[Association between digestive tract cancer and severity of coronary artery disease].

Objective: To evaluate the association between digestive tract cancer and anatomical severity of coronary artery disease. Methods: This study enrolled 142 patients with digestive tract cancer who underwent coronary angiography in the Department of Cardiology of the First Medical Center of Chinese PLA General Hospital from 2009 to 2020 as the cancer group. The patients in cancer group were matched with 426 non-cancer patients who underwent coronary angiography at our hospital during the same period in a 1∶3 ratio based on gender and age. All enrolled patients had no previous history of percutaneous coronary intervention or coronary artery bypass grafting surgery. The severity of coronary artery disease was documented and assessed using the SYNTAX score based on angiogram. High SYNTAX score (SXhigh) was defined as SYNTAX score≥22 (upper quartile), while low SYNTAX score (SXlow) was SYNTAX score<22. High NLR (NLRhigh) was NLR≥2.287 (median), while low NLR (NLRlow) was NLR<2.287. The association between digestive tract cancer and severity of coronary artery disease was analyzed using logistic regression analysis. Results: This study included a total of 568 patients, with a mean age of (66.6±8.7) years. Among them, 430 patients (75.7%) were male. The cancer group consisted of 142 patients with digestive tract cancers, with a mean age of (66.5±8.4) years. The non-cancer group consisted of 426 patients, with a mean age of (66.7±8.8) years. The proportion of SXhigh in patients with digestive tract cancers (33.1%, 47 patients) was higher than that in non-cancer patients (23.9%, 102 patients) (P=0.032). Compared to non-cancer patients, SXhigh in patients with digestive tract cancers was higher (OR: 1.614, 95%CI: 1.051-2.481, P=0.029). Subgroup analysis stratified by NLR levels revealed that in the NLRhigh group, patients with digestive tract cancers exhibited a higher severity of coronary artery disease compared to non-cancer patients, with an OR of 1.948 (95%CI: 1.005-3.779, P=0.048). In the NLRlow group, there was no significant relationship between digestive tract cancers and the severity of coronary artery disease, with an OR of 1.277 (95%CI: 0.586-2.781, P=0.538). Conclusions: Digestive tract cancer is associated with the severity of coronary artery disease, and patients with digestive tract cancers have a higher risk of severe coronary artery disease than non-cancer patients. Additionally, there is an association between digestive tract cancers and the severity of coronary artery disease under conditions of high levels of inflammation.

[Performance of point-of-care testing for cervical cancer screening].

Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.

Probiotic supplementation containing Bacillus velezensis enhances expression of immune regulatory genes against pigeon circovirus in pigeons (Columba livia).

AIMS: In this study, we aimed to isolate and evaluate the efficacy of Bacillus velezensis as a probiotic and to assess its activity towards pigeons infected with pigeon circovirus (PiCV). METHODS AND RESULTS: Bacillus velezensis, isolated from pigeon faeces, was orally administered to pigeons for 60 days. After pigeons were challenged with PiCV, the PiCV viral load and expression of indicator genes for innate immunity were detected in spleen tissue and faeces of pigeons. Bacillus velezensis significantly reduced the PiCV viral load in the faeces and spleen of pigeons 5 days post-challenge (dpc). The mRNA expression levels of treated pigeons showed that interferon-gamma (IFN-γ), myxovirus resistance 1 (Mx1), and signal transducers and activators of transcription 1 (STAT1) genes were upregulated, whereas no expression of interleukin-4 (IL-4) was detected. Moreover, toll-like receptor 2 (TLR2) and 4 (TLR4) were significantly upregulated in probiotic-treated pigeons (P < 0·05). CONCLUSIONS: This is the first report showing that probiotic supplementation can effectively enhance the T-helper type 1 immune response and decrease the PiCV viral loads in pigeons. SIGNIFICANCE AND IMPACT OF THE STUDY: This study proposes that the administration of a probiotic strain, B. velezensis, to pigeons can protect against PiCV infection.

[Acceptance evaluation of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening].

