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Metabolic syndrome (MS) is common among obese people. Little is known about the magnitude and characteristics of MS in people living with HIV (PLWH) in Asian countries in general and China in particular. Using baseline data collected between February 2017 through January 2020 from the Comparative HIV and Aging Research in Taizhou (CHART) cohort in China, we examined MS among 2,227 PLWH and 5,264 matched people without HIV, respectively. MS was defined using the criteria set forth by the International Diabetes Federation (IDF). Approximately 76.7% of PLWH had body mass index (BMI) < 24.0 kg/m2, significantly higher than people without HIV (50.3%). Among participants with BMI < 24.0 kg/m2, PLWH had a significantly higher prevalence of MS than people without HIV (20.6% vs. 14.5%; aOR: 1.41, 95% CI: 1.19-1.68) overall, and at an age of 18-29 (10.4% vs. 3.4%, aOR: 3.49, 95% CI: 1.99-6.11) and 30-44 years (17.3% vs. 8.5%, aOR: 2.03, 95% CI: 1.47-2.81), respectively. Among participants with BMI ≥ 24.0 kg/m2, MS prevalence was not significantly different between PLWH and people without HIV overall, but significantly lower in PLWH than people without HIV for those aged over 60 years (65.9% vs. 77.8%, aOR: 0.53, 95% CI: 0.32-0.88). Among PLWH, MS was significantly associated with older age and higher CD4 cell count, and with stavudine (d4T) use only in the group of BMI < 24.0 kg/m2. Our finding is indicative of a relatively higher risk for early onset of MS among HIV-infected young adults with lower BMI. Research is needed to elucidate the pathogenic mechanism for MS among PLWH.

Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Adjuvant chemotherapy is usually used for distant control. However, not all patients can benefit from adjuvant chemotherapy, and particularly, some patients may even get worse outcomes after the treatment. We develop and validate an MRI-based radiomic signature (RS) for prediction of DM within a multicenter dataset. The RS is proved to be an independent prognostic factor as it not only demonstrates good accuracy for discriminating patients into high and low risk of DM in all the four cohorts, but also outperforms clinical models. Within the stratified analysis, good chemotherapy efficacy is observed for patients with pN2 disease and low RS, whereas poor chemotherapy efficacy is detected in patients with pT1–2 or pN0 disease and high RS. The RS may help individualized treatment planning to select patients who may benefit from adjuvant chemotherapy for distant control., Distant metastasis (DM) is the main cause of treatment failure in locally advanced rectal cancer. Here, the authors developed and validated a radiomic signature (RS) for prediction of DM within a multicenter dataset, and suggest that it may help with stratification of patients who might benefit from adjuvant chemotherapy for DM.

Objectives To report the cost-effectiveness of Xpert in detecting Mycobacterium tuberculosis (MTB) through a comprehensive systematic review. Methods Specialized bibliographic databases were searched. Study quality was evaluated by commonly-used industry standards. Due to heterogeneity, evidences were synthesized narratively. Results Four studies from intermediate-to-low tuberculosis (TB)-burdern areas and 17 studies from high-TB-burden areas were included. Smear microscopy, clinical diagnosis and chest radiography were mostly used for comparison. Cost elements varied considerably depending on the perspectives. Cost-effectiveness and cost-utility analyses were used by seven and fourteen studies, respectively. All studies were of high quality (CHEERS score of 78.4 and QHES score of 86.9). Average cost per test was 29.8 US$ for Xpert compared with 3.83 US$ for smear microscopy. Cost-effectiveness analyses mostly supported application of Xpert into areas under varying TB burdens. Conclusions Xpert seems cost-effective under respective willingness-to-pay thresholds in nations with differences in socioeconomy, HIV stress and geographical distribution. Nevertheless, policymakers will benefit from localized studies since regional economic/financial statuses and health-care system should also be considered apart from the reports of cost-effectiveness.

People living with HIV (PLWH) have an excess risk of cardiovascular diseases (CVD). Electrocardiographic (ECG) abnormalities are independently predictive of incident cardiovascular events in the general population. Our study aimed to evaluate the prevalence and correlates of ECG abnormalities among PLWH in Shanghai, China. We used a cross-sectional design to collect data from Shanghai Public Health Clinical Center, China. A total of 587 HIV-infected patients aged between 18 and 75 years were recruited between January 2015 and February 2016. The overall prevalence of any type of ECG abnormalities was 53.3%. The prevalence of sinus tachycardia, ST-T segment elevation and left ventricular hypertrophy was 23.0%, 18.1%, and 6.8%, respectively. Multivariable logistic regression analysis indicated that ST-T segment elevation was positively associated with higher baseline HIV viral load (≥ 4 log10 copies/mL), and sinus tachycardia was negatively associated with older age but positively associated with lower CD4 cell count, higher baseline HIV viral load (≥ 4 log10 copies/mL) and higher lactic dehydrogenase (LDH) level (≥133 mg/dL). Any coded ECG abnormality was positively associated with higher baseline HIV viral load (≥ 4 log10 copies/mL). ECG abnormalities including sinus tachycardia and ST-T segment elevation are prevalent among Chinese HIV patients, which are significantly associated with immunodeficiency and HIV viral load. Routine ECG screening may be an important part of HIV clinical care in China.

Anti-tuberculosis drug induced hepatotoxicity is the main problem in tuberculosis patients. Xanthohumol, a major prenyl chalcone present in hops, has diverse biological activities including antibacterial and hepatoprotective activities. The present research aimed to investigate the combined effect of xanthohumol with isoniazid against Mycobacterium tuberculosis-infected mice. The liver damage was induced by treatment with isoniazid daily for 8 weeks. During the experiment, the uninfected group and the normal control group received an equal volume of saline, the xanthohumol group received an equal volume of xanthohumol only, and the isoniazid group received an equal volume of isoniazid only. The combination therapy group received not only isoniazid but also the corresponding xanthohumol. Experimental results showed that isoniazid combined with xanthohumol resulted in the lowest lung and spleen colony-forming unit counts compared to other groups. Furthermore, other positive outcomes implied that isoniazid combined with xanthohumol obviously alleviated anti-tuberculosis drug induced liver damage as indicated by the declined levels of ALT, AST, ALP, bilirubin and MDA and the increased levels of SOD, GSH-Px and ATPases. The study of the mechanisms underlying the hepatoprotective activity showed that xanthohumol was able to activate the antioxidative defense system and protect the hepatocellular membrane. The combination of isoniazid and xanthohumol had more effective bacteriostatic and hepatoprotective activities on Mycobacterium tuberculosis-infected mice than isoniazid alone. In conclusion, xanthohumol has the potential to be an effective adjuvant in tuberculosis treatment.

