Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Cerebral vascular disease has already become the first threat to Chinese people. Extracellular vesicles deliver multiple substances as microRNAs, and play roles in pathological processes of cerebrovascular diseases. In recent years, extracellular vesicles and microRNAs researches mainly focus on the protection of animal models, intervention of pathological processes and new biomarker researches. We summarize the research progress of extracellular vesicles in cerebrovascular disease from the above three aspects to provide new points and directions for early prevention and treatment of cerebrovascular disease.

Objective:To establish a mouse model of gastric cancer by inoculating MKN45 cells into mice with normal immune function utilizing microcarrier technology. Methods:A total of 60 male C57BL/6 mice were randomly divided into three groups, namely, 2D, con-trol, and 3D groups, according to the coculture system of MKN45 and microcarrier. The mouse models of gastric carcinoma were estab-lished by hypodermic injection. The time of tumorigenesis, rate of tumor formation, and pathological features were observed in each group. Results:In the 3D group, the time of tumor formation was short, whereas the rate of tumor formation was high (80%). No de-tectable tumor formations were observed in the 2D and control groups. HE and immunohistochemical staining of the transplantation tumor model showed evident characteristics of human gastric cancer. Conclusion:A human gastric cancer model in normal immune mice was successfully established. The onset and development mechanism of gastric cancer could be more effectively investigated in mice with normal immune function through this model. Moreover, a more valuable and new animal model for the research and devel-opment of anticancer drug was established.

Objective To analyze the genotypes and homology of MSP?1 and CSP gene of Plasmodium vivax in Shandong Province,so as to provide the evidence for case traceability. Methods A total of 12 blood samples were collected from P. vivax?infected cases in Shandong Province in 2011. Parasite genomic DNA was extracted. Primers were designed according to MSP?1 and CSP gene sequences of P. vivax. Then Nested PCR,enzyme digestion,sequencing and sequence alignment,and homolo?gous analysis were performed. Results The MSP?1 gene of all the 12 samples from P. vivax?infected cases were detected with a 470 bp PCR amplification band,and 350 bp and 120 bp enzyme digestion fragments,which were identified as type Sal?1. An analysis of phylogenetic tree of MSP?1 gene showed that the sequences of 9 indigenous case samples in Shandong Province were located in the same branch,one case sample infected from India was located in the same branch with India strains. All the 12 P. vivax?infected samples covered GDRA(D/A)GQPA sequences in CSP gene,which were identified as type PV?Ⅰ. Of the CSP gene among 12 P. vivax?infected samples,10 samples of indigenous case in Shandong Province and one sample of the case in?fected in Guangdong Province were detected with both 560-840 bp and 150-230 bp PCR amplification bands,which were iden?tified as temperate zone family strain of type PV?Ⅰ. However,one sample from the case infected in India was detected only with a 560-840 bp band,which was identified as tropical zone family strain of PV?Ⅰ. An analysis of phylogenetic tree of CSP gene showed that the sequences of 10 samples from the indigenous cases in Shandong Province and one sample from the case infected in Guangdong Province were located in the same branch,one sample from the case infected in India was located in the same branch with India and Indonesia strains. Conclusion Of all the indigenous isolates in Shandong Province,MSP?1 gene is geno?typed type Sal?1,CSP gene is genotyped temperate zone family strain of type PV?Ⅰ,with a high homology found among the in?digenous isolates.

This paper reports one case of atypical falciparum malaria imported from Africa,whose blood smear contains many large trophozoites,with punctiform or massive brown pigment granules,the body shape of the plasmodium is similar to that of Plas-modium vivax and Plasmodium ovale. After the gene detection by PCR,the case was diagnosed as falciparum malaria. As large tro-phozoites were rarely seen in the peripheral blood of non-severe falciparum malaria cases,much attention should be paid to the identification of Plasmodium falciparum and other plasmodia in microscopic examinations.

Objective To understand the status of intestinal parasitic infections and the related knowledge and behavior in residents of Jiaodong area of Shandong Province,so as to provide the evidence for making an appropriate preventive and control strategy. Methods A total of 18 villages from 6 counties in Jiaodong area were selected as investigation sites according to the stratified sampling method. The feces samples of the permanent residents aged above 3 years were collected and examined by Kato-Katz technique to find the intestinal parasite eggs,and the children under 12 years old were examined by the method of cellophane anal swab to detect the Enterobius vermicularis eggs. In addition,50 households in each survey sites were randomly selected to in-vestigate the basic family situation and the condition of awareness on prevention knowledge and formation of correct behavior of res-idents by using a structured questionnaire. Results Totally 6 163 residents involved in the feces examinations,and the total in-fection rate of intestinal parasites was 6.91%. The infection rates of Trichuris trichiura,Ascaris lumbricoides and hookworm were 6.56%,0.62%and 0.21%,respectively. The infection rate of E. vermicularis in children under 12 years old was 0.51%. The eggs of Clonorchis sinensis and Taenia solium were not found in this survey. The awareness rate of knowledge about preventing parasitic diseases was 49.54%. The formation rates of washing hands before eating,washing hands after using the toilet,never eating raw fruit and vegetable without washing clean,never working in the field with bare feet,and never drinking unboiled water were 97.78%,91.95%,88.81%,92.42%and 86.48%respectively. Conclusions The infection rate of intestinal parasites is low in Ji-aodong area,but there is a significant difference among different counties. The awareness rate of knowledge about preventing para-sitic diseases is low,but the formation rate of healthy behavior is high. In the future,the health education and the strategy of tak- ing medicine among the key population should be enhanced,and the project of reconstructing safe water supply and lavatory should be advanced.

