ObjectiveTo determine the prevalence of ticks parasitic on domestic animals in Yiwu City of Zhejiang Province. MethodsWe monitored， identified and analyzed ticks parasitic on domestic animals in Yiwu in 2021. ResultsA total of 452 domestic animals were monitored， of which 306 were infected with ticks， suggesting a prevalence of 67.70%. A total of 2，603 ticks were captured， and the tick index was determined to be 5.76. The ticks were identified to belong to one family， four genera， and 10 species. Haemaphysalis longicornis was the dominant tick （59.16%）， followed by Rhipicephalus haemaphysaloides （26.32%） and Rhipicephalus microplus （6.45%）. Prevalence of ticks， tick index， and number of tick species were listed for domestic animals as follows： goats （74.37%， 7.45， 7 species）， yellow cattle （62.50%， 4.14，6 species）， and dogs （54.62%， 2.59， 8 species）. Moreover， goat was the main domestic animal infected with more than two tick species （25.99%）； H.longicornis （91.26%） was the species with most repated infections. The dominant species of ticks were H.longicornis （65.15%） and R.haemaphysaloides （29.42%） in goats， R.microplus （67.67%） and R.haemaphysaloides （20.69%） in yellow cattle， and H.longicornis （57.14%） and Haemaphysalis porcupines （21.10%） in dogs. However， seasonal fluctuation in tick index differed among goats， yellow cattle and dogs. The fluctuation in tick index in goats and dogs was consistent with that of H.longicornis， with a major peak in March and the minor peaks in September and October. The fluctuation in tick index in yellow cattle was consistent with that of R.microplus， with two peaks in April and August-September. In addition， larval ticks， nymphal ticks and adult ticks were caught in this study， among which nymphal ticks were most common. We found that single domestic animals were infected with ticks of the same species and different stages， which was more common in goats and those animals infected with H.longicornis. ConclusionTicks parasitic on domestic animals are common in Yiwu. Multiple species of ticks have been identified， with H.longicornis as the dominant species. It warrants further monitoring and countermeasures.

Objective:To investigate the correlation between plasma microRNA (miR)-122, miR-33a and the severity of coronary artery disease in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease.Methods:The clinical data of 196 patients with T2DM from January 2019 to October 2021 in Xuzhou First People′s Hospital were retrospectively analyzed. Among them, 81 cases were complicated with coronary heart disease (combined group), 115 cases were not complicated with coronary heart disease (control group). The plasma levels of miR-122 and miR-33a were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction, the plasma level of N-terminal B-type natriuretic peptide precursor (NT-proBNP) was detected by enzyme-linked immunosorbent assay. In combined group, the number of coronary artery lesions was determined according to the results of coronary angiography, and Gensini score was evaluated. Linear regression model was used to analyze the relationship between plasma miR-122, miR-33a and NT-proBNP levels with the incidence of coronary heart disease in patients with T2DM. Receiver operating characteristic (ROC) curve was used to analyze the plasma miR-122 and miR-33a in predicting efficiency of coronary heart disease in patients with T2DM. In combined group, Spearman correlation method was used to analyze the relationship between plasma miR-122, miR-33a and the number of coronary artery lesions, and Pearson correlation method was used to analyze the relationship between plasma miR-122, miR-33a and plasma NT proBNP, Gensini score.Results:The plasma miR-122, miR-33a and NT-proBNP in combined group were significantly higher than those in control group: 5.76 ± 1.35 vs. 1.18 ± 0.33, 1.39 ± 0.37 vs. 0.65 ± 0.11 and (786.87 ± 156.39) ng/L vs. (103.45 ± 19.27) ng/L respectively, and there were statistical differences ( P<0.01). Linear regression result showed that plasma miR-122, miR-33a, and NT-proBNP were positive correlation with occurrence of coronary heart disease in patients with T2DM ( P<0.01); ROC curve analysis result showed that the area under curve of plasma miR-122, miR-33a and combination in predicting coronary heart disease in patients with T2DM were 0.816, 0.845 and 0.912 respectively (95% CI 0.744 to 0.865, 0.768 to 0.892 and 0.836 to 0.967). Coronary angiography result showed that there were 46 cases of single vessel lesions, 25 cases of double vessel lesions and 10 cases of three vessel lesions. The plasma miR-122, miR-33a, NT-proBNP and Gensini score in patients with three vessel lesions were significantly higher than those in patients with double vessel lesions and patients with single vessel lesions: 6.52 ± 0.96 vs. 4.95 ± 0.85 and 3.74 ± 0.52, 1.45 ± 0.31 vs. 1.06 ± 0.25 and 0.81 ± 0.13, (829.78 ± 62.59) ng/L vs. (627.48 ± 47.12) and (502.64 ± 38.24) ng/L, (63.89 ± 12.71) scores vs. (42.18 ± 6.03) and (22.36 ± 2.41) scores, the indexes in patients with double vessel lesions were significantly higher than those in patients with single vessel lesions, and there were statistical differences ( P<0.05). In combined group, Spearman correlation analysis result showed that the plasma miR-122 and miR-33a were positive correlation with the number of coronary artery lesions ( r = 0.879 and 0.825, P<0.05); Pearson correlation analysis result showed that the plasma miR-122 and miR-33a were positive correlation with the plasma NT-proBNP and Gensini score (miR-122: r = 0.896 and 0.788, miR-33a: r = 0.871 and 0.765; P<0.05). Conclusions:The plasma levels of miR-122 and miR-33a are related to the occurrence of coronary heart disease and severity of coronary artery disease in patients with T2DM, which may be used to guide the prevention and treatment of coronary heart disease in patients with T2DM.