Purpose This study aimed to develop and validate a nomogram for predicting the malignancy of small (8-20 mm) solid indeterminate solitary pulmonary nodules (SPNs) in a Chinese population by using routine clinical and computed tomography data. Methods The prediction model was developed using a retrospective cohort that comprised 493 consecutive patients with small indeterminate SPNs who were treated between December 2012 and December 2016. The model was independently validated using a second retrospective cohort comprising 216 consecutive patients treated between January 2017 and May 2018. The investigated variables included patient characteristics (e.g., age and smoking history), nodule parameters (e.g., marginal spiculation and significant enhancement), and tumor biomarker levels (e.g., carcinoembryonic antigen). A prediction model was developed by using multivariable logistic regression analysis, and the model's performance was presented as a nomogram. The model was evaluated based on its discriminative ability, calibration, and clinical usefulness. Results The developed nomogram was ultimately based on age, marginal spiculation, significant enhancement, and pleural indentation. The Harrell concordance index values were 0.869 in the training cohort (95% confidence interval: 0.837-0.901) and 0.847 in the validation cohort (95% confidence interval: 0.792-0.902). The Hosmer-Lemeshow test revealed good calibration in each of the training and validation cohorts. Decision curve analysis confirmed that the nomogram was clinically useful (risk threshold from 0.10 to 0.85). Conclusion Patient age, marginal spiculation, significant enhancement, and pleural indentation are independent predictors of malignancy in small indeterminate solid SPNs. The developed nomogram is easy-to-use and may allow the accurate prediction of malignancy in small indeterminate solid SPNs among Chinese patients.

ObjectivesTo evaluate the value of synthetic magnetic resonance imaging (syMRI), diffusion-weighted imaging (DWI), DCE-MRI, and clinical features in breast imaging–reporting and data system (BI-RADS) 4 lesions, and develop an efficient method to help patients avoid unnecessary biopsy.MethodsA total of 75 patients with breast diseases classified as BI-RADS 4 (45 with malignant lesions and 30 with benign lesions) were prospectively enrolled in this study. T1-weighted imaging (T1WI), T2WI, DWI, and syMRI were performed at 3.0 T. Relaxation time (T1 and T2), apparent diffusion coefficient (ADC), conventional MRI features, and clinical features were assessed. “T” represents the relaxation time value of the region of interest pre-contrast scanning, and “T+” represents the value post-contrast scanning. The rate of change in the T value between pre- and post-contrast scanning was represented by ΔT%.ResultsΔT1%, T2, ADC, age, body mass index (BMI), menopause, irregular margins, and heterogeneous internal enhancement pattern were significantly associated with a breast cancer diagnosis in the multivariable logistic regression analysis. Based on the above parameters, four models were established: model 1 (BI-RADS model, including all conventional MRI features recommended by BI-RADS lexicon), model 2 (relaxation time model, including ΔT1% and T2), model 3 [multi-parameter (mp)MRI model, including ΔT1%, T2, ADC, margin, and internal enhancement pattern], and model 4 (combined image and clinical model, including ΔT1%, T2, ADC, margin, internal enhancement pattern, age, BMI, and menopausal state). Among these, model 4 has the best diagnostic performance, followed by models 3, 2, and 1.ConclusionsThe mpMRI model with DCE-MRI, DWI, and syMRI is a robust tool for evaluating the malignancies in BI-RADS 4 lesions. The clinical features could further improve the diagnostic performance of the model.

PurposeTo compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world.MethodsAccording to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model.ResultsIncluded in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371–0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763–1.172, P, 0.609). For overall survival, there was no significant difference between the two groups.ConclusionThe HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04249440.

Background Accurate predictions of distant metastasis (DM) in locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (nCRT) are helpful in developing appropriate treatment plans. This study aimed to perform DM prediction through deep learning radiomics. Methods We retrospectively sampled 235 patients receiving nCRT with the minimum 36 months’ postoperative follow-up from three hospitals. Through transfer learning, a deep learning radiomic signature (DLRS) based on multiparametric magnetic resonance imaging (MRI) was constructed. A nomogram was established integrating deep MRI information and clinicopathologic factors for better prediction. Harrell's concordance index (C-index) and time-dependent receiver operating characteristic (ROC) were used as performance metrics. Furthermore, the risk of DM in patients with different response to nCRT was evaluated with the nomogram. Findings DLRS performed well in DM prediction, with a C-index of 0·747 and an area under curve (AUC) at three years of 0·894 in the validation cohort. The performance of nomogram was better, with a C-index of 0·775. In addition, the nomogram could stratify patients with different responses to nCRT into high- and low-risk groups of DM (P Interpretation MRI-based deep learning radiomics had potential in predicting the DM of LARC patients receiving nCRT and could help evaluate the risk of DM in patients who have different responses to nCRT. Funding The funding bodies that contributed to this study are listed in the Acknowledgements section.

Summary Background Pulmonary hypertension incidence based on echocardiographic estimates of pulmonary artery systolic pressure in people living with HIV remains unstudied. We aimed to determine whether people living with HIV have higher incidence and risk of pulmonary hypertension than uninfected individuals. Methods In this retrospective cohort study, we evaluated data from participants in the Veterans Aging Cohort Study (VACS) referred for echocardiography with baseline pulmonary artery systolic pressure measures of 35 mm Hg or less. Incident pulmonary hypertension was defined as pulmonary artery systolic pressure higher than 35 mm Hg on subsequent echocardiogram. We used Poisson regression to estimate incidence rates (IRs) of pulmonary hypertension by HIV status. We then estimated hazard ratios (HRs) by HIV status using Cox proportional hazards regression. We further categorised veterans with HIV by CD4 count or HIV viral load to assess the association between pulmonary hypertension risk and HIV severity. Models included age, sex, race or ethnicity, prevalent heart failure, chronic obstructive pulmonary disease, hypertension, smoking status, diabetes, body-mass index, estimated glomerular filtration rate, hepatitis C virus infection, liver cirrhosis, and drug use as covariates. Findings Of 21 314 VACS participants with at least one measured PASP on or after April 1, 2003, 13 028 VACS participants were included in the analytic sample (4174 [32%] with HIV and 8854 [68%] without HIV). Median age was 58 years and 12 657 (97%) were male. Median follow-up time was 3·1 years (IQR 0·9–6·8) spanning from April 1, 2003, to Sept 30, 2017. Unadjusted IRs per 1000 person-years were higher in veterans with HIV (IR 28·6 [95% CI 26·1–31·3]) than in veterans without HIV (IR 23·4 [21·9–24·9]; p=0·0004). The risk of incident pulmonary hypertension was higher among veterans with HIV than among veterans without HIV (unadjusted HR 1·25 [95% CI 1·12–1·40], p