Objective: To compare the acceptance of urine self-sampling, vaginal self-sampling and physician sampling in cervical cancer screening. Methods: Questionnaire surveys were conducted in women attending cervical cancer screening in Xiangyuan County and Yangcheng County in Shanxi Province from July to November 2015 and from October to December 2018. Both surveys included the following three parts: feelings and acceptance of women in urine self-sampling, vaginal self-sampling and physician sampling, and the ease evaluation of two self-samplings. Results: There were 3 485 questionnaires were collected finally. The proportions of women felt embarrassed in urine self-sampling, vaginal self-sampling and physician sampling were 2.3% (81/3 472), 7.1% (247/3 472) and 8.6% (299/3 472), and 1.3% (46/3 472), 9.7%(3 37/3 472) and 14.9% (518/3 472) of women felt uncomfortable, and 1.0% (35/3 469), 8.5% (295/3 469) and 15.3% (531/3 469) felt pain, and 98.3% (3 334/3 393), 96.3% (3 267/3 393) and 99.0% (3 360/3 393) thought that the sampling were conducted properly (P<0.05). Based on the feeling during sample collection, 61.2% (1 876/3 064), 39.1% (1 199/3 064) and 66.5% (2 037/3 064) women were willing to use the corresponded sampling methods in cervical cancer screening, respectively (P<0.05). If the accuracy was the same, there were 31.8% (1 109/3 485) women preferred self-sampling and 68.2% (2 376/3 485) preferred physician sampling for cervical cancer screening. Meanwhile, 23.5% (820/3 482) preferred vaginal self-sampling in comparison with 76.5% (2 662/3 482) for urine self-sampling in cervical cancer screening. 86.5% (3 007/3 478) of the women thought urine self-sampling was very easy, comparing 40.9% (1 423/3 478) for vaginal self-sampling. Conclusions: The bad feeling of women during urine self-sampling is less common and less serious than those during physician sampling and vaginal self-sampling, and the acceptance for physician sampling is highest, following by urine self-sampling and vaginal self-sampling. Urine self-sampling is much easier than vaginal self-sampling.

[Interpretation of "WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention， second edition"].

Cervical cancer can be eliminated through primary, secondary, and tertiary prevention. Yet it remains one of the gravest threats to women's lives worldwide. In November 2020, the World Health Organization (WHO) officially launched the global strategy to accelerate the elimination of cervical cancer, and underlined that screening and treatment for cervical pre-cancer lesions are two of three key measures for the elimination. In July 2021, WHO issued the second edition of"WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention"to provide important guidance to countries to support them in achieving the target of cervical cancer elimination in all women. This article will interpret the methods for the guideline development, the recommendations/good practice statements on screening and treatment to prevent cervical cancer (including the age to start/stop screening, screening methods, screening interval, the management of screen-positive women and treatment of the precancerous lesions, etc.) and its impact globally, providing reference for the updates of guideline and policy making on cervical cancer prevention and control in China.

[Global development of human papillomavirus vaccination guidelines: a systematic review].

Objective: To systematically summarize the development of global human papillomavirus (HPV) vaccination guidelines. Methods: The retrieval for all the Chinese and English literature published before August 2020 was conducted in PubMed, Embase and China Biomedical Literature Database, with "papillomavirus vaccines" "wart virus vaccine" "guideline" "practice guideline" "health planning guidelines" "guidelines as topic" "practice guidelines as topic" "immunization programs" in English as well as "papillomavirus vaccines" "HPV vaccine" "guideline" "recommendation" "consensus" in Chinese as search keywords. A total of 18 guidelines were included for data extraction and analysis. Results: The 18 pieces of guidelines included 1 pieces of World Health Organization (WHO) position paper, 6 pieces of guidelines at national or provincial level and other 11 pieces of by academic institutions. In national or provincial guidelines, the recommendation for routine vaccination mainly focused on 11-13 year-old adolescents and the recommendation for catch-up vaccination extends to 17-26 years old. Recommendation of guidelines by academic institutions were similar to the WHO position paper: girls aged 9-14 as the primary target for the routine vaccination; females aged 15-26 years old as the secondary target populations when it's feasible, affordable and cost-effective; women aged over 26 could be vaccinated at an individual level. There were only three guidelines simultaneously updated with the national immunization programme and covered four aspects: the vaccinated population (girls-only to gender-neutral vaccination), the periodic catch-up immunization, the dose schedule updates and the change of vaccine types. Conclusions: It's recommended that the development of Chinese HPV vaccination guidelines refer to global guidelines and updates and take full consideration of the epidemiological evidence, resources and current status of the immunization system in China.

[Analysis of the clinical efficacy and safety of bronchial thermoplasty in the treatment of patients with severe asthma and asthma-chronic obstructive pulmonary disease overlap].

