ObjectiveTo investigate the neuroprotective effect of glycosides of cistanches （GCs） in 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）-induced Parkinson’s disease （PD） model mice and its potential mechanism. MethodsForty mice were randomly divided into control group， PD group， GCs group and levodopa （L-DOPA） group， with 10 mice in each group. The control group received intraperitoneal injection of normal saline， while the other groups were intraperitoneally injected with MPTP （30 mg/kg） once daily for 5 consecutive days. After model establishment， the control group and PD group were intragastrically administered normal saline， and the GCs group and L-DOPA group received intragastric administration once daily for 28 consecutive days， at doses of 100 mg/kg and 50 mg/kg， respectively. The open field test and rotarod test were used to evaluate motor function. Immunohistochemistry was performed to detect the number of tyrosine hydroxylase （TH）-positive neurons in the substantia nigra of the midbrain. Transmission electron microscopy was adopted to observe the ultrastructure of mitochondria in the substantia nigra. Biochemical assays were used to determine the levels of glutathione （GSH）， malondialdehyde （MDA）， total superoxide dismutase （T-SOD） and reactive oxygen species （ROS） in substantia nigra tissues. Western blot was applied to detect the protein expression of TH， nuclear factor erythroid 2-related factor 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap-1） and heme oxygenase-1 （HO-1） in substantia nigra tissues. ResultsCompared with the control group， mice in the PD group exhibited markedly impaired motor function， significantly decreased T-SOD activity， obvious reductions in the number of TH-positive neurons and GSH content， as well as elevated MDA and ROS levels in the substantia nigra （P<0.01）. Compared with the PD group， mice in the GCs group showed improved motor function， increased T-SOD activity， higher number of TH-positive neurons and elevated GSH content， accompanied by decreased MDA and ROS levels （P<0.05）. In the control group， mitochondria in the substantia nigra displayed normal morphology without obvious blurred membrane structures or vacuolar degeneration. The PD group presented mitochondrial swelling， disordered cristae and vacuolar changes， whereas these mitochondrial pathological alterations were alleviated in the GCs group. Compared with the control group， the protein levels of TH， Nrf2 and HO-1 were significantly downregulated， while Keap-1 protein expression was markedly upregulated in the PD group （P<0.01）. Compared with the PD group， the GCs group showed significant upregulation of TH， Nrf2 and HO-1 protein levels and a notable reduction in Keap-1 protein level （P<0.05）. ConclusionGCs ameliorate motor dysfunction and attenuate dopaminergic neuronal and mitochondrial damage in MPTP-induced PD model mice. These effects may be associated with modulation of Nrf2/HO-1 pathway-related protein expression， enhancement of antioxidant capacity， and alleviation of oxidative stress.

Objective To compare the efficacies of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in the treatment of post-chronic aplastic anemia(CAA)myelodysplastic syndrome(MDS)and primary MDS.Methods A retrospective analysis was conducted on 32 patients who received allo-HSCT treatment in Department of Hematology,North China University of Science and Technology Affiliated Hospital between Feb.2012 and Feb.2022,including 12 patients with post-CAA MDS and 20 patients with primary MDS.The overall survival rate,cumulative incidence of relapse(CIR)rate,non-relapse mortality(NRM)rate,and event-free survival rate were compared between the 2 groups.Results The median follow-up time for CAA to progress to MDS was 120(72-180)months.All the patients were followed up for 36(3-79)months after allo-HSCT.The 3-year overall survival rate of the post-CAA MDS group was significantly higher than that of the primary MDS group(83.8%vs 45.0%,P=0.035).The 3-year CIR of the post-CAA MDS group was significantly lower than that of the primary MDS group(16.7%vs 55.0%,P=0.021).There was no significant difference in the event-free survival rates or NRM rates between the 2 groups(both P＞0.05).Conclusion The post-CAA MDS patients have better survival after allo-HSCT than the primary MDS patients.Early allo-HSCT treatment may improve the prognosis.

Objective To develop a teaching strategy which is suitable for training talents and improving teaching quality in field of clinical gynecological oncology.Methods Seventy-eight clinical students of grade 2020 in a medi-cal university were divided into control group(n=38)and research group(n=40).The"3+2"teaching mode of team-based learning(TBL)and workshop(WS)were adopted,and the learning outcome was evaluated at preview preparation,knowledge application and the questionnaire survey of students,so as to promote the cultivation of clinical reasoning of medical students.Results Compared with traditional teaching method,TBL+WS teaching group had better academic performance.The difference of before class tests and final exams was more significant[17.53±6.15 points and(76.81±5.10)points,respectively,P＜0.001].However,among the eight dimensions of the classroom teaching questionnaire,the teaching quality dimension was the highest(97.5%).More students think that this model had a positive effect on cultivating clinical thinking and developing new knowledge.Conclu-sions This integrated teaching strategy improves the quality of obstetrics and gynecology teaching and suppots students'capacity building on clinical reasoning.

