft-versus-host disease (aGVHD) and its risk factors for the related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation (RHNT-PBSCT).

METHODSFrom July 2002 to December 2012, 104 patients who underwent the RHNT-PBSCT were enrolled to analyze the incidences, location and its risk factors of aGVHD, compared with those of the 103 patients who received the HLA-matched sibling non T cell-depleted in vitro PBSCT (MSNT-PBSCT) in the same period.

RESULTS(1)The cumulative incidence of aGVHD in the RHNT-PBSCT group was significantly higher than the MSNT-PBSCT group [(56.2±4.7)% vs (34±3.6)%, P<0.05], but the cumulative incidences of II-IV and III-IVgrade aGVHD had no significant difference between the two groups[(39.5±2.9)% vs (21.2±5.4)%, P>0.05; (12.6±4.1)% vs (10.8±2.4)%, P>0.05]. (2)The cumulative incidence of cutaneous aGVHD was significantly higher in RHNT-PBSCT group than that in MSNT-PBSCT group [(42.3±3.2)% vs (17.5±2.3)%, P<0.05]. The cumulative incidences of liver and gastrointestinal aGVHD between the two groups had no significant difference [(7.7±2.1)% vs (12.6±3.4)%, P>0.05; (16.3±4.5)% vs (10.3±2.5)%, P>0.05]. (3)The 3-year disease free survival (DFS) and overall survival(OS) of RHNT-PBSCT group and MSNT-PBSCT group were (63±5.5)%, (65.2±4.7)% and (74.2±5.4)%, (77.4±5)% respectively, without significance (P=0.078, P=0.052). (4)aGVHD occurrence with HLA haplotype (P=0.003) and matched loci (P=0.002) were significantly correlated by univariate analysis. Multivariate analysis showed that only the HLA typing is a risk factor for aGVHD (HR=1.891, P=0.03).

CONCLUSIONAlthough the incidence of total aGVHD in RHNT-PBSCT protocol is higher than that in MSNT-PBSCT, but there was no significance in severe aGVHD and cutaneous aGVHD was the common type, which indicates that RHNT-PBSCT protocol is feasible.

Disease-Free Survival ; Graft vs Host Disease ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; Humans ; In Vitro Techniques ; Incidence ; Peripheral Blood Stem Cell Transplantation ; Risk Factors ; Siblings ; T-Lymphocytes