Domestic generic drug registration has a large proportion in chemical drugs with outstanding repeated registration phe-nomenon and low level innovation of enterprises. Under the above background, chemical drug registration reform kicked off. The imple-mentation of new drug registration classification, marketing authorization holder and the changes of listed drug registration documents have a huge impact on China' s pharmaceutical industry, which can promote the reformulation of domestic pharmaceutical market, en-courage R&D and innovation in enterprises and accelerate the pace towards the international market.

OBJECTIVE:To provide reference for cultivating high-level comprehensive medical talents with high quality. METHODS:Based on the market and social needs,the teaching reform was conducted from the concepts of educational ideas, modes,curriculum system,contents,management and other aspects. RESULTS:In order to adapt to the needs of society and era, it should establish large education educational ideas to cultivate student's independent ability to obtain knowledge and self-develop-ment to make people change into community basic services and service and dedicate society with modes of cultivating inter-disci-plinary talents,including combination of prduction and study,foundation strengthening,professional expanding,penetration of sci-ence and technology and combination of arts and science;generally optimize curriculum system with theprinciple of precise defini-tion,clear classification,and optimized combination based on market and social needs;and update contents timely and teaching materials;the teaching management should be changed from closed off management of the past to the external management which dominated by the market assessment. CONCLUSIONS:Reform of medical higher education based on the market and social needs can cultivate the talents with high quality and comprehensive medical knowledge for the social needs,which is conductive to the de-velopment of medical industry.

Objective To investigate the clinical procedural performance of CT-guided needle biopsy for peritoneal lesions.Methods CT-guided needle biopsy was performed in 84 consecutive patients (M : F=26 : 58) with peritoneal lesions.Results Among 84 cases,60 lesions were malignant (55 metastatic tumor,4 mesothelioma,1 lymphoma) and 24 were benign (11 tuberculosis, 13 inflammation).3 cases failed to get clear pathologic diagnosis because of lost data.Diagnostic accuracy was 91.7% (77/84).The major complications were noted in 3 patients(1 with bleeding,2 ascites exosmosis).Conclusion CT-guided needle biopsy for retroperitoneal lesions is highly practical and useful,should be considered complementary in the investigation of abdominal lesions.

Objective To compare the RIFLE and AKIN diagnosis criteria for acute kidney injury ( AKI) in patients undergoing cardiac surgery. Methods Patients undergoing cardiac surgery from January 2004 to June 2007 were retrospectively evaluated. RIFLE and AKIN criteria were employed for the diagnosis and staging of AKI which occurred 7 d after cardiac surgery. The diagnosis sensitivity and precision for prediction of hospital mortality were compared between these two criteria. Results One thousand and fifty-six patients were included in this study. There was no significant difference between the prevalence of AKI after cardiac surgery diagnosed by RIFLE criteria and that diagnosed by AKIN criteria (29.55% vs 31.06%, P>0.05). There was no significant difference between the total hospital mortality and the hospital mortality of each stage of AKI diagnosed by RIFLE criteria and those diagnosed by AKIN criteria ( P > 0. 05). Logistic regression analysis suggested that the relative risk of hospital mortality for AKI was similar between patients diagnosed by AKIN criteria and those diagnosed by RIFLE criteria. The area under the ROC curve for hospital mortality was 0. 856 for RIFLE and 0.865 for AKIN in all patients (P<0.001). Conclusion Compared to RIFLE criteria, AKIN criteria do not improve the sensitivity of diagnosis and predictive ability of hospital mortality of AKI after cardiac surgery.

Objective To investigate the expression of metabotropic glutamate receptor (mGluR) in murine podocytes.Methods Conditional immortalized podocytes were used in the research.RT-PCR was used to estimate the mRNA expression.Western blotting,immunofluorescence staining and immunoelectron microscopy were employed to determine the protein production.EIA,EMSA and Western blotting were used to examine the cAMP generation and cAMP response element-binding protein (CREB) activation.Intracellular calcium was investigated using confocal microscopy.Results mGluR1 and 5 mRNA and protein were expressed in murine brain and podocytes.In glomeruli,most of mGluR1 expression located in podocytes and was expressed in the submembrane space of the podocytes.Podocytes treated with (S)-3,5-dihydroxyphenylglycine (DHPG,an agonist for mGluR1/5) rapidly generated cAMP and activated CREB.(RS)-1-Aminoindan-1,5-dicarboxylic acid (AIDA,a selective antagonist of mGluR1/5) and SQ22536 (an adenylate cyclase inhibitor),but not 2-aminoethoxydiphenyl borate (2-APB an antagonist of canonical transient receptor potential) blocked DHPG-induced cAMP generation and CREB activation.Following DHPG treatment,intracellular calcium level rose and was prevented by pre-treatment with AIDA and 2-APB.DHPG-induced calcium influx was also prevented by incubation with calcium-free medium.Conclusion Podocytes express functional mGluR1 and mGluR5.