Network Meta-analysis was used to compare the efficacy and safety of Chinese patent medicines in the treatment of unstable angina pectoris. PubMed, Cochrane Library, CNKI, Wanfang, VIP and other databases were retrieved by computers from the establishment of the databases to June 2020. Randomized controlled trials(RCTs) of Chinese patent medicines for the treatment of unstable angina pectoris were collected. Two investigators independently screened out the literatures, and extracted data according to the inclusion and exclusion criteria. The quality of the included RCTs was evaluated according to the bias risk assessment tool recommended by the Cochrane System Reviewer Manual, and the Stata 13.0 software was used for data analysis and mapping. Through screening, 28 eligible studies were finally included, with the sample size of 2 885 cases, involving 8 Chinese patent medicines. The results of the network Meta-analysis showed that in terms of total effective rate for angina symptom improvement, the order was as follows: Shenshao Capsules > Naoxintong Capsules > Ginkgo Ketone Ester Dripping Pills > Compound Danshen Dripping Pills > Ginkgo Leaf Tablets > Shexiang Baoxin Pills > Tongxinluo Capsules > Yindan Xinnaotong Soft Capsules; in terms of total effective rate for ECG curative effect, the order was as follows: Ginkgo Ketone Ester Dripping Pills>Compound Danshen Dripping Pills > Tongxinluo Capsules > Shenshao Capsules > Shexiang Baoxin Pills > Yindan Xinnaotong Soft Capsules; in terms of hypersensitivity-C-reactive protein curative effect, the order was as follows: Tongxinluo Capsules > Shenshao Capsules > Ginkgo Leaf Tablets>Compound Danshen Dropping Pills> Shexiang Baoxin Pills > Naoxintong Capsules > Yindan Xinnaotong Soft Capsules > Ginkgo Ketone Ester Dropping Pills. Chinese patent medicine combined with conventional therapy can improve the clinical efficacy of unstable angina pectoris. Due to the differences in the quantity and quality of the included studies, the order results of Chinese patent medicines need to be further verified.
Angina, Unstable/drug therapy* ; China ; Drugs, Chinese Herbal ; Humans ; Medicine, East Asian Traditional ; Network Meta-Analysis ; Nonprescription Drugs

This study aims to compare the prostate cancer detection rate between magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) cognitive fusion targeted biopsy and systematic biopsy. A total of 614 patients who underwent transrectal prostate biopsy during 2016-2018 with multiparametric magnetic resonance imaging (mpMRI) were included. All patients with a PI-RADS V2 score ≥ 3 accepted both targeted biopsy and systematic biopsy, and those with a PI-RADS V2 score ≤ 2 only accepted systematic biopsy. Overall prostate cancer detection rate between the two biopsies was compared. MRI-TRUS cognitive fusion targeted biopsy identified 342 cases (75.7%) of prostate cancer while systematic biopsy identified 358 cases (79.2%). There was no significant difference in the detection rate between the two groups ( = 1.621, = 0.203). Targeted biopsy had significant fewer biopsy cores compared with systematic biopsy, reducing (9.3 ± 0.11) cores ( < 0.001) in average. Targeted biopsy had about 10.8% ( < 0.001) more tumor tissues in positive cores compared with systematic biopsy. The results show that both MRI-TRUS cognitive fusion targeted biopsy and systematic biopsy have good detection rate on prostate cancer. Cognitive targeted biopsy may reduce biopsy cores and provide more tumor tissues in positive cores.
Biopsy ; methods ; Humans ; Image-Guided Biopsy ; Magnetic Resonance Imaging, Interventional ; Male ; Prospective Studies ; Prostatic Neoplasms ; diagnostic imaging ; Ultrasonography, Interventional

Objective: To assess the diagnostic rate, safety and clinical application of percutaneous renal masses biopsy for advanced renal cell carcinoma patients.Methods: In this retrospective study, we collected the data of renal masses from the patients who underwent renal masses biopsy under ultrasound from April 2001 to December 2014 in Peking University First Hospital.A total of 75 patients who were undiagnosed or diagnosed with advanced renal cell carcinoma by the imageological method were enrolled in this study.The patient and lesion characteristics such as tumor size, pathology of tumor, histologic subtype, pathological grade, biopsied location and biopsied cores were recorded and analyzed.Results: Among all the 75 patients, biopsy was diagnostic in 64 cases (85.3%) and non-diagnostic in 11 cases (14.7%).Of the 64 diagnostic biopsies, 60 were malignant, including 37 (61.7%) renal cell carcinoma (RCC), 13 (21.7%) urothelial carcinoma and 10 (16.7%) other malignant masses.Of all the RCC subjects, 24 suffered from clear cell RCC, 5 papillary RCC, 3 collecting duct carcinomas, 1 unclassified RCC and 4 unknown subtypes.The 11 non-diagnostic biopsied samplings included inflammatory, blood and extrarenal tissue and normal renal tissue.The proportion of collecting duct carcinoma in RCC was 10.8% and the proportion of squamous carcinoma in urothelial carcinoma was 23.1%, which were both higher than the previous research findings.For the male and female groups, non-diagnostic yields were 6.5% and 30.4%, respectively (P=0.022).Of all the 75 patients, 13 renal cell carcinoma patients underwent the surgical treatment and got the results of postoperative pathology.Comparing preoperative biopsy pathological diagnosis with postoperative pathological diagnosis, we found the diagnostic correct rates for benign and malignant lesions, pathological subtype and pathological grade were 100%, 81.8% and 60%, respectively.Mild macroscopic hematuria occurred in 1 case after RMB and there were no serious complications in all the cases.Conclusion: Percutaneous renal masses biopsy under ultrasound with a high diagnostic rate which can define the histologic subtype of renal cell carcinoma.With targeted therapy, more and more patients whose evaluation suggests local advanced disease or metastatic tumors adopt renal tumor biopsy to define the histologic subtype, which could avoid unnecessary surgical treatment.