Objective: To investigate the clinical efficacy and safety analysis of bronchial thermoplasty (BT) in the treatment of severe asthma and asthma-chronic obstructive pulmonary disease overlap. Methods: The clinical data of 49 patients with asthma-COPD overlap who received BT in the University of Chinese Academy of Sciences Shenzhen Hospital from January 2016 to December 2018 and 50 patients with severe asthma who received BT in the same period were retrospectively analyzed. Patients were divided into overlap group and asthma group, and the baseline data of two groups were recorded. The pulmonary function before and after treatment (including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1 as a percentage of predicted value (FEV1% pred)), hormone consumption, asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score, asthma control questionnaire (ACQ) score, the overlap group before and after treatment COPD assessment test (CAT) score, modified British Medical Research Council (mMRC) score and postoperative respiratory adverse events in the next 3 weeks were comparatively analyzed. Results: The general baseline characteristics of the two groups are compared. The patients in the overlap group were older than those in the asthma group, and the course of disease and smoking history were longer than those in the asthma group. The inhaled hormone dosage in asthma group was greater than those in the overlap group ((64±11) years vs (48±11) years; 10.00 (10.00, 25.00) years vs 9.00 (1.75, 20.00) years; 20.00(2.00, 40.00) years vs 0 (0, 10.00) years; 320 (320, 640) µg/d vs 960 (320, 960) µg/d) (all P<0.05). The predicted values of lung function indexes FVC, FEV1, FEV1% pred in the overlap group before treatment were all lower than those in the asthma group (1.98 (1.43, 2.43) L vs 2.54 (2.02, 3.15) L; 0.92 (0.61, 1.26) L vs 1.69(1.17, 2.16) L; (50±16) L vs (65±14) L) (all P<0.05). There were no significant differences in ACT, ACQ, and AQLQ scores between the two groups before treatment (all P>0.05). Within 3 months after treatment, except for no significant improvement in FEV1% predicted value and inhaled hormone dosage in the overlap group (all P>0.05), other indexes in both groups were improved compared with those before treatment (all P<0.05). After 1 year of treatment, all indexes of the two groups were significantly improved than those before treatment, and all indexes of the asthma group were better than those of the overlap group (all P<0.05). In terms of respiratory adverse events occurring within 3 weeks after the operation, the incidence of cough and bloody sputum in the overlap group was higher than that in the asthma group, while the incidence of sputum and short-term wheezing was lower than that in the asthma group (all P<0.05). There were no statistically significant differences in the incidence of chest tightness, chest pain, segmental atelectasis and pneumonia between the two groups (all P>0.05), and the postoperative adverse reactions could be effectively controlled in a short period of time. Conclusion: BT treatment could not only improve the lung function, clinical symptoms and quality of life of asthmatic patients, but was also effective for asthma-COPD overlap patients. However, BT treatment had more benefits for asthmatic patients without serious adverse events occurred.

[Effectiveness of the thermal ablation in the treatment of human papillomavirus infection and cervical intraepithelial neoplasia in Chinese women].

Objective: To evaluate the effectiveness of thermal ablation in the treatment of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in Chinese women. Methods: The high-risk HPV-positive women aged 20-65 who were detected through a cervical cancer screening project implemented in three rural sites (Etuoke counties in Inner Mongolia, Xiangyuan and Yangcheng counties in Shanxi Province) and one urban site (Shenzhen) in China were included in this prospective study. Follow up evaluation was performed on HPV positive women who underwent thermal ablation (n=166) as well as received no treatment (n=2 716) in cervical cancer screening program. For women with thermal ablation treatment, HPV test and cytology were used for follow-up with the interval of 6 months or longer after treatment. For women without treatment, HPV test was used for annual follow-up. Women with positive results in either of the HPV tests or abnormal cytology were referred for a colposcopy or biopsy if necessary. The HPV clearance rate and the cure rate of CIN were compared between the two groups. Results: A total of 152 women treated with thermal ablation and 2 539 women without treatment reported for follow-up evaluation with the age M(Q1, Q3) of 42 (36, 48) and 47 (41, 54) years old, and the median time to follow-up time of 23.4 (12.4, 24.5) and 23.5 (12.4, 24.0)months, respectively. The HPV clearance rate in women undergoing thermal ablation was significantly higher than that in women with no treatment (73.0% vs 46.1%, P<0.001). The HPV16, HPV52 and HPV58 clearance rates among women receiving thermal ablation were higher than that in women without treatment with the OR (95%CI) of 2.8 (1.3-6.1), 3.2 (1.3-7.9) and 5.8 (2.1-15.6). For women with histologically confirmed CIN at baseline, cure rates were 77.4%(n=72) for thermal ablation. Cure rates of the thermal ablation were 81.0%(n=47) for CIN grade one (CIN1) and 71.4% (n=25) for CIN grade two or worse (CIN2+). Conclusions: Thermal ablation is effective to clear the HPV infection as well as to treat CIN. Particularly for the HPV genotypes with the paramount attributable proportion to cervical cancer and precancerous in China, the HPV clearance rate was significantly higher than that reported in the women without treatment.