Purpose: We evaluated the performance of the newly proposed radiomics of multiparametric MRI (RMM), developed and validated based on a multicenter dataset adopting a radiomic strategy, for pretreatment prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer. Experimental Design: A total of 586 potentially eligible patients were retrospectively enrolled from four hospitals (primary cohort and external validation cohort 1–3). Quantitative imaging features were extracted from T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging before NAC for each patient. With features selected using a coarse to fine feature selection strategy, four radiomic signatures were constructed based on each of the three MRI sequences and their combination. RMM was developed based on the best radiomic signature incorporating with independent clinicopathologic risk factors. The performance of RMM was assessed with respect to its discrimination and clinical usefulness, and compared with that of clinical information–based prediction model. Results: Radiomic signature combining multiparametric MRI achieved an AUC of 0.79 (the highest among the four radiomic signatures). The signature further achieved good performances in hormone receptor–positive and HER2-negative group and triple-negative group. RMM yielded an AUC of 0.86, which was significantly higher than that of clinical model in two of the three external validation cohorts. Conclusions: The study suggested a possibility that RMM provided a potential tool to develop a model for predicting pCR to NAC in breast cancer.

HIV-infected (HIV+) women may be more vulnerable to neurocognitive impairment (NCI) due to psychological and physiological factors but previous studies show mixed findings. We investigated the neurocognitive performances in HIV+ versus HIV- women and men. This cross-sectional analysis included 669 HIV+ patients (223 women) and 1338 HIV-uninfected (HIV-) controls (446 women) which were frequency matched on sex, education, and 5-year age categories. NCI was screened using the Mini-mental State Examination. Psychomotor speed was assessed using timed alternating hand sequence test. Prevalence of NCI was higher among women versus men in the HIV+ group (16.1% vs 10.5%) but not the HIV- group (4.3% vs 3.5%). HIV+ women performed worse compared to men on psychomotor speed, orientation, attention, and calculation, whereas HIV- women performed worse compared to men on attention and calculation. Adjusted interaction effects of HIV status × sex (women vs men) were significant on orientation, attention, and calculation, and marginally significant on psychomotor speed (p = 0.053). In multivariable models, among both HIV+ women and men, less years of education and depressive symptoms were associated with NCI. Waist-to-hip ratio above the cut-off was strongly associated with NCI among HIV+ women. HIV+ women perform worse on cognitive measures compared to HIV+ men. The association of central obesity with NCI in HIV+ women should be noted.

Gram-negative bacteria, containing toxic proinflammatory and pyrogenic substances [endotoxin or lipopolysaccharide (LPS)], can lead to infection and associated serious diseases, such as sepsis and septic shock. Development of antimicrobial materials with intrinsically endotoxin adsorption activity can prevent the release of bacterial toxic components while killing bacteria. Herein, a series of imidazolium-type polyurethane (PU) foams with antimicrobial properties were synthesized. The content effects of cationic moieties on the antimicrobial activities against Gram-negative Escherichia coli and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus as well as the endotoxin adsorption property were investigated. The obtained PU foams show slightly higher efficiency against two Gram-negative strains than for Gram-positive one and high absorbability of LPS. A wound healing test using P. aeruginosa and its isolated LPS-treated mice as the models further demonstrated that imidazolium-type PU foams combine both antibacterial and endotoxin adsorption properties and may have a potential application as an antimicrobial wound dressing in a clinical setting.

Background: Predicting the neoadjuvant chemoradiotherapy (nCRT) response for patient with locally advanced rectal cancer (LARC) would facilitate therapeutic decisions. Yet, the approach to predict the treatment response before nCRT remains challenging. Here, we develop a multicenter deep learning model based on the pretreatment whole slide image (WSI) of hematoxylin and eosin (H&E) stained biopsy to distinguish the pathological complete response (pCR) from the LARC patients. Methods: Consecutive patients with WSI of endoscopic biopsy H&E-stained slides were included from two hospitals as a training cohort (n = 303) and a validation cohort (n = 154), respectively. Tissue regions of each WSI of H&E-stained biopsy slides were automatically segmented and subjected to extract deep features to construct a deep signature by a VGG-16 convolutional neural network model. A prediction model combining the deep signature with clinicopathologic predictors was developed and validated to identify the pCR group. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) was used to calculate the predictive performance. Findings: The combined model showed good discrimination of the pCR group in two cohorts [the average area under ROC (95% confidence interval): 0.87 (0.83-0.91) in the training cohort, and 0.79 (0.71-0.86) in the independent validation cohort]. Besides, DCA proved that the combined model was clinically valuable. Interpretation: The deep learning model based on biopsy WSI indicates that it might offer a simple preoperative tool to predicts nCRT treatment response for LARC patients. Funding Information: This study was funded by research grants from the National Natural Science Foundation of China [82001986], National Science Fund for Distinguished Young Scholars [81925023], National Key Research and Development Program of China [2017YFC1309102], the Applied Basic Research Projects of Yunnan Province, China [2019FE001-083 and 2018FE001-065], Yunnan digitalization, development and application of biotic resource [202002AA100007]. Declaration of Interests: The authors declare that there are no conflicts of interest. Ethics Approval Statement: The ethics committees of the Sixth Affiliated Hospital of Sun Yat-sen University (SYSU6) and Yunnan Cancer Hospital (YNCH) both approved the multicenter retrospective study. The board waived the requirement for informed consent because of the study’s retrospective nature. All data in the study were de-identified and anonymized.