Radiotherapy following breast conserving surgery is a standard treatment in early stage breast cancer, and tumor bed delineation is a very important part of radiotherapy. Traditionally, operative record, preoperative ultrasound, postoperative scar, clips and other conventional methods were used to contour tumor bed in clinical, but they still have many limitations. In recent years, there were some progress in tumor bed delineation of the new style of lumpectomy cavity filling, preoperative/postoperative MRI images with CT images and other new methods. It is expected to solve the lack of postoperative tumor bed delineation consensus and standard in the future.

Objective To observe the long-term effect,adverse reaction and cosmetic outcome of early-stage breast cancer with hypofractionated whole-breast irradiation (HF-WBI) after breast-conserving surgery.Methods A total of 206 patients with stage 0-Ⅱ breast cancer after breast-conserving surgery were included in Shandong Cancer Hospital Affiliated to Shandong University from May 2014 to August 2017.According to radiotherapy fraction,patients were divided into HF-WBI group and conventional whole-breast irradiation (CF-WBI) group.In HF-WBI group,116 patients received whole-breast radiation to 42.56 Gy in 16 fractions followed by tumor bed boost of 9 Gy in 3 fractions or 10 Gy in 5 fractions.In CF-WBI group,90 patients received whole breast radiation to 50 Gy in 25 fractions followed by tumor bed boost of 10 Gy in 5 fractions.The 2-year local recurrence rate,2-year mortality rate,acute adverse reaction,late adverse reaction and cosmetic outcome of the two groups were analyzed.Results The 2-year local recurrence rates of HF-WBI group and CF-WBI group were 0.86％ (1/116) and 2.22％ (2/90) respectively,and there was no significant difference between the two groups (x2 =0.049,P =0.824).The 2-year mortality rates of the two groups were 0.86％ (1/116) and 0 (0/90) respectively,and there was no significant difference (P ＞ 0.999).There were 108 cases (93.1％) in HF-WBI group and 84 cases (93.3％) in CF-WBI group with grade 0-1 acute dermatitis,and 8 cases (6.9％) and 6 cases (6.7％) with grade 2-3 respectively,with no statistically significant difference (x2 =0.004,P =0.948).There were 97 cases (83.6％) in HF-WBI group and 79 cases (87.8％) in CF-WBI group with grade 0-1 bone marrow suppression,and 19 cases (16.4％)and 11 cases (12.2％) with grade 2-4 respectively,with no statistically significant difference (x2 =0.704,P =0.401).In the two groups,there were 1 case (0.9％) and 3 cases (3.3％) with grade 1-2 radiation pneumonitis,and 115 cases (99.1％) and 87 cases (96.7％) with no radiation pneumonitis respectively,and the difference was not statistically significant (x2 =1.626,P =0.202).There was 1 case (0.9％,1.1％) with grade 1 breast edema in each group,and 115 cases (99.1％) and 89 cases (98.9％) did not occur breast edema,with no statistically significant difference (x2 =0.033,P =0.857).In the late adverse reactions,there were 5 cases (4.3％) and 3 cases (3.3％) with skin pigmentation in HF-WBI group and CF-WBI group respectively.There were 2 cases (1.7％,2.2％) with grade 1 subcutaneous tissue fibrosis in each group,and there were 1 case (0.8％) and 2 cases (2.2％) with grade 1 pulmonary fibrosis respectively.The differences between the two groups were not statistically significant (x2 =0.000,P ＞ 0.999;x2 =0.000,P ＞ 0.999;x2 =0.049,P =0.824).The 6-month,1-year and 2-year cosmetic outcome good rates in HF-WBI and CF-WBI group were 96.5％ (111/115) and 93.3％ (84/90),92.1％ (105/114) and 90.0％ (81/90),91.4％ (53/58) and 87.2％ (41/47) respectively.The differences between the two groups were not statistically significant (x2 =0.526,P =0.468;x2 =0.277,P =0.599;x2 =0.476,P =0.490).The whole course of radiotherapy time in HF-WBI group was 25 days or 29 days,which was significantly shorter than the 40 days of CF-WBI group.Conclusion HF-WBI after breast-conserving surgery has the similar long-term effect,acute and late adverse reaction and cosmetic outcome compared with CF-WBI,and the treatment time is significantly shorter.It can be further promoted as the optimal adjuvant radiotherapy for early-stage breast cancer after breast-conserving surgery.