[Analysis of the safety and efficacy of bronchial thermoplasty for severe asthma with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred)<60].

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in severe asthma patients with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred) <60%. Methods: A retrospective analysis was performed on 75 patients with asthma who were treated with BT at Shenzhen University Hospital of the Chinese Academy of Sciences from January 2016 to January 2018. The patients were divided into two groups based on the FEV(1)%pred before treatment: FEV(1)%pred <60% group (39 cases) and FEV(1)%pred ≥60% group (36 cases). Comparative analysis of glucocorticoid consumption, times of acute attack, asthma control test (ACT) score, changes in lung function, and adverse reactions at 3 weeks after treatment were performed between the two groups of patients. Results: Before BT treatment, the consumption of oral prednisone, the amount of budesonide inhaled, and the times of acute attack [M (Q(1), Q(3))] in the FEV(1)%pred <60% group were significantly greater than those in the FEV(1)%pred ≥60% group, and the ACT score was significantly lower than the FEV(1)%pred ≥60% group [10.00 (0, 20.00) vs 0(0, 3.75) mg/d, 960 (320, 960) vs 320 (320, 640) µg/d, 5(4, 8) vs 4 (4, 5) times/year, 13 (9, 15) vs 17 (13, 19) scores] (all P<0.05). Except that the oral prednisone dosage in the FEV(1)%pred<60% group was still higher 1 year after treatment [0 (0, 5.00) vs 0 (0, 0) mg/d] (P=0.009), there was no significant difference in the remaining indicators between the two groups 1 year after treatment and 2 years after treatment (all P>0.05). After 1 year and 2 years of treatment, all indicators in the two groups were better than before treatment (all P<0.05). The inhaled budesonide amount and the times of acute exacerbation in the FEV(1)%pred <60% group 2 years after treatment were less than those 1 year after treatment [320 (320, 320) vs 320 (320, 640) µg/d, 0 (0, 0) vs 0(0, 1) times/year] (all P<0.05), and there was no significant difference in the remaining indicators. In the FEV(1)%pred ≥60% group, there was no significant difference between 2 years after treatment and 1 year after treatment in the above indicators except the amount of inhaled budesonide (all P>0.05). In the FEV(1)%pred <60% group, FEV(1) and the FEV(1)%pred were significantly lower than the FEV(1)%pred ≥60% group before treatment, 1 year after treatment and 2 years after treatment [FEV(1):(1.21±0.41) vs (2.26±0.80)L, (1.84±0.73) vs (2.30±0.78)L, (1.70±0.66) vs (2.38±0.76)L; FEV(1)%pred:46.2 (38.5, 53.7)% vs 80.8(66.5, 93.6)%, 60.1 (48.2, 71.6)% vs 87.4 (68.5, 96.5)%, 58.5 (48.6, 74.8)% vs 86.6 (73.0, 97.3)%] (all P<0.05). In the FEV(1)%pred <60% group, FEV(1) and FEV(1)%pred 1 year after treatment and 2 years after treatment were all increased compared with before treatment (all P<0.05). In the FEV(1)%pred ≥60% group, there was no statistical difference in FEV(1) at each time point before and after treatment (all P>0.05), but the FEV(1)%pred at 2 years after treatment was higher than before treatment (P<0.05). There were no significant differences in adverse events between the two groups (all P>0.05). Conclusion: BT can significantly improve the lung function, reduce the times of acute attack and the dosage of glucocorticoids in severe asthma patients with FEV(1)% pred<60%, which is safe and effective.

[Preliminary application of postoperative fast track transfer to intensive care unit for the geriatric hip fractures under enhanced recovery after surgery].

