OBJECTIVE:To discuss what service marketing strategies the pharmaceutical enterprises in China should choose in the face of more and more fierce competition in pharmaceutical markets.METHODS:The service characteristics of both prescription drugs and over-the-counter(OTC)drugs were analyzed and new conceptions in pharmaceutical marketing such as the development and application of the service marketing were introduced as well.RESULTS&CONCLUSION:Di?versity,standardization,materialization are the right way the pharmaceutical enterprises should follow in the prescription drugs services;however,standardization,mechanics,brands are necessary for the OTC drugs services.

Objective To develop a genetically modified fetal liver cells (FLC) based transplantation system that can release therapeutic levels of hematopoietic growth factors into the system circulation which can facilitate treatment of patient receiving cytokine therapy following chemotherapy. Method Examine adeno virus mediated gene transfer to isolated murine FLC and evaluate the biocharacterization of intrasplenic transplantation of gene modified murine FLC. Results Substantial transfection rate of 80%～85% were achieved at a ratio of 50 for 2 hr of exposure. Gene modified FLC (FLC GM) labeled with 111 In were injected into the allogenic mice, spleen, the %ID/g of liver was 20%～25% at 24 hr and 50%～55% at 48 hr after transplantation. In addition, serum concentration of GM CSF in mice with intrasplenic transplantation reached its maximum at 48 hr [(356 ?58 ) pg/ml]. Conclusion Intrasplenic transplantation of FLC GM can be predominantly localized in liver and spleen, and engraft rapidly and maintain normal function, which represent a critical step toward successfully accomplishing liver directed gene therapy.

BACKGROUND:For pediatric patients with aplastic anemia in China, it is difficult to find human leucocyte antigen-matched sibling donors that are mostly replaced by parental donors.
OBJECTIVE:To retrospectively analyze the clinical efficacy and safety of parental haploidentical peripheral blood hematopoietic stem cel transplantation in children with relapsed and refractory severe aplastic anemia.
METHODS:Seventeen children with relapsed and refractory severe aplastic anemia who had no matched sibling or unrelated donor and failed to respond to immunosuppressive therapy were subjected to parental haploidentical peripheral blood hematopoietic stem cel transplantation. A conditioning regimen of fludarabine+cyclophosphamide+rabbit anti-human thymocyte immunoglobulin antibody and the triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease.
RESULTS AND CONCLUSION: (1) Of the 17 children, 16 cases (94%) reached hematopoietic reconstitution, and the median time of neutrophils≥ 0.5×109/L and platelets≥ 20×109/L was 13 (11-15) days and 17 (12-28) days, respectively. (2) Incidence of acute graft-versus-host disease was 47% (8 of 17 cases), including 29% (5/17) of grades I-II and 18% (3/17) of grades III-IV. Incidence of chronic graft-versus-host disease was 41% (7/17). (3) With a median folow-up duration of 268 (43-753) days, the overal survival rate was 70.6% (12/17). Five dead cases (29%) belonged to transplantation-related death, including one case of fungal skin infections, one case of graft-versus-host disease, three cases of severe lung infection. No relapse case was reported. These findings indicate that if there are no matched sibling or unrelated donors and the immunosuppression effect is poor, parental haploidentical peripheral blood hematopoietic stem cel transplantation is a safe and effective salvage treatment for children with relapsed and refractory severe aplastic anemia.

Objective This study aims to investigate the application of the Plan-Do-Check-Act(PDCA)cycle in the Di-agnosis Related Group(DRG)payment system for oncological diseases.Methods We analyzed the factors influencing DRG pay-ment and incorporated the PDCA Cycle in the oncological diseases at a tertiary hospital in Tianjin.The baseline data of cases partic-ipating in DRG payment from April 2022 to September 2022 were compared with the settlement data of cases participating in DRG payment from October 2022 to March 2023.SPSS 20.0 was used to evaluate the impact of data quality in medical record documenta-tion on DRG admission rate,average hospitalization costs,average length of stay,Case Mix Index(CMI)value,and DRG settle-ment rate,so as to assess the effectiveness of the PDCA cycle in DRG payment within the oncological diseases at the hospital.Re-sults Following the PDCA cycle,the DRG admission rate increased from 84.03%to 89.98%,and the cases ineligible for inclu-sion decreased by 22.78%due to mismatched main diagnosis and procedures."Violations of the reporting and coding principles that do not require reporting"and"omission of primary surgical procedure codes"were no longer observed as reasons for failed DRG inclusion.Ambiguous cases with both average hospitalization costs and average length of stay higher than those of normal inclu-sion cases,leading to an increase in the average hospitalization cost from 22 496.56 yuan to 24714.92 yuan,and the average length of stay increased from 7.50 days to 8.13 days.The CMI value increased from 0.96 to 1.08,and the DRG settlement rate increased from 107.93%to 130.67%.Conclusion The PDCA cycle can effectively enhance the quality of medical record documentation,leading to improved quality in medical insurance settlement lists and DRG admission rates.It can help identify operational issues within the de-partment and promote the smooth implementation of DRG payment reform in the oncological department.