Objective To investigate the incidence, risk factors and outcome of acute kidney injury (AKI) following cardiac surgeries. Methods Clinical data of 1056 patients undergoing open heart surgery in Renji Hospital from January 2004 to June 2007 were retrospectively analyzed. Univariate and multivariate analyses were used to evaluate possible pre-,intra-, and post-operative parameters associated with AKI according to AKI Network (AKIN). Results Of the 1056 patients, 328 (31.06%) developed AKI. In-hospital mortality was 4.07% in all discharges while 11.59% in AKI patients (P<0.01). Multivariate logistic regression analysis revealed that increased age (OR=1.40), pre-operative hyperurieemia (OR=1.97), pre-operative left ventricular insufficiency (OR=2.53), combined surgery (OR=2.79), prolonged operation time (OR=1.43), post-operative circulation volume insufficiency (OR=11.08) were risk factors of AKI. Conclusions AKI is a common complication and associated with increased mortality following cardiac surgery. Increased age, pre-operative hyperuricemia, pre-operative left ventricular insufficiency, combined surgery, prolonged operation time, post-operative circulation volume insufficiency are useful in stratifying risk factors for the development of AKI.

Autophagy plays an important dual role in the occurrence and development of acute leukemia, inducing the apoptosis of leukemia cells to suppress the development of acute leukemia, and protecting the leukemia cells to sustain the survival and to resist the apoptosis induced by chemotherapy drugs. Some studies have showed that the drug sensitivity of acute leukemia cells can be improved by regulating autophagy to induce the apoptosis of leukemia cells, and thus, regulating autophagy is expected to be an effective therapeutic strategy of refractory/relapsed acute leukemia. This article reviews the recent progress of autophagy and acute leukemia treatment.

Objective:The aim of this study was to determine the colonization rate of carbapenem-resistant Enterobacterales (CRE) and identify the proportion and risk factors for bloodstream infection.Methods:This was a retrospective study conducted at the Department of Clinical Laboratory, Peking University People′s Hospital from January 2018 to December 2021. A total of 4 993 patients underwent rectal swab CRE screening for CRE, of which 137 were found to be positive. Clinical and laboratory data of the positive patients were collected, and the following parameters were analyzed: the positive rate of CRE screening in high-risk population, the species of colonized bacteria, antimicrobial resistance and the risk factors of CRE bloodstream infection in colonized patients. Statistical analysis was performed using SPSS 26.0 software. Univariate analysis was conducted using the chi-square (χ 2) test, while multivariate analysis was performed using binary logistic regression. The results were expressed as relative risk (odds ratio, OR) and 95% confidence interval ( CI). A significance level of 0.05 was considered statistically significant. The drug resistance rate of pathogen was analyzed by WHONET 5.6 software. Results:During the study period, a total of 4 991 patients who underwent rectal swab screening were eligible for inclusion, of which 137 patients were screened positive, resulting in a positive rate of 2.7% (137/4 991). The positive rates were higher in the intensive care ward and hematology ward, with rates of 5.5% (27/493) and 3.3% (109/3 321), respectively. A total of 145 colonization strains were isolated from patients with positive CRE screening, including 63 strains of Klebsiella pneumoniae (43.4%, 63/145), 52 strains of Escherichia coli (35.9%, 52/145), 16 strains of Enterobacter cloacae (11.0%, 16/145) and 14 strains of other Enterobacterales (9.7%, 14/145). The metal β-lactamase production type was the main component of CRE positive colonizing bacteria. The antimicrobial resistance of 145 strains to 22 antibacterial agents revealed that amikacin and tigacycline were the most sensitive. Among 137 CRE screening-positive patients, 14 (10.2%, 14/137) developed bloodstream infection. The isolated pathogenic bacteria included 10 Klebsiella pneumoniae strains and 4 Escherichia coli strains, with a predominant serine carbapenemase producing. Notably, the enzyme type and antimicrobial resistance of the bloodstream infection isolates in the same patient were highly consistent with those of the previous screening strains. Comparison was made between patients with positive CRE screening and those with CRE conversion to bloodstream infection. The unifactor analysis revealed significant differences in surgical history, neutropenia, hematopoietic stem cell transplantation, history of antibiotic use before rectal swab screening, screening within 48 hours after admission, and serine carbapenemase production by strains ( P<0.05). The multivariate analysis indicated that surgical history ( OR 24.659, 95% CI 2.540-239.411, P=0.006) and neutropenia ( OR 93.796, 95% CI 6.294-1 397.804, P=0.001) remained significantly associated with the risk of CRE bloodstream infection ( P<0.05). Conclusions:The CRE colonization rate was low in our hospital, but the proportion of patients with positive screening converted to bloodstream infection was high. Surgical history and neutropenia are risk factors for bloodstream infection transmission. Thus, it is essential to enhance monitoring in high-risk areas and susceptible patients.