N-methyladenosine (mA), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3' consensus sequence, but does not to one without. The ZFD thus serves as the target recognition domain, a structural feature previously shown for DNA methyltransferases, and cooperates with the MTDs of METTL3-METTL14 for catalysis. However, the interaction between the ZFD and the specific RNA is extremely weak, with the binding affinity at several hundred micromolar under physiological conditions. The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel β-sheet. Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface. As a division of labor, the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from β-sheet and zinc finger 2. Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded, which may permit the cooperation between the two domains during catalysis. Together, the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA mA modification.

Immunotherapy has become a new treatment for malignant tumors following surgery,radiotherapy,and chemotherapy.Tumor immunotherapy is a hot topic in basic medical research and clinical research,in which the study on checkpoint protein inhibitors has attracted more attention.The previous studies confirmed that blocking certain checkpoints,such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1),can exert immunomodulatory effects in solid tumor treatments.Immune checkpoint inhibitors have demonstrated good efficacy in recent years.The PD-1/programmed death ligand-1 (PD-L1) signaling pathway is one of the important pathways for tumor immune escape.PD-1/PD-L 1-targeted drugs can reactivate anti-tumor immunity and achieve good therapeutic effects in the treatment of various tumors.However,anti-PD-1/PD-L1 treatment has a certain adverse reaction rate,and the response rate of treatment needs to be improved.In this paper,the research progress of PD-1/PD-L1 signaling pathway and anti-PD-1/PD-L1 drugs in the treatment of solid tumors was summarized,such as malignant melanoma,lung cancer,renal cell carcinoma,gastrointestinal cancer,bladder cancer,etc.

Hypofractionated radiotherapy after breast conserving surgery has become a new standard treatment of early breast cancer. Clinical researches show that α/ β value of breast cancer is lower than that of other tumors,and the breast cancer is more suitable for hypofractionated radiotherapy. Hypofractionated radio-therapy has good economic benefits,and long-term follow-up results from a number of classical randomized con-trolled studies have shown that hypofractionated whole breast irradiation is effective and safe. With the extensive application of hypofractionated irradiation,this technology has been gradually extended to regional nodal irradia-tion,postmastectomy radiotherapy and breast ductal carcinoma in situ.

Objective To explore the zero cited fund papers in clinical nursing in China,in order to provide evidence for improving the academic quality and cite rate of nursing papers.Methods Bibliometric statistical analysis was used to summarize zero cited papers published in 12 nursing core journals from 2012 to 2014.Indicators collected including the distribution of time,journals,funding number,funding sources,research methods,research design type,statistics method,number of cooperative people,nature of the authors' organizations,as well as the conditions of cited papers and the distribution of themes.Results The overall zero cited rate of clinical nursing zero cited fund papers was 74.64％.Affiliated hospital of colleges account for a large proportion of 42.53％,and the zero cited rate in the national disease research center and the affiliated hospital of army colleges was the highest (100.00％ and 80.52％).The oncology nursing,disease and symptoms care proportion was 13.94％ and 23.10％.The output of TCM care and rehabilitation care fund paper accounted only 3 and 8 respectively,and none was cited.The zero cited rates of social support,care coordination,treatment and care attitude and evidence-based research were 96.3％,94.12％,91.67％,90.32％.Strengthened their awareness of research applications,managers focused on research papers in the number of outputs at the same time and paid attention to the paper quality,and promoted scientific research into nursing,and promoted the development of nursing discipline.Conclusions The current paper-citing situation in clinical nursing was not optimistic,nursing research personnel should correct the attitude of scientific research,strengthen their own sense of scientific achievement applications.The management personnel should pay more attention to the paper quality,and promote nursing research outcome transformation,promote the development of nursing discipline.