Background: Prolonged QT interval on electrocardiogram reflects abnormalities in ventricular repolarization may contribute to the greater risk for sudden cardiac death among people living with HIV (PLWH). We investigated whether HIV infection is associated with corrected QT intervals. Methods: Data was derived from baseline assessment of Comparative HIV and Aging Research in Taizhou (CHART), China, 1452 PLWH and 3524 HIV-negative individuals were included. QT correction was performed with Bazett, Fridericia, Framingham and Hodges formulas. QT prolongation was defined as corrected QT interval ≥460 ms in females and ≥450 ms in males. Results: In multivariable models adjusting for traditional risk factors, there was a significantly 3.3 ms (95% confidence interval [CI] 1.7‒10.4) longer mean QTcBazett, 3.0 ms (1.5‒4.4) QTcFramingham, 3.7 ms (2.2‒5.2) QTcHodges and 3.4 ms (1.8‒4.9) QTcFridericia in PLWH vs HIV-negative individuals. Bazett detected the highest prevalence of QTc prolongation in PLWH especially those with resting heart rate (RHR) >100 bpm and significant difference between two groups. Regardless of formula used, older age, female sex, lower LDL, hypertension, lower eGFR, ECG-left ventricular hypertrophy, longer duration since HIV diagnosis and higher HIV RNA were associated with longer QTc intervals among PLWH. Conclusions: HIV infection is independently associated with longer QTc intevals, such risk increases with the infection prolonged and at high HIV RNA. Bazett formula is not recommended for PLWH as they tend to have faster RHR. Additional longitudinal investigations into the prognostic values of QTc intervals in combination with other ECG parameters for incident CVD events are warranted among PLWH.

Background: To develop and validate a radiomic signature for the prediction of lymph node metastasis (LNM) in T1 colorectal cancer (CRC) patients by utilizing common, non-invasive, clinical imaging data. With this signature, patients with T1 CRC at a lower-risk of LNM may avoid extensive radical surgical treatments required in high-risk cases. Methods: This retrospective analysis included 559 T1 CRC patients enrolled at three hospitals. Key radiomic features were extracted from CT images and T2w-MR images using a coarse-to-fine feature selection strategy. These features were used to generate three radiomic signatures based on CT, MR and combined (CT&MR) imaging data. The performance of these radiomic signatures were compared within the primary and external validation cohorts. Furthermore, their prediction performance and clinical usefulness were measured and compared with those of a clinical information-based model. Findings: The radiomic signature combining CT and MR images achieved AUCs of 0.872 (95% CI, 0.770-0.974) in the primary cohort and 0.812 (95% CI, 0.709-0.915) in validation cohort 1, which were significantly better than those of other prediction models. More importantly, the signature achieved high negative predictive values (95.5% in the primary cohort and 97.9% in the validation cohort 1). The decision curve analysis demonstrated the clinical usefulness of this signature. Interpretation: The study suggests that the radiomic signature can accurately predict LNM in cases of T1 CRC. Furthermore, combining CT and MR images can achieve better performance. Specifically, the radiomic signature can potentially reduce overtreatment in patients who were misdiagnosed as LNM+. Funding: This work was supported by grants from the National Natural Science Foundation of China (Nos. 81922040, 81920108026, 81871964, 81930053, 81227901, and 81527805), the National Ten Thousand Plan Young Top Talents (for Dr. Yanlei Ma), the Shanghai Young Top Talents (for Dr. Yanlei Ma. No. QNBJ1701), the Shanghai Science and Technology Development Fund (No.19410713300), CSCO-Roche Tumor Research Fund (No. Y-2019Roche-079), the Fudan Outstanding Young Talent Training Plan (No.YJYQ201601), and the Shanghai Pujiang Program (No.17PJD007), the Beijing Natural Science Foundation under Grant No. 7182109, the National Key Research and Development Plan of China under Grant Nos. 2017YFA0205200, the Youth Innovation Promotion Association CAS (grant number 2019136). Declaration of Interest: The authors indicated no potential conflicts of interest. Ethical Approval: The study protocol complied with the Declaration of Helsinki and was approved by the ethics committee of each participating hospital.

ObjectivesThe HIV epidemic is around 7%–20% among men who have sex with men (MSM) in Southwest China. The low HIV-testing rate highlights the need for tools to identify high-risk MSM in resource-limited regions. Our aim was, therefore, to evaluate the HIV RISK Assessment Tool for HIV prediction and to characterise the primary infection among MSM in Southwest China.DesignA cross-sectional survey was conducted in Guizhou province between January and December 2018. Participants were recruited from gay communities, among whom the HIV RISK Assessment Tool was evaluated. Logistic regression was used to analyse items associated with HIV and the area under the curve (AUC) of the receiver operating curve was calculated to quantify discrimination performance.Participants1330 MSM participants, of which 83 (6.2%) tested as HIV positive.ResultsA higher composite score of the tool (adjusted OR (aOR) 9.33, 95% CI 4.57 to 19.05) was independently associated with HIV infection. Items positively associated with HIV infection included having 2–5 same sex partners (aOR 2.43, 95% CI 1.28 to 4.64), always (aOR 5.93, 95% CI 1.59 to 22.13) or sometimes (aOR 4.25, 95% CI 2.09 to 8.64) having unprotected anal intercourse, taking both insertive and receptive sex roles (aOR 4.95, 95% CI 2.57 to 9.53) or only the receptive sex role (aOR 2.26, 95% CI 1.21 to 4.24). The tool showed an optimal discrimination ability (AUC=0.827), with a specificity of 0.747 and sensitivity of 0.785. Five MSM were identified with primary infection and had similar sexual risk behaviors as HIV-positive participants.ConclusionsThe HIV RISK Assessment Tool showed an overall good performance in predicting HIV risk among MSM in Guizhou province where the prevalence is still severe. This tool also demonstrated a potential to identify primary infection and is worth being promoted in resource-limited regions.