Objective: To develop a fast track transfer to intensive care unit (ICU) for the perioperative high-risk elderly patients after hip fracture surgery and analyze the preliminary clinical effect of the application. Methods: From January 2014 to December 2017, before the application of postoperative fast track transfer to ICU, the clinical data of 195 elderly patients with hip fracture were included in a retrospective analysis. Among 195 hip fracture patients, 18 were transferred to ICU post operation (non-fast track group). Multivariate logistic regression analysis was applied to investigate relevant risk factors for transferring to ICU after hip fracture surgery. Based on risk factors acquired from the analysis and clinical experience, the fast track transfer to ICU for the perioperative high-risk elderly patients after hip fracture surgery was constructed according to the preliminary and experiential criteria. From January 2018 to December 2019, the clinical data of 70 patients (fast track group) who were transferred to ICU after hip fracture surgery through the fast track were collected and compared with non-fast track group. Results: Multivariate regression analysis revealed that American Society of Anesthesiologists classification(≥Ⅲ) (OR=4.260, 95%CI:1.157-15.683, P=0.029), pre-hospital stage (≥48 h) (OR=4.301, 95%CI:1.212-15.266, P=0.024), hemoglobin concentration at admission(<90 g/L) (OR=7.979, 95%CI:1.936-32.889, P=0.004), coronary heart disease as one comorbidity(OR=6.063, 95%CI:1.695-21.693, P=0.006) were independent risk factors for transferring to ICU after hip fracture surgery. There were no significant difference in gender, age, fracture type, hemoglobin concentration at admission and time of pre-hospital stage between the non-fast track group and fast track group(all P>0.05). However, the number of comorbidities in the fast track group was significantly higher than that in the non-fast track group (Z=-1.995, P=0.046). The time to surgery, postoperative hospital stay, and length of hospital stay in fast track group were all significantly less than those in non-fast track group (Z=-2.121, -2.726, -3.130, all P<0.05). Also, there were fewer medical consultations needed and fewer patients who stayed in ICU more than or equal to 2 nights in fast track group than that in non-fast track group(all P<0.05). There were no significant difference in the rate of patients who transferred from the general ward to ICU after transferring from ICU to the general ward, the proportion of patients who received more than or equal to 4 departments, operation time, hospitalization expense, mortality during hospitalization, 30-day mortality and 90-day mortality after operation between the two groups(all P>0.05). Conclusions: The fast track constructed in this study can reduce time to surgery, postoperative hospitalization stay and length of hospitalization stay for the perioperative high-risk elderly patients with hip fractures and is a specific clinical application of eras concept based on multidisciplinary team.

[Value of intravoxel incoherent motion diffusion weighted imaging in evaluating the microstructure changes in white matter hyperintensities].

Objective: To investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM DWI) in evaluating microstructure changes in elderly white matter hyperintensities (WMH) patients and to analyze the correlation between IVIM parameters and severity grading and cognitive scores. Methods: Sixty-two WMH patients in Zhejiang Hospital were collected from December 2014 to March 2018 and underwent conventional magnetic resonance (MR) plain scan and diffusion weighted imaging with different b values. The age was 60-92(74±10) years with 37 males, 25 females. The severity of WMH was assessed by T(2) fluid attenuated inversion recovery (FLAIR) sequence and Fazekas score,which were divided into two subgroups. Slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) from IVIM parameters of double exponential model were compared between regions of WMH (deep WMH (DWMH) and periventricular WMH (PWMH)) and surrounding normal white matter (NWM).The Shapiro-Wilk test was used for normality tests, Kruskal-Wallis tests and Dwass-Steel-Critchlow-Fligner (DSCF) procedure were used for the comparison among these parameters. Furthermore, Wilcoxon two-sample test was used for the comparisons between different severity. Pearson correlation analysis was performed to determine whether these D, D(*), f values were correlated with the mini mental state examination (MMSE) scores. Results: D(D)WMH (0.83(0.72,0.99)×10(-3) mm(2)/s), D(PWMH)((1.13±0.25)×10(-3) mm(2)/s) were significantly higher than D(NWM) ((0.71±0.05)×10(-3) mm(2)/s)(P<0.01). f (DWMH) ((8.94%(7.46%,11.67%)), f (PWMH)(8.34%(6.73%,9.96%)) were significantly higher than f (NWM)(6.71%±1.72%)(P<0.01).D in DWMH were significantly lower than that in PWMH(P<0.01), there's no statistically difference between other groups. D in severe WMH (both DWMH and PWMH) were significantly higher than that in mild WMH (P=0.000 1, P=0.04). Only f in PWMH were positively associated with the MMSE scores (r=0.326 5,P<0.05). Conclusions: IVIM DWI can noninvasively assess the variation of microstructure diffusion and perfusion in WMH in one sequence,which may objectively reflect the severity of these lesions. This method has important clinical significance for better assessment and management of this disease.