Objective To explore the application value of the Plan-Do-Study-Act(PDSA)cycle in reducing the occur-rence of decomposed hospitalization for stroke disease under the Diagnosis Related Group(DRG)payment model and validate the effectiveness of strategies to reduce decomposed hospitalization.Methods Taking stroke cases participating in DRG payment from January 2022 to December 2022 in a tertiary hospital in Tianjin as the baseline,the criteria for decomposed hospitalization were determined based on the"Implementation Rules for DRG/DIP Network Audit(Trial)"issued by the Tianjin Medical Insur-ance Fund Settlement Center.A PDSA cycle plan was developed according to the document content,and the PDSA cycle was im-plemented from January to December 2023.The relationship between the number of decomposed hospitalizations before and after the PDSA cycle was analyzed using SPSS 20.0 to determine the actual application effect.Results After the PDSA cycle,the number of decomposed hospitalizations decreased from1268 cases to26 cases,a total decrease of 97.95%.The number of cases in each target subgroup and the frequency of factors leading to decomposed hospitalization all showed a significant decrease.Con-clusion The PDSA cycle plays a significant role in addressing the problem of decomposed hospitalization for stroke disease under the DRG payment model.It can effectively reduce the occurrence of decomposed hospitalization,improve the quality of medical insurance settlement lists and medical records,and standardize clinical diagnosis and treatment behavior.

Regional party building has been an important exploration in innovating grassroots party building in recent years.Under the comprehensive implementation of the requirements for party building in the new era,public hospitals have a-chieved the sharing and extension of medical resources through system and mechanism reforms and innovations.Based on the re-gional party building,it has become an inevitable requirement to explore the new era of party building in public hospitals.This study analyzes the current challenges faced by hospitals participating in regional party building work and combines the practical experience of regional party building work in Shuguang Hospital,affiliated to Shanghai University of Traditional Chinese Medi-cine.It promotes paths such as party building leading joint construction,expanding the scope of medical volunteer services,and promoting the deep integration of party building and business work.This will further improve the quality of people's lives,ulti-mately achieving"mutual benefit"through"resource sharing."

Objective To We Used high-dose paraquat to induce apoptosis of A549 cells,and observed the expression of E-cadherin,α-SMA,caspase-8,caspase-3 and caspase-9.Then explored the possible mechanisms of apoptosis.Methods A549 cells were treated with various concentrations of PQ (0.1-1.0 mmol/L) for 24 and 48 hours,then observe the cell morphology and measured cell survival rate respectively determined by MTT method.A549 cells were treated with various concentrations of PQ (0.1,0.2,0.3 mmol/L) for 24 hours.The expressions of the mRNAs for α-SMA、E-cadherin,caspase-8,caspase-3 and caspase-9 were analysed by quantitative real-time PCR.Exposed to various concentrations of PQ (0.1,0.2,0.3mmol/L) for 24 hours,we analysed the protein expressions of α-SMA、E-cadherin、caspase-8、caspase-3 and caspase-9 by Western blot analysis.Results Treated with various concentrations of PQ (0.1-1.0mmol/L) for 24 hours,the A549 cells survival rate significantly reduced by MTT method.For 48 hours,the survival rate was lower.So,in subsequent experiments,we used 0.1,0.2 and 0.3 mmol/L concentration of paraquat to A549 cells,trained for 24 hours.After high-dose (0.1,0.2 and 0.3 mmol/L) exposure to PQ,a decrease in E-cadherin was observed while a decrease in α-SMA was also detected of the mRNAs.While the expressions of the mRNAs for caspase-8、caspase-3 and caspase-9 wereincrease.The protein expressions of α-SMA and E-cadherin were decrease with the increase of concen trations by Western blot analysis,and the levels of caspase-8、caspase-3 and caspase-9 were increase.Conclusions After high-dose short-time exposure to PQ,the survival rate of A549 cells is decreased obviously,cell morphology changed significantly,and the expressions of α-SMA and E-cadherin were decrease.But the expressions of caspase-8、caspase-3 and caspase-9 were increase.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