New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.

CYP2D6 is an important drug-metabolizing enzyme. The polymorphism of CYP2D6 leads to metabolism difference and the different reactions of drugs in the individuals and different races are normal phenomenon in clinical medication. CYP2D6*10 is an important subtype in Asian people and 51.3% Chinese are classified with this subtype. To obtain recombinant active CYP2D6*1/CYP2D6*10 in baculovirus system by optimizing coexpression with CYPOR, and detect their activity to catalyze dextromethorphan, three recombinants pFastBac-CYP2D6*1, pFastBac-CYP2D6*10 and pFastBac-CYPOR were constructed and transformed into DH10Bac cell to obtain the recombinant Bacmid-CYPOR, Bacmid-CYP2D6*1 and Bacmid-CYP2D6*10. And then the recombinant CYP2D6*1 and CYP2D6*10 virus were obtained by transfecting Sf9. Then homogenate protein activity was determined with dextromethorphan as substrate. The multiple of infection (MOI) and its ratio of recombinant CYP2D6 virus to CYPOR virus were adjusted by detecting the activity of the homogenate protein. The Km and Vmax are 26.67 +/- 2.71 micromol x L(-1) (n=3) and 666.7 +/- 56.78 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*1 to catalyze dextromethaphan. The Km and Vmax are 111.36 +/- 10.89 micromol x L(-1) (n=3) and 222.2 +/- 20.12 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*10 to catalyze dextromethorphan. There is significant difference between CYP2D6*1 and CYP2D6*10 for Vmax and Km (P < 0.01). The clearance ratio of CYP2D6*1 is 25.0 and the clearance ratio of CYP2D6*10 is 2.0. The expressed CYP2D6*1 and CYP2D6*10 are useful tools to screen the metabolism profile of many xenobiotics and endobiotics in vitro, which are benefit to understand individual metabolism difference.

OBJECTIVETo investigate the role of cell adhesion molecule in the development and extramedullary infiltration (EI) of acute leukemia.

METHODSThe expressions of neural cell adhesion molecule (NCAM) gene, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) genes in 25 acute leukemia patients bone marrow cells were detected by microarray and reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSThe expressions of NCAM, ICAM-1 and VCAM-1 gene were significantly higher in acute leukemia cells and leukemia cells with EI than in normal tissues and leukemia cells without EI, respectively, both by cDNA microarray and by RT-PCR.

CONCLUSIONThe cDNA microarray is a powerful technique in analysis of acute leukemia cells associated genes. High expressions of cell adhesion molecule genes might be correlated with leukemia pathogenesis and infiltration of acute leukemia cell.

Acute Disease ; Adolescent ; Adult ; Aged ; Bone Marrow Cells ; metabolism ; pathology ; Cell Adhesion Molecules ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; Leukemia, Myeloid ; genetics ; pathology ; Male ; Middle Aged ; Neural Cell Adhesion Molecules ; genetics ; Oligonucleotide Array Sequence Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; pathology ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Cell Adhesion Molecule-1 ; genetics

Objective To analyze the cause for complications of the long bone fractures treated with the interlocking nail and indicate the prevention and treatment measures. Methods From January 1998 to May 2000,168 patients with long bone fractures were treated with the interlocking nail. Of them, there were 77 cases of femoral fractures, 67 tibial fractures and 24 humeral fractures. Results All patients were followed up for 5-24 months. Complications occurred in 14 cases (8.33%) including 4 cases of infections, 1 lower limb necrosis, 2 internal fixation failure due to incorrect indication, 2 re-fractures during the operation, 2 distal screw misinserted,1 nail into the ankle joint, 1 distal screw broken and 1 distal screw loosening. Conclusions We should attach great importance to the following points during treatment of long bone fractures with interlocking nail:(1) The indications must be correctly handled. (2) The technique for interlocking nail must be performed strictly during operation; close inserting nail is proposed.(3) As for the comminuted fractures, bone continuity should be reconstructed and the time to start weight bearing properly delayed. (4) C-Arm X-ray supervision is necessary during operation.