Objective To construct a multi-gene recombinant pcDNA3-HBsAg-p30-ROP2 expression vector and identify it preliminarily. Methods According to recombinant pcDNA3-p30-ROP2 restriction sites,HBV HBsAg gene sequences of primers were designed and synthesized to amplify target fragment,and then cloned into pcDNA3-HbsAg-p30-ROP2 expression vector. Af-ter sequencing,it was identified finally by restriction enzyme digestion and other molecular biology techniques. Results HBV HBsAg gene segment was amplified by PCR and the multi-gene recombinant pcDNA3-HBsAg-p30-ROP2 expression vector was constructed and identified to be correct as theoretical values. The PCR and restriction enzyme digestion results showed that HBsAg and p30-ROP2 gene in recombinant plasmid were confirmed by DNA sequencing. Conclusion The multi-gene recombinant pcD-NA3-HBsAg-p30-ROP2 expression vector is successfully constructed.

Objective To discuss the effect of team-based learning(TBL)combined with net-work environment in pathological experiment teaching. Methods Totally 112 clinical medical under-graduates were selected as research object. Digital microscope interactive teaching platform under the network environment was used in experimental group(n=56). In pathology experiment teaching,TBL steps of training,teaching plan demonstrating,grouping,teaching task arranging,asking questions, group learning and communicating were implemented. Traditional method (lecture)was used in con-trol group (n=56). Teaching effect was analyzed through questionnaire survey and score analysis. Stu-dents' evaluation on TBL teaching and network environment resources was expressed as percentage. Results In experiment group,average score was (85.5±3.11)points and average final exam score was (83.8±2.53)points,while in control group,average final exam score was (76.4±11.89)points. There were significance differences between the two groups (t=7.018,P<0.01). Surveys showed that most students accepted TBL teaching combined with network environment. Conclusions TBL teach-ing combined with network environment is feasible and effective in the pathology experimental class. Students' learning enthusiasm is generally improved and effectiveness of TBL teaching is satisfactory.

Objective To study clinical application of femoral head exclusion after resection of pelvic tumors around acetabulum with less limb damage and complications.Methods From October 1999 to August 2009,18 patients with pelvic tumors around acetabalum (zone Ⅱ of Ennekingl were treated with tumor resection and femoral head exclusion,including 16 males and 2 females with an average age of 54 years(range,18-72).The diagnosis were chondrosarcoma(4 cases),osteosarcoma(2),giant cell tumor of bone(4),synoviosareoma(1),malignant fibrous histiocytoma(1),Ewing sarcoma(1),and metastatic carcinoma(5).Throe cases were treated by selective arterial embolization before operation and 4 cases by temporary block of lower abdominal aorta or common iliac arte.Regular follow-up in clinic was done to observe function of joint and radiographic imaging.Results All patients were followed up for 55 months(range,3-118).The mean surgical time was 170 min(range,120-350 min).The mean blood loss was 1200 ml(range,600-2200 ml).All wounds were healed without infection.One patient with osteosarcoma and 3 with metastatic carcinoma died of multiple organ metastases during 6 months to 2 years after operation.The others had no local relapse.The mean limb discrepancy was 5.0 cm (range,2.0-7.5 cm).The mean Enneking score was 23 (range,20-27).All patients needed custom-made shoes with heightened heel of 2-3 cm.Osteonecrosis of the femoral head was not found in radiographic images.Eight cases had formed artificial acetabulum.One case had gentle lumbar scoliosis.Conclusion The clinical application of femoral head exclusion after resection of pelvic tumors around acetabulum had low complications,less pain,low relapse,better function in the recent period.

To provide the basis for preparation of diagnostic kits and vaccines in Toxoplasma gondii infection, the gene coding for the qualified recombinant p30 protein (SAG1) of this parasite was amplified by PCR, and the amplified gene was cloned into prokaryotic expression vector pET-30a(+) to construct the recombinant plasmid, and then transformed to E.coli DH5α. The positive recombinant plasmid was screened by PCR and double enzymes digestion, and the nucleotide sequence of p30 gene was determined by automated DNA sequencing. Meanwhile, the identified recombinant plasmid was transformed to E.coli BL21(DE3) with the expression of p30 on bacteria induced by IPTG and the expressed protein was identified by SDS-PAGE. The protein obtained was then further purified and refolded, and its biological activity was checked by Western blotting. It was shown that the size of the amplified gene was 750 bp with molecular weight of 30 ku, and this protein could specifically react with monoclonal antibody against p30 protein.