[Multi-channel promotion of lung cancer progress by bone marrow derived mesenchymal stem cells in tumor microenvironment].

Objective: To observe the growth and metastasis of lung cancer promoted by bone marrow derived mesenchymal stem cells (BMSCs) in tumor microenvironment and investigate the underlined mechanisms. Methods: Specific chemotaxis of BMSCs towards lung cancer was observed, and the tumor growth and metastasis were assessed in vivo. Furthermore, CD34 expression determined by immunohistochemistry was used to assess the microvessel density (MVD), and the expressions of GFP and α-SMA determined by immunofluorescence were used to detect the BMSCs derived mesenchymal cells. We investigated the effect of BMSCs on migration, invasion of lung cancer cells including A549 and H446 cells by using scratch assays and Transwell Assay in vitro. We also explored the effect of BMSCs on epithelial mesenchymal transition of A549 and H446 cells by observing the phenotype transition and E-Cadherin protein expression detected by Western blot. At last, we screened the potentially key soluble factors by enzyme linked immunosorbent assay (ELISA). Results: In NOD mice, labeled BMSCs injected via tail vein were special chemotaxis to tumor cells, and promoted the tumor growth [the time of tumor formation in A549+ BMSCs and A549 alone was (5.0±1.5) days and (10.0±3.6) days, respectively, P<0.05; the time of tumor formation in H446+ BMSCs and H446 alone was (5.2±1.5) days and (12.0±2.0) days, respectively, P<0.05]. The tumor incidence of A549+ BMSCs was 100%, significantly higher than 66.7% of A549 alone (P<0.05), while the tumor incidence of H446+ BMSCs was 83.0%, significantly higher than 50.0% of H446 alone (P<0.05). The BMSCs also increased the tumor volume [the tumor volume of A549+ BMSCs and A549 alone was (193.0±42.3) mm(3) and (97.8±42.9) mm(3,) respectively, P<0.05; the tumor volume of H446+ BMSCs and H446 alone was (78.6±34.8) mm(3) and (25.3±12.7) mm(3,) respectively, P<0.05] and facilitated the tumor metastasis (the tumor metastatic incidence of A549+ BMSCs and A549 alone was 100.0% and 16.7%, respectively, P<0.05; the tumor metastatic incidence of H446+ BMSCs and H446 alone was 100.0% and 0.0%, respectively, P<0.05). Furthermore, BMSCs increased tumor vessel formation (the MVD of A549+ BMSCs and A549 alone was 53.2±11.4 and 25.3±11.5, respectively, P<0.05; the MVD of H446+ BMSCs and H446 alone was 56.8±12.5 and 24.8±10.0, respectively, P<0.05). BMSCs were able to differentiate to fibroblasts in the lung squamous cell carcinoma and promoted the migration and invasion of lung cancer cells (the A of cells in the migrated lower chambers of A549+ BMSCs and A549 alone was 1.9±0.2 and 1.1±0.1, respectively, P<0.05; the A of cells in the migrated lower chambers of H446+ BMSCs and H446 alone was 1.9±0.3 and 0.9±0.2, respectively, P<0.05). The cell shape was longer and sharper, the intercellular junctions were reduced and the relative expression level of E-Cadherin protein in A549 co-cultured with BMDCs was 0.36, significantly down-regulated when compared to 0.55 of A549 alone (P<0.05), and the relative expression level of E-Cadherin protein in H446 co-cultured with BMDCs was 0.28, significantly down-regulated when compared to 0.46 of H446 cells alone (P<0.05). The concentration of IL-6 in the conditional medium of BMSCs, A549 co-cultured with BMSCs and H446 co-cultured with BMSCs was 910.5, 957.2, and 963.8, respectively, significantly up-regulated when compared to 18.8 of control group (P<0.05). The expression level of PGE2 in A549 co-cultured with BMSCs and H446 co-cultured with BMSCs was 130.5 and 87.2, significantly up-regulated when compared to 13.8 of control group and 23.8 of BMSCs group (P<0.05). Conclusions: Our results suggest that BMSCs contribute to the tumor growth through facilitating angiogenesis, and promote tumor metastasis through paracrine manner and down-regulation of E-Cadherin protein. IL-6 and PGE2 produced by BMDCs might be the potentially important cytokines.

