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 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 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.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Objective: To analyze the effectiveness and response status of China Infectious Disease Automated Alert and Response System (CIDARS) in Hunan province from 2012 to 2016 for improving the system. Methods: To collect the early warning signals, the number of suspected events, the result of on-site investigation, the signal response time and the result of public health emergencies, and the χ² test, correlation analysis and non-parametric test were used to analyze the information on CIDARS in Hunan Province during the period from 2012 to 2016. Results: A total of 108 188 signals were generated by the CIDARS in Hunan Province; The warning involved 30 kinds of infectious diseases and 138 counties (districts), and each county (district) received 3.00 weekly warning messages on average; 100% early warning signal was responded, 2 h response rate was 92.43%; The median response time (P25-P75) was 0.28 (0.11-0.77) h in the single case warning, and the five-year timely response rate showed an upward trend year by year (trend χ²=58.89, P<0.05); the median response time (P25-P75) was 0.56 (0.28~1.06) h in the time series warning, and the five-year timely response rate showed no trend (trend χ²=2.43, P>0.05); the time series warning response was more timely than the single case warning, and the difference between the two timely response rates was statistically significant(χ²=5156.60, P<0.05). The studies showed that the sensitivity, specificity, and detection timeliness of the system were 84.80%, 69.53%, and 2.80 d, respectively; There was no significant difference in the infectious diseases detecting timeliness of CIDARS(H=8.75, P>0.05); the system had the best effect in rubella, and the positive likelihood ratio of rubella is 4.36. Conclusions CIDARS in Hunan province runs well overall with high sensitivity and timely response to the early warning signals, but the specificity of the early warning system needs to be improved. The quality of the epidemic report of infectious diseases needs to be further improved, and the early warning parameters and warning method should be adjusted according to the characteristics of different diseases and the differences among different regions.

Objective:To summarize the treatments and outcomes of patients with chronic granulomatous disease (CGD), so as to improve the management of the disease and improve the quality of life of the patients.Methods:Clinical data of 82 children with CGD hospitalized at Children′s Hospital of Chongqing Medical University and born between January 1999 and December 2016 were collected.Patients were divided into the survival group and the death group.The general information, infectious events and inflammatory complications, as well as treatments and survival situations were analyzed.Results:Among the 82 cases, 55 cases (67.1%) were in the survival group and 27 cases (32.9%) were in the death group.Forty-nine (59.8%) cases developed manifestations in the neonatal period.Specifically, there was a statistically significant difference ( P<0.05) in the proportion of patients who deve-loped manifestations in the neonatal period between the death group (81.5%) and the survival group (49.1%). Fifty-eight (70.7%) cases started to receive Compound Sulfamethoxazole since diagnosis, with an average duration of 36.8 months.Fifty-two (63.4%) cases received Voriconazole or Itraconazole to prevent fungal infection, with an average duration of 34.3 months.There were 288 hospitalizations due to infections in total.The detection rate of bacteria, fungi and mycobacterium tuberculosis was 41.3%, and the rate in the death group (51.8%) was higher than that in the survival group (36.9%)( P<0.05). Klebsiella pneumoniae, Staphylococcus aureus, Burkholderia onion and Escherichia coli were the most frequent bacteria detected, among which Klebsiella pneumoniae and Escherichia coli were all exten-ded-spectrum β-lactamases positive.The use of advanced-antibiotics in the death group (70.4%) was higher than that in the survival group (40.0%) ( P<0.05). Seventeen (20.7%) cases developed inflammatory complications, mainly including interstitial lung disease or pulmonary fibrosis, inflammatory bowel disease and incomplete Kawasaki disease.Thirty-two (39.0%) cases received hematopoietic stem cell transplantation (HSCT), of which 25 patients (78.1%) were transplanted in Children′s Hospital of Chongqing Medical University, with a success rate of 96.0% (24/25 cases). The Kaplan-Meier survival curves showed a worse prognosis in those who developed manifestations in neonates, rely on advanced-antibiotics, and did not receive transplantations. Conclusions:The earlier the clinical manifestations appear, and the higher the utilization rate of advanced-antibiotics used, the more serious the condition is.Conservative treatment with drugs is still insufficient, and the emergence of drug-resistant bacteria increases the difficulty of managements.The recognition and treatments of inflammatory complications needs more explorations.HSCT is so far the only curative therapy for CGD in China.