Objective:To detect the expressions of S100P, mucin 5A, mucin 6, estrogen-inducing protein pS2, C-reactive protein (CRP), N-cadherin and CD56 in intrahepatic cholangiocarcinoma (ICC) and to analyze the sensitivity and specificity in the diagnosis of large and small bile duct cholangiocarcinoma.Methods:Clinical data of 47 patients (22 patients small bile duct and 25 patients large bile duct ICC) diagnosed with ICC at Ningbo Clinical Pathology Diagnosis Center from January 2018 to September 2019 were retrospectively analyzed, including 29 males and 18 females, aged (64.0±11.1) years. Cancer tissue specimens were collected. The expressions of S100P, mucin 5A, mucin 6, estrogen-induced protein pS2, CRP, N-cadherin and CD56 in cancer tissues were detected by immunohistochemical method, and the sensitivity and specificity of these proteins in the diagnosis of small bile duct and large bile duct ICC were analyzed.Results:In 22 patients with small bile duct type ICC, CD56 expression was positive in 12 (54.5%), CRP expression in 22 (100.0%) and N-cadherin expression in 21 (95.5%), large bile duct type ICC were 8.0%(2/25), 28.0%(7/25), 40.0%(10/25). In 25 cases of large bile duct type ICC, S100 calcium-binding protein P expression was positive in 23 cases (92.0%), estrogen-induced protein pS2 expression in 21 (84.0%) and mucin 5A expression in 23 (92.0%), small bile duct type ICC were 9.1%(2/22), 36.4%(8/22), 0. The positive expression rates of CD56, CRP and N-cadherin in small bile duct type ICC were significantly higher than those in large bile duct type ICC, while S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A were lower than those in large bile duct type ICC (all P<0.05). The sensitivity of CD56, CRP and N-cadherin in the diagnosis of small bile duct type ICC were 54.5%, 100.0% and 95.5%, and the specificity were 92.0%, 72.0% and 60.0%, respectively. The sensitivity of S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A in the diagnosis of large bile duct type ICC were 92.0%, 84.0% and 92.0%, and the specificity were 90.9%, 63.6% and 100.0%, respectively. Conclusion:The positive expressions of CD56, CRP, N-cadherin, S100 calcium-binding protein P, estrogen-induced protein pS2 and mucin 5A are of great value in the differential diagnosis of large bile duct type and small bile duct type ICC, and the diagnostic accuracy is reasonable, which could facilitate the accurate histological classification of ICC.

Objective:To investigate the relationships between the expression level of human epidermal growth factor receptor 2 (HER2) in HER2-positive breast cancer and the characteristics of ultrasound imaging and mammography.Methods:The imaging data of 486 patients with HER2-positive breast cancer treated in the Harbin Medical University Cancer Hospital from January 2014 to December 2021 were retrospectively collected. The relationships between the expression level of HER2 and the imaging features of breast ultrasound and mammography were analyzed.Results:49.38% (240/486) of HER2-positive breast cancer patients were HER2 2+, and 50.62% (246/486) of HER2-positive breast cancer patients were HER2 3+. The age of HER2 2+ patients [ (52.88±1.16) years] was older than the age of HER2 3+ patients [ (49.59±1.00) years], and there was a statistically significant difference ( t=18.07, P<0.001) . There was a statistically significant difference of menstrual status between HER2 2+ patients and HER2 3+ patients ( χ2=4.42, P=0.036) . There were statistically significant differences in the ultrasonography showed burr sign ( χ2=8.37, P=0.010) , posterior echo ( χ2=9.68, P=0.017) , axillary lymph node enlargement ( χ2=15.77, P<0.001) between HER2 2+ patients and HER2 3+ patients. There was a statistically significant difference in the mammography showed whether there were lumps between HER2 2+ patients and HER2 3+ patients ( χ2=15.81, P<0.001) . Conclusion:The expression level of HER2 in HER2-positive breast cancer patients is related to burr sign, posterior echo, and axillary lymph node enlargement shown by ultrasound, as well as lumps shown by mammography, which can provide certain information for clinical prediction of malignant degree of breast cancer, prognosis and individualized treatment plan.