Key Points Question Can deep learning identify preoperative noninvasive lymph node metastasis diagnosis in cervical cancer? Findings This diagnostic study including a total of 479 patients developed a deep learning model to preoperatively and noninvasively identify lymph node metastasis on magnetic resonance imaging, achieving an area under the receiver operating characteristic curve of 0.933 in the independent validation cohort. The predicted lymph node metastasis probability was significantly associated with prognosis of cervical cancer. Meaning Findings from this study suggest that deep learning can be used as a preoperative noninvasive tool for diagnosing lymph node metastasis in cervical cancer., Importance Accurate identification of lymph node metastasis preoperatively and noninvasively in patients with cervical cancer can avoid unnecessary surgical intervention and benefit treatment planning. Objective To develop a deep learning model using preoperative magnetic resonance imaging for prediction of lymph node metastasis in cervical cancer. Design, Setting, and Participants This diagnostic study developed an end-to-end deep learning model to identify lymph node metastasis in cervical cancer using magnetic resonance imaging (MRI). A total of 894 patients with stage IB to IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were reviewed. All patients underwent radical hysterectomy and pelvic lymphadenectomy, received pelvic MRI within 2 weeks before the operations, had no concurrent cancers, and received no preoperative treatment. To achieve the optimal model, the diagnostic value of 3 MRI sequences was compared, and the outcomes in the intratumoral and peritumoral regions were explored. To mine tumor information from both image and clinicopathologic levels, a hybrid model was built and its prognostic value was assessed by Kaplan-Meier analysis. The deep learning model and hybrid model were developed on a primary cohort consisting of 338 patients (218 patients from Sun Yat-sen University Cancer Center, Guangzhou, China, between January 2011 and December 2017 and 120 patients from Henan Provincial People's Hospital, Zhengzhou, China, between December 2016 and June 2018). The models then were evaluated on an independent validation cohort consisting of 141 patients from Yunnan Cancer Hospital, Kunming, China, between January 2011 and December 2017. Main Outcomes and Measures The primary diagnostic outcome was lymph node metastasis status, with the pathologic characteristics diagnosed by lymphadenectomy. The secondary primary clinical outcome was survival. The primary diagnostic outcome was assessed by receiver operating characteristic (area under the curve [AUC]) analysis; the primary clinical outcome was assessed by Kaplan-Meier survival analysis. Results A total of 479 patients (mean [SD] age, 49.1 [9.7] years) fulfilled the eligibility criteria and were enrolled in the primary (n = 338) and validation (n = 141) cohorts. A total of 71 patients (21.0%) in the primary cohort and 32 patients (22.7%) in the validation cohort had lymph node metastais confirmed by lymphadenectomy. Among the 3 image sequences, the deep learning model that used both intratumoral and peritumoral regions on contrast-enhanced T1-weighted imaging showed the best performance (AUC, 0.844; 95% CI, 0.780-0.907). These results were further improved in a hybrid model that combined tumor image information mined by deep learning model and MRI-reported lymph node status (AUC, 0.933; 95% CI, 0.887-0.979). Moreover, the hybrid model was significantly associated with disease-free survival from cervical cancer (hazard ratio, 4.59; 95% CI, 2.04-10.31; P, This diagnostic study develops a machine learning tool for use in preoperative noninvasive identification of lymph metastasis on magnetic resonance imaging in patients with cervical cancer.

Background: Accurate identification of lymph node metastasis (LNM) preoperatively in patients with cervical cancer (CC) can avoid unnecessary surgical intervention and benefit treatment planning. In this study, we aimed to develop a deep learning (DL) model using magnetic resonance imaging (MRI) for non-invasive and preoperative LNM prediction in CC. Methods: This research retrospectively enrolled 479 patients with CC from three centres, and divided patients into a primary cohort (n = 338 from two centres) and an independent validation cohort (n = 141 from another centre). We proposed an end-to-end DL model to identify LNM in CC using MRI, compared the performance among three MRI sequences, and explored the effect of intratumoural and peritumoural regions. Moreover, we built a hybrid model to combine the DL model and clinical information, and assessed its prognostic value in predicting disease-free survival (DFS) of CC by Kaplan-Meier analysis. Findings: Among the three sequences, the DL model which used contrast-enhanced T1-weighted imaging and combined both intratumoural and peritumoural regions (defined as CET1WItumour+peri) showed the best performance (AUC = 0.844 in the validation cohort, P < 0.0001 between the positive and negative LNM patients). These results were further improved in the hybrid model that combined CET1WItumour+peri; and clinical lymph node status (AUC = 0.933 in the validation cohort). Moreover, the H-score from the hybrid model was significantly associated with DFS of CC. Interpretation: DL improves the diagnostic performance of LNM in patients with CC. The hybrid model can be served as an easy-to-use tool to diagnose LNM preoperatively and non-invasively. Funding Statement: This paper is supported by the National Natural Science Foundation of China [Grant No. 81922040, 81930053, 81227901, 61702087]; the Beijing Natural Science Foundation [Grant No. 7182109]; the National Key RD the Strategic Priority Research Program of Chinese Academy of Sciences [Grant No. XDB32030200, XDB01030200]; the Youth Innovation Promotion Association CAS [Grant No. 2019136]. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval was obtained for this retrospective study at every participating centre, and the informed consent from patients was waived.

Purpose: To prospectively investigate changes in quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in patients with cervical cancer before and after neoadjuvant chemotherapy (NACT). Methods: Thirty-eight patients with cervical cancer underwent DCE-MRI and DWI 1 week before and 4 weeks after NACT. The patients were classified into 2 groups: significant reaction (sCR) group and the non-sCR group. DCE-MRI parameters and ADC values were measured and compared between the 2 groups. Results: Before NACT, the mean Ktrans value was higher, but the mean Ve was lower, in the sCR group compared with the non-sCR group; these differences were statistically significant ( ptrans value and the delta (i.e., changed) value of Ktrans were significantly lower in the sCR group compared with the non-sCR group ( ptrans, DKtrans, and pre-mean Ktrans combined with post-mean ADC values were 0.801, 0.955, and 0.878, respectively ( ptrans (0.7020 min−1) and DKtrans (0.0437 min−1). Conclusions: Quantitative parameters (pre-mean Ktrans, DKtrans, and pre-mean Ktrans) combined with post-mean ADC could predict treatment efficacy more precisely. However, quantitative DCE-MRI combined with DWI could not significantly improve prognostic efficacy.

// Jun Yang 1 , Chengde Liao 1 , Yifan Liu 1 , Guangjun Yang 1 , Tengfei Ke 1 , Yingying Ding 1 and Qinqing Li 1 1 Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming 650118, Yunnan, P.R. China Correspondence to: Qinqing Li, email: qinqing_81@163.com Keywords: anti-angiogenic therapy; vascular normalization window; glioma; DCE-MRI; IVIM-MRI Received: August 18, 2017 Accepted: October 28, 2017 Published: November 21, 2017 ABSTRACT The beginning and the end of the vascular normalization window are not clear in response to anti-angiogenic therapies. We used dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion MRI (IVIM-MRI) to noninvasively evaluate the vascular normalization window. MRI was performed five times: before treatment and on the second, fourth, sixth and eighth days of treatment. Quantitative perfusion parameters were calculated at each time point, including the volume transfer coefficient (Ktrans), reverse transfer constant (Kep), pseudodiffusion coefficient (D * ) and perfusion fraction (f). Tumors were evaluated for changes by immunohistochemistry. An increase in Ktrans and Kep was observed after bevacizumab treatment on days 2 and 4. Similar trends were observed for D * and f on days 2 and 4. However, the parameters of Ktrans, Kep, D * and f were decreased on days 6 and 8. A significant increase of the vessel maturity index between the treatment and control groups was measured on days 2 and 4, but this increase abated by days 6 and 8. IVIM and DCE-MRI are helpful when quantifying the tumor perfusion and evaluating the vascular normalization window after anti-vessel therapy. IVIM and DCE-MRI can outline the important period after anti-vessel treatment.

SUMMARYThis cross-sectional study aimed to examine and compare prevalence and correlates of whole blood Epstein–Barr virus (EBV) DNA between HIV-positive and HIV-negative men who have sex with men (MSM). Five hundred and four HIV-positive MSM and 504 age-matched HIV-negative MSM were recruited from an HIV counseling and testing clinic in Shanghai, China from November 2014 to November 2015 and were administered with a face-to-face questionnaire interview. Whole blood EBV DNA was tested by nested polymerase chain reaction assays on EBNA-1, EBNA-2, and LMP-1 genes. The prevalence of whole blood EBV DNA was 56·0% (95% CI 51·7–60·3%) among HIV-positive MSM and 26·0% (95% CI 22·4–30·0%) among HIV-negative MSM. Whole blood EBV DNA positivity was significantly associated with HIV infection (adjusted odds ratio (aOR) 3·43, 95% CI 2·58–4·57) and frequent intake of pickled, smoked, or salty food (aOR 1·71, 95% CI 1·02–2·86) in the whole sample, and with

HIV infection and aging are each associated with neurocognitive impairment (NCI). This study examined the combined effects of HIV infection and aging on NCI. We performed a cross-sectional survey among 345 HIV-infected and 345 HIV-uninfected participants aged at least 40 years. The International HIV Dementia Scale (IHDS) and Chinese version of Mini-mental State Examination (MMSE) were administered to screen for NCI. HIV-infected individuals had higher prevalence of NCI than uninfected individuals (46.7% vs 15.1% for IHDS using cut-off of ≤ 10; 17.1% vs 2.6% for MMSE). Significant main effects of HIV and age were observed on IHDS and MMSE composite scores and all domains except for HIV on attention and calculation. Significant interaction effects between HIV and age were observed on motor speed, orientation, registration and recall, and mainly attributed to the inferior performance of HIV-infected patients aged over 60 years. Among HIV-infected individuals, in multivariable logistic models, older age, depressive symptoms and history of nevirapine treatment were associated with NCI using both IHDS and MMSE, whereas lower education current smoker and current CD4 ≥ 800 cells/μL were associated only with NCI using IHDS, and hypertension was associated only with NCI using MMSE. Findings suggest that HIV and older age may confer interactive effects on cognitive function in several domains with older HIV-infected adults experiencing greater NCI, which requires further longitudinal investigation. Furthermore, HIV early diagnosis and treatment may prevent or reverse NCI, but extra attention should be given to adverse effects including metabolic changes associated with long-term treatment.

We examined the effect of combination antiretroviral therapy (cART) on liver fibrosis among HIV-infected patients with or without hepatitis B (HBV) or C virus (HCV) co-infection. This was a retrospective cohort study of HIV-infected patients receiving cART during 2004-2016. Liver fibrosis was assessed using Fibrosis-4 (FIB-4) score with three classifications: Class 1,1.45; Class 2, 1.45-3.25; Class 3,3.25. Of 3900 participants, 68.6% were HIV mono-infected, 5.3% were HIV/HBV co-infected, 23.8% were HIV/HCV co-infected and 2.3% were HIV/HBV/HCV co-infected. Participants received follow-up treatment (median was 3.3 years). Improvement to a lower class was observed in Class 2 (52.6%) and Class 3 (74.2%), respectively. Progression to a higher class was observed in 12.8% and 5.0% in Class 1 and Class 2, respectively, and with a median time of 5.7 months. For improvement to lower classes, older age, male, Dai ethnicity, injection drug use, HCV co-infection and tenofovir for treatment were negative predictors, but in Class 3 of FIB-4 and time-updated increases in CD4 count from baseline were positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity and HCV co-infection were positive predictors, while baseline CD4 count and in Class 2 of FIB-4 were negative predictors. Improvement to lower class linked with decreased mortality risk among patients in Class 3. Early cART initiation for HIV-infected patients with and without hepatitis co-infections may mitigate or slow down some of liver fibrosis, but special attention should be given to those who are older, male, co-infected with HCV.

We assessed the factors that influenced improvement or progression in human immunodeficiency virus (HIV)-infected patients who were receiving combination antiretroviral therapy (cART). This was a retrospective cohort study of HIV-infected patients receiving cART in Taizhou, Zhejiang, China, 2009-2015. Liver fibrosis was assessed by Fibrosis-4 (FIB-4) score. Improvement of liver fibrosis was defined as having > 30% decrease in FIB-4 from baseline, whereas progression of liver fibrosis was defined as having > 30% increase in FIB-4 score from baseline. A total of 955 HIV-infected patients were included. Of these, 808 (84.6%) were HIV-monoinfection, 125 (13.1%) were HIV/hepatitis B virus (HBV) coinfection and 29 (3.0%) were HIV/hepatitis C virus (HCV) coinfection. The median duration of treatment was 15 months. After treatment, 37.1% participants had > 30% decreases in FIB-4 index, 14.8% had > 30% increases in FIB-4 index, while the remaining 48.2% had stabilized FIB-4 index. In multivariate analysis, improvement of liver fibrosis was negatively associated with an older age, but was positively associated with baseline FIB-4 index and > 30% increases in CD4 cell count after ART. Progression of liver fibrosis was positively associated with an older age, but was negatively associated with gender and HIV transmission mode (male homosexual vs. male heterosexual, female heterosexual vs. male heterosexual), and baseline FIB-4 index. Our findings indicate that improvement of liver fibrosis could be achieved by early initiation of ART through better CD4 cell recovery. Liver fibrosis and hepatotoxicity associated with ART should be monitored as early as possible and throughout till the end of treatment, with special attention to the elderly and heterosexual men.

Preoperative 5-fluorouracil (5-FU) based chemoradiation is regarded as the standard treatment for locally advanced colorectal cancer (CRC). However, advances in using 5-FU in chemoradiotherapy treatment of CRC are limited by the resistant to the chemoradiotherapy. It has been demonstrated that aberrant methylation contributes to radioresistance in a human colorectal tumor cell line. So we analyzed the differential DNA methylation patterns by methylationspecific microarray in a 5-FU-based concurrent chemoradiotherapy resistance cell model which was established by using human CRC cell line HCT116. As a result, we detected a total of 3719 hypomethylated sites and 27940 hypermethylated sites in CRR cells compared to the control. Furthermore, we analyzed top 10 GO terms involved in significantly differential DNA methylation patterns resulted from the 5-FU-based CRR through GO analyses. To further explore the molecular basis of 5-FU-based CRR in CRC cells, CYP1B1 and CYP2C9 genes expression level were shown down regulated by qRT-PCR. These findings might provide a novel insight for chemoradiation resistance in CRC and provide a potential therapy method in CRC patients.