[Risk stratification of type-specific human papillomavirus for cervical precancers: evidence from a cross-sectional study in Shenzhen].

Objective: To analyze the epidemiological genotype features of human papillomavirus (HPV) in cervical infection and their risks for cervical precancers among women in Shenzhen area. Methods: A total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology (LBC), colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia (CIN) 2 and above were estimated. Results: The HPV infection rate in Shenzhen area was 15.9% (432/2 717). The most common HPV genotype was HPV52 (22.9%), followed by HPV16 (12.7%), HPV53 (10.0%), HPV51 (8.6%) and HPV58 (8.1%). Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity (57.1% vs. 42.9%, P<0.05) and an analogous specificity (87.3% vs. 86.9%, P>0.05) in predicting CIN2+ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion (LSIL) positive tested by LBC in predicting CIN2+ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance (ASC-US) positive tested by LBC alone (P<0.05). The specificities of these two methods mentioned above in predicting CIN2+ were 83.5% and 89.2%, respectively, without statistical difference (P>0.05). Conclusions: Women infected by HPV have distinct risks for CIN2+ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL+ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.

[The safety of decitabine as bridging pretreatment regimen before hematopoietic stem cell transplantation in pediatric hematological malignancies].

The safety of decitabine as bridging treatment before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with refractory hematological malignancies was evaluated. All 11 cases succeeded in hematopoietic reconstitution. The main adverse reaction was hematological toxicity. Neither did infections occur, nor drug-induced liver damage and renal impairment during decitabine administration. Most cases showed grade Ⅰ-Ⅱgastrointestinal adverse events. One case was diagnosed as severe acute graft versus host disease and died of intracranial hemorrhage on day 61 after allo-HSCT. The other 10 patients survived. Decitabine bridge is a safe regimen before allo-HSCT in children with refractory hematological malignancies.

[Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions].

Objective: To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+). Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups. Results: Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ(2)=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ(2)=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ(2)=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting. Conclusion: Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

[Role of HPV viral loads in random biopsy under normal colposcopy].

Objective: To explore the role of HPV viral loads in random biopsy under normal colposcopy. Methods: 908 atypical squamous cells of undetermined significance (ASC-US) and HPV positive women, recruited in cluster sampling in 9 provinces including 5 urban areas and 9 rural areas in China from 1999 to 2008 and meeting the inclusion and exclusion criteria were included in this analysis. According to relative light units/cutoff (RLU/CO) value, subjects were stratified as low (286 cases), intermediate (311 cases) and high (311 cases) viral load groups. Risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among different viral load groups were compared with linear trend Chi-square test. Results: Detection rate of CIN3+ in low, intermediate and high viral load groups were 2.1% (6 cases), 2.6% (8 cases) and 6.8% (21 cases) (Chi-square test for trend χ(2)=8.91, P=0.003) and were 60.3, 74.0 and 201.3 times higher than ASC-US and HPV negative women, respectively. Among 908 subjects, 27.0% (245 cases) were abnormal under colposcopy and 68.6% (623 cases) diagnosed as normal. Under normal colposcopy, detection rate of CIN3+ in low, intermediate and high viral load groups were 0.9% (2 cases), 0.9% (2 cases) and 3.8% (7 cases) (χ(2)=6.42, P=0.040). Conclusion: HPV viral loads display satisfactory risk stratification ability among ASC-US and HPV positive women under normal colposcopy. Women with high HPV viral loads show a significantly increased detection rate of existing CIN3+ and could be recommended to perform random biopsy for histologic diagnosis.

[Distribution and associated factors of high-risk HPV genotypes infection among HPV-positive women who participated cervical screening test in Shenzhen, 2014-2016, China].

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ(2)=54.79, P<0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95%CI) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection (OR (95%CI): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 (OR (95%CI): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion: Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

[Chorionic villus cell culture and karyotype analysis in 1 983 cases of spontaneous miscarriage].