Objective To explore the effect of tea polyphenols on the growth of human papillomavirus 16 (HPV16) subgenes-immortalized human cervical epithelial cells (H8 cells).Methods Cultured H8 cells were divided into 5 groups to be treated with 0 (control group),6.25,12.5,25 and 50 mg/L tea polyphenols respectively for 24,36,and 48 hours,and then cell counting kit-8 (CCK8)assay was performed to detect cell proliferation.After 24 hours of incubation,flow cytometry was conducted to detect cell apoptosis and cell cycle,and fluorescence microscopy to observe the morphology of apoptotic cells.Results After incubation with tea polyphenols at different concentrations for 24,36 and 48 hours,the proliferation of H8 cells was inhibited,and 12.5 mg/L tea polyphenols could inhibit the relative growth rate of H8 cells in a time-dependent manner.Flow cytometry showed that there was a significant difference in cell apoptosis rate among the 6.25-,12.5-,25-,50-mg/L tea polyphenols groups and the control group (52.62％ ± 0.62％,52.22％ ± 0.72％,42.52％ ± 0.90％,45.96％ ± 2.11％,29.96％ ± 0.70％ respectively,F =272.0,P ＜ 0.05).Moreover,all the tea polyphenol groups showed significantly increased cell apoptosis rate compared with the control group (all P ＜ 0.05).Fluorescence microscopy showed karyopyknosis,nuclear fragmentation and other typical apoptotic morphological changes in H8 cells in tea polyphenols groups.There were significant differences in the percentage of cells in G1,G2 phase and cell proliferation index among the 5 groups (all P ＜ 0.05).Compared with the control group,the 6.25-,12.5-,25-mg/L tea polyphenols groups showed significantly increased percentage of cells in G1 phase (55.96％ ± 0.72％,54.12％ ± 3.20％,65.30％ ± 1.51％ respectively,all P ＜ 0.05),but significantly decreased percentage of cells in G2 phase (3.17 ± 1.82％,4.94 ± 1.46％,4.65 ± 4.26％ respectively,all P ＜ 0.05) and lower cell proliferation index(0.44 ± 0.01,0.46 ± 0.02,0.36 ± 0.01 respectively,all P ＜ 0.05).Conclusion Tea polyphenols can inhibit the proliferation of H8 cells,induce cell apoptosis,and block cell cycle progression.

Objective:To evaluate whether the time to positive (TTP), handling time after positive alarm and turnaround time (TAT) of bacteremia blood culture can be shortened by optimizing blood culture workflow.Methods:This study was conducted retrospectively. Positive blood culture samples collected from Peking University People′s Hospital from January 1, 2014 to June 30, 2021 were analyzed in stages. In the traditional process stage of this study (2014), 502 bottles of positive blood culture samples were included in the analysis. In the first stage of process optimization (2016), the working time of staff was increased to 22:00, and 976 positive blood culture specimens were included in the analysis. In the second stage of process optimization (2018), the rapid identification process of MALDI-TOF MS was added, and a total of 1 029 bottles of positive blood culture samples were included. In the third stage of process optimization (2020) with the introduction of the new VIRTUO BACT/ALERT system. The difference of TTP, handling time after positive alarm and TAT of whole process in different stages of traditional process and process optimization were compared. All data were statistically significant when P<0.05 using rank-sum test. Results:In the traditional process stage (2014), the median quartile time of handling time after positive alarm was 55.70 (47.35, 68.45) h. In the first stage of process optimization (2016), the median quartile time of handling time after positive alarm was 47.25 (33.88, 59.96) h, and the handling time after positive alarm in the first stage of process optimization was significantly shorter than that in the traditional process stage ( Z=?10.734, P<0.001). In the second stage of process optimization (2018), the median quartile time for handling time after positive alarm was 47.18(36.41, 59.40) h, and 12.18% of the preliminary identification results of Gram-negative bacilli before 17:00 could be reported to the clinic before audit. In the third stage of process optimization (2020), the median quartile of TTP and TAT were 39.56 (21.52, 62.65) h and 78.16(64.68, 99.72) h respectively in the original BACT/ALERT 3D system. The new VIRTUO BACT/ALERT system had a median quartile of 37.03(21.08, 58.22) h for TTP and 73.41(62.88, 89.48) h for TAT. VIRTUO BACT/ALERT 3D had a significantly shorter TTP than BACT/ALERT 3D ( Z=?2.273, P=0.023), the TAT of VIRTUO BACT/ALERT system was significantly shorter than that of BACT/ALERT 3D system ( Z=?4.040, P<0.001). Conclusion:By improving the blood culture process of microbiology laboratory in many aspects and measures, the processing time of blood culture in each stage can be shortened and clinical benefits can be obtained.