Objective Advanced parental age has raised additional concern as a risk factor of autism. We conducted a meta-analysis of observational studies investigating the association between advanced parental age and risk of autism. Method PubMed, EMBASE, and Web of Science were searched for reports published up to November 11, 2015. Risk estimates from individual studies were pooled using random-effects models. Results Twenty-seven studies were included in the meta-analysis. Compared with the reference points, the lowest parental age category was associated with a reduced risk of autism in the offspring, with adjusted odds ratios (ORs) 0.89 (95% confidence intervals [CIs] 0.75–1.06) and 0.81 (95% CI 0.73–0.89) for mother and father, respectively, and the highest parental age category was associated with an increased risk of autism in the offspring, with adjusted ORs 1.41 (95% CI 1.29–1.55) and 1.55 (95% CI 1.39–1.73) for mother and father respectively. Dose–response meta-analysis indicated that an increase of 10 years in maternal and paternal age was associated with an 18% and 21% higher risk of autism. Conclusion Advanced parental age was associated with an increased risk of autism in the offspring. More mechanistic studies are needed to further explain this positive association.

Pre-treatment survival prediction plays a key role in many diseases. We aimed to determine the prognostic value of pre-treatment Magnetic Resonance Imaging (MRI) based radiomic score for disease-free survival (DFS) in patients with early-stage (IB-IIA) cervical cancer. Methods: A total of 248 patients with early-stage cervical cancer underwent radical hysterectomy were included from two institutions between January 1, 2011 and December 31, 2017, whose MR imaging data, clinicopathological data and DFS data were collected. Patients data were randomly divided into the training cohort (n = 166) and the validation cohort (n=82). Radiomic features were extracted from the pre-treatment T2-weighted (T2w) and contrast-enhanced T1-weighted (CET1w) MR imagings for each patient. Least absolute shrinkage and selection operator (LASSO) regression and Cox proportional hazard model were applied to construct radiomic score (Rad-score). According to the cutoff of Rad-score, patients were divided into low- and high- risk groups. Pearson's correlation and Kaplan-Meier analysis were used to evaluate the association of Rad-score with DFS. A combined model incorporating Rad-score, lymph node metastasis (LNM) and lymphovascular space invasion (LVI) by multivariate Cox proportional hazard model was constructed to estimate DFS individually. Results: Higher Rad-scores were significantly associated with worse DFS in the training and validation cohorts (P

OBJECTIVES The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the interaction of the effects of aging, baseline renal impairment, and stages of HIV infection on post-treatment changes in renal function. METHODS This analysis included 5533 HIV-infected patients on cART in 2004-2016. Progression to chronic kidney disease (CKD) was defined as either two consecutive estimated glomerular filtration rate (eGFR) measurements

Increasing evidence shows that mitochondrial DNA (mtDNA) variations have an important effect on metabolic disorders, but such studies have not been conducted in HIV-infected patients in Asia. We investigated the distribution of mtDNA haplogroups and their correlation with metabolic disorders in HIV-infected patients. A cross-sectional survey was performed among 296 HIV patients older than the age of 40 years in a rural prefecture, Eastern China. The entire mtDNA sequence was amplified by polymerase chain reaction using four overlapping pairs of primers that have been standardly used. In this sample, mtDNA haplogroups B, D, M7, and F were the most dominant haplogroups. The overall prevalence of metabolic syndrome (MetS) was 36.1%, and was highest (77.8%) among those with haplogroup G and lowest (21.4%) among those with haplogroup M8. In multivariable analysis, haplogroups G and N9 were significantly associated with the presence of MetS [adjusted odds ratio (aOR) = 13.5, 95% confidence interval (CI): 1.9-94.7; aOR = 8.1, 95% CI: 1.8-36.1; respectively]. Moreover, patients with haplogroup G had increased odds of elevated glycated hemoglobin (HbA1c) (aOR = 10.1, 95% CI: 1.4-71.1), patients with haplogroup N9 had increased odds of elevated triglycerides (aOR = 13.5, 95% CI: 2.4-76.8). No significant association between mtDNA haplogroups and other MetS components was observed. Our data demonstrate the association between mtDNA haplogroups and MetS in HIV-infected patients. The Asian-specific mtDNA haplogroups G and N9 may confer higher risk for the development of MetS in HIV-infected patients, which requires further longitudinal investigation.

Inconclusive results have been reported in studies evaluating the association between HIV infection and subclinical atherosclerosis. Unsolved issues include whether the increased atherosclerosis burden observed in some studies is attributed to greater prevalence of traditional risk factors or HIV infection. Therefore, we evaluated the association of HIV infection with subclinical atherosclerosis as assessed by carotid artery intima-media thickness, while controlling for the effects of traditional risk factors as operationalised by the Framingham risk score (FRS).We did a cross-sectional evaluation of data derived from the baseline assessment of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, an ongoing longitudinal study being done in Zhejiang province, China. HIV-positive and HIV-negative individuals aged 18 years and older were recruited between Feb 1, and Dec 10, 2017, and were frequency-matched for age and sex in a 1:2 ratio. Subclinical atherosclerosis was defined as carotid artery intima-media thickness of 780 μm or higher. Logistic regression was used to assess the associations of HIV-positive serostatus and FRS with subclinical atherosclerosis.480 of 1425 (36·1%, 95% CI 33·6-38·6) HIV-positive and 784 of 2850 (27·5%, 95% CI 25·9-29·2) HIV-negative individuals had subclinical atherosclerosis (p0·0001), and these patterns remained significant (adjusted odds ratio [adjOR] 1·72, 95% CI 1·47-2·01) in the adjusted model. After stratifying by age, higher prevalence of subclinical atherosclerosis was observed in HIV-positive than in HIV-negative individuals across the age groups 18-29 years (41 [16·0%] of 256 vs 13 [2·5%] of 512, p0·0001), 30-44 years (128 [24·0%] of 533 vs 153 [14·4%] of 1066, p0·0001), and 45-59 years (182 [46·6%] of 391 vs 294 [37·6%] of 782, p=0·0032), but not 60-75 years (163 [66·5%] of 245 vs 324 [66·1%] of 490, p=0·912). Significant negative interaction between HIV-positive serostatus and age on subclinical atherosclerosis was observed (p0·0001). ORs adjusted for age, sex, and FRS were 8·84 (95% CI 4·50-17·34) for the age group 18-29 years, 2·09 (1·59-2·74) for 30-44 years, 1·54 (1·19-1·98) for 45-59 years, and 1·04 (0·75-1·44) for 60-75 years. Among HIV-positive individuals, none of the HIV-specific variables were significantly associated with carotid artery intima-media thickness estimates except for being antiretroviral therapy naive.HIV infection is associated with subclinical atherosclerosis, independent of classic risk factors. The association is stronger at younger ages, suggesting early onset of subclinical atherosclerosis among young adults. These findings highlight the need to modify HIV/AIDS treatment guidelines to incorporate cardiovascular evaluation in China.China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, and Shanghai Municipal Health and Family Planning Commission.

End-stage liver disease (ESLD) is among leading causes of death for people living with HIV and HCV. Little is known how liver fibrosis score predicts mortality in HIV/HCV co-infected population under combination antiretroviral therapy (cART). A retrospective cohort study of 691 HIV/HCV co-infected patients receiving cART in Yunnan, China from 2005 to 2016 was carried out to explore the association between Fibrosis-4 index (FIB-4) and all-cause mortality. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for FIB-4 and covariates. After a median follow-up of 4.8 years with a total follow-up time of 3,696 person-years (PY), 131 deaths occurred and the all-cause mortality was 3.5 per 100 PY. The mortality was 2.9 (95% CI: 2.3-3.5)/100 PY for the FIB-4 ≤ 3.25 group and 5.8 (4.2-7.4)/100 PY for the FIB-4 > 3.25 group at baseline. People with FIB-4 changed from mild to advanced group showed HR of 1.81 (95% CI: 1.01-3.25) for death, and with FIB-4 sustaining advanced showed HR of 3.11 (1.75-5.54), both compared to those with FIB-4 remained mild, while lower risk of death was observed among married people (HR = 0.63, 95% CI: 0.41-0.99) compared to unmarried, among those with most recent CD4+ T cell counts between 200 and 350 cells/μL (0.50, 0.30-0.86) and > 350 cells/μL (0.25, 0.15-0.41) compared to CD4 under 200 cells/μL. Advanced and progressive liver fibrosis is a strong predictor of all-cause mortality in HIV/HCV co-infected patients under cART in China.

This study aims to investigate the prevalence and genotype distribution of anal human papillomavirus (HPV) infection among men with different sexual orientations with or without human immunodeficiency virus (HIV) in China. A cross-sectional study was conducted during 2016–2017 in Taizhou City, Zhejiang Province. Convenient sampling was used to recruit male participants from HIV voluntary counselling and testing clinics and Center for Disease Control and Prevention. A face-to-face questionnaire interview was administered and an anal-canal swab was collected for HPV genotyping. A total of 160 HIV-positive and 113 HIV-negative men participated in the study. The prevalence of any type HPV was 30.6% for heterosexual men, 74.1% for homosexual and 63.6% for bisexual men among HIV-positive participants, while the prevalence was 8.3%, 29.2% and 23.8% respectively among HIV-negatives. The most prevalent genotypes were HPV-58 (16.9%), HPV-6 (15.6%) and HPV-11 (15.0%) among HIV-positive men, and were HPV-16 (4.4%), HPV-52 (4.4%) and HPV-6 (3.5%) among HIV-negative men. Having ever had haemorrhoids and having ever seen blood on tissue after defaecation was associated with HPV infection. One-fourth of the HPV infections in this study population can be covered by the quadrivalent vaccine in market. The highly prevalent anal HPV infection among men especially HIV-infected men calls for close observation and further investigation for anal cancer prevention.

Background: Association of postoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer(CRC) remains to be explored. Therefore, we aimed to investigate the association between the postoperative peripheral CD4+ T cells percentage and recurrence in CRC patients. Patients and Methods: Consecutive stage I-III CRC patients without neoadjuvant treatment undergoing curative resection from January 2010 to July 2016 were identified in two Chinese centers. The association between the postoperative CD4+ T cells percentage, measured within 12 weeks after surgery, and recurrence-free survival (RFS) was analyzed. Results: A total of 1028 patients were identified (training set: 913 patients, validation set: 115 patients). In the training set, the 5-year RFS rate of the 441 patients with abnormal postoperative CD4+ T cells percentage was significantly lower than that of those with normal percentage (70.3%[95 %CI 65.7%–75.2%] vs. 77.6%[95%CI 73.7%–81.7%]; unadjusted hazard ratio[HR] 1.36[95%CI 1.04–1.78], P=0.02). The result was confirmed in the validation set. Multivariable Cox regression analysis demonstrated that the association of postoperative CD4+ T cells percentage with 5-year RFS was independent both in the training and validation sets. In propensity score matching analysis, patients with normal postoperative CD4+ T cells percentage were found to have a favourable response to adjuvant chemotherapy (HR 0.29 [95% CI 0.12–0.72], P=0.008). Conclusion: Postoperative peripheral CD4+ T cells percentage is a predictive biomarker for RFS in patients with CRC, which can identify those who will benefit from adjuvant chemotherapy. Funding Statement: This work was supported by grants from the National Key Research and Development Program of China [2017YFC1309100], the National Natural Scientific Foundation of China [81771912], and the Applied Basic Research Projects of Yunnan Province, China [2018FE001- 065 and 2018FE001-251]. Declaration of Interests: The authors declare that they have no potential conflicts of interest. Ethics Approval Statement: This retrospective study was approved by the institutional review board of each participating hospital. The requirement for informed consent was waived by the board, owing to the study's retrospective nature. All the patient data in the survey were anonymized.

Background: Association of preoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer(CRC) remains to be explored. Therefore, we aimed to investigate the association between the preoperative peripheral CD4+ T cells percentage and recurrence in CRC patients. Patients and Methods: Consecutive stage I-III CRC patients undergoing curative resection from January 2010 to July 2016 were identified. Preoperative peripheral CD4+ T cells percentage was measured within one week before surgery. The association between the preoperative CD4+ T cells percentage and recurrence-free survival(RFS) was analyzed. Results: A total of 1248 patients were identified. Normal preoperative CD4+ T cells percentage was present in 47.8% of patients and was associated with a better survival (median RFS: 49 months vs. 43 months in patients with elevated percentage, P