Objective: Laboratory-based characterization and traceability were performed on an outbreak of necrotising enterocolitis (NEC) happened in a maternal and child health care hospital in China. Methods: Thirty-seven samples were collected from 3 NEC cases, that the clinical manifestations was bloody stools. Clostridium spp. isolation and identification were carried out on stool, breast milk, milk-based infant powder and environmental swab samples collected during NEC outbreak from October to November in 2016. Meanwhile, twenty-four swabs samples from ward environmental, staffs' hand as well as articles for neonates daily use were also collected and tested for Clostridium spp. after disinfection following outbreak. Pulsed-field gel electrophoresis (PFGE) analysis was performed on all Clostridium strains obtained. Results: 46% (17/37) samples were positive for a presumptive Clostridium spp. during the outbreak of NEC. One type of Clostridium spp. isolates was cultured from 10 samples including the hands of medical staffs, some medical equipments in the ward and milk-based infant powder ingested by the case, it was identified as C.butyricum. Another type of Clostridium spp. isolates was cultured from 2 samples including breast milk and inner wall of breast milk fresh-keeping bag, it was identified as C.sporogens. Both of these two types isolates were cultured from 5 samples including inner wall of breast milk box, inner wall of refrigerator, the handle of case's incubator and the case's stool. PFGE analysis showed that all 15 strains of C. butyricum and 7 strains of C.sporogens isolated from the samples mentioned above produced indistinguishable pulsotypes respectively. No NEC cases were found after disinfection following the outbreak and all samples collected after outbreak were negative for Clostridium spp. Conclusion The outbreak of NEC was highly related to C. butyricum contamination within the hospital.

Objective: To analyses the antimicrobial resistance and molecular characterization of 21 MRSA isolates cultured from retail foods from different provinces in China, and evaluate the molecular typing methods. Methods: Twenty-one MRSA isolates were obtained from national foodborne pathogen surveillance network in 2012 (Chinese salad, n=3; milk, n=1; cake, n=2; rice, n=1; cold noodle, n=1; spiced beef, n=1; dumpling, n=1; packed meal, n=1; salad, n=1; raw pork, n=9). The antimicrobial resistance of 21 strains to 12 antimicrobial agents was tested by broth dilution method. Polymerase chain reaction (PCR) and DNA sequencing were performed to obtain the genetic types of MLST (ST) and spa typing. The clonal complex (CC) was assigned by eBURST soft and the MLVA type (MT) and MLVA complex (MC) were identified via the database of the MLVA website (http://www.mlva.net). SmaI pulsed-field gel electrophoresis (SmaⅠ-PFGE) was also carried out to obtain the PFGE patterns of 21 strains. The genetic diversity and discriminatory power of typing were calculated by the Simpson's index of diversity (diversity index, DI) to find out the best genotyping method for MRSA. Results: All MRSA isolates showed multi-drug resistance(MDR), and were resistant to oxacillin, benzylpenicillin, clindamycin and erythromycin, and 71.4% (15/21), 47.6% (10/21), 42.9% (9/21) and 28.6% (6/21) of the MRSA isolates were resistant to tetracycline, ciprofloxacin, trimethoprim/sulfamethoxazole and gentamicin, respectively. Moreover, one strain was found to be resistant to all three antimicrobials of levofloxacin, moxifloxacin and rifampicin. Great diversity was found in these food-associated MRSA (6 STs, 7 spa types, and 9 MTs). PFGE patterns were more diverse than those of other three molecular typing methods (19 pulse types). The index of diversity (DI) of PFGE, MLVA, spa typing and MLST was 0.99, 0.80, 0.73, and 0.61, respectively. Among the MRSA isolates, CC9-ST9-t899-MT929-MC2236 (PFGE Cluster Ⅴ) was the most prevalent clone, which were all cultured from raw pork (9 isolates). Besides, two MRSA were identified as CC59-ST338-t437-MT621-MC621 (PFGE Cluster Ⅳ). Different clone had their own resistance spectrum profiles. Conclusion The food-borne MRSA isolates were all MDR in this study. Different clones had their own resistance spectrum profiles. MLVA represented a promising tool for molecular epidemiology tracing of MRSA in foodborne disease events.