Objective: To investigate the relationship between spontaneous miscarriage and embryonic chromosome abnormalities, and to evaluate the clinical application of karyotype analysis by chorionic villus cell culture. Methods: The chorionic villus karyotype of 1 983 cases of miscarriage from January 2010 to July 2016 in Guangzhou Women and Children's Mecical Center were analyzed retrospectively. The miscarried chorionic villi were obtained by curettage under sterilized condition. The chromosome specimens were prepared after chorionic villus cell culture. Karyotype analysis was performed by G-banding technique. Results: In the 1 983 samples, successful karyotype analysis was performed in 1 770 cases, with the successful rate of 89.98%. Chromosomal abnormalities were found in 1 038 cases (58.64%, 1 038/1 770). Chromosomal structural abnormalities were found in 37 cases. The numeral abnormalities were more common than structural abnormalities, and most of the numeral abnormalities were aneupoidies. In turn, they were trisomy 16, 45,X, trisomy 22, trisomy 2, trisomy 21, trisomy 15. The most common structural abnormality was balanced translocation, including Robersonian translocation. Female embryoes accounted for 61.02% (1 080/1 770) miscarriages and for 57.4%(596/1 770) of chromosomal abnormalities, while male embroyes acoounted for 61.02% (1 080/1 770) , 57.4% (596/1 770) respectively. The proportion of female embryoes was higher than male embryoes. The median age of the patients was 30 years old (16-46 years old) . As the maternal age increased, the proportion chromosomal abnormalities increased. The incidence of chromosomal abnormalities in the advanced age group (≥35 years) was 68.38% (240/351) , which was significantly higher than that in the younger group (56.24%, 798/1 419; χ(2)=17.10, P<0.01). Conclusions: Embryonic chromosomal abnormalities are the most common cause of early spontaneous miscarriage. The abnormalities centralize in some karyotypes. There is certain relationship between maternal age and the incidence of miscarriage, as well as the embryonic gender. Chorionic villus cell culture and karyotype analysis are helpful in finding the cause of miscarriage and counsel the patients.

Low miR-29c expression is a prognostic marker in hepatocellular carcinoma.

A previous study has revealed that miR-29c functions as a tumor suppressor in hepatocellular carcinoma (HCC), but the clinical significance and prognostic value of miR-29c in HCC have not been investigated. Paired human HCC tissues and adjacent noncancerous tissues were obtained from 91 patients, between 2008 to 2014. Quantitative real-time PCR (qRT-PCR) was used to analyze miR-29c expression. Kaplan-Meier survival plots and log-rank tests were used to assess differences in the overall survival of different subgroups of HCC patients. It was observed that miR-29c expression was remarkably decreased in HCC tissues relative to that in normal hepatic tissues (P < 0.001). The low miR-29c level was significantly associated with histologic grade (P = 0.001), microvascular invasion (P = 0.005), and tumor stage (P < 0.001). Kaplan-Meier analysis showed that decreased miR-29c expression correlated with shorter overall survival (P = 0.002). Multivariate Cox regression analysis showed that decreased miR-29c expression (hazard ratio = 2.19, 95%CI = 1.361-6.779, P = 0.025) was independently associated with poor survival in HCC. Our findings demonstrate that miR-29c expression is significantly downregulated in HCC patients and that miR-29c can act as an independent predictor of unfavorable clinical outcome.

[Prevalence of human papillomavirus infection and risk of cervical cancer or precancerous lesions in 15 years follow up: a prospective cohort study].

Objective: To evaluate the 15 years changing trends of prevalence of high risk HPV (HR-HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+ ) among a Chinese rural population. Methods: The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province (SPOCCS-I) and followed up by cytology and HR-HPV testing in the years of 2005, 2010, and 2014. The changes of HR-HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results: The detection rates of HPV infection and CIN2+ were 15.7%-22.3% and 1.1%-4.3% for the baseline visit and the other 3 follow-ups, respectively. The cumulative risk of CIN2+ in HR-HPV positive women at baseline was significantly higher than HR-HPV negative women (P<0.01) during the 15-year follow-up. The risk of CIN2+ in the four-times HPV positive group was 40.0%, while the group with four-times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions: The prevalence of HR-HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR-HPV positivity elevated the risk of CIN2+ compared to women whose HR-HPV test was negative. The risks of CIN2+ incidence in 6 years were low among women with negative HR-HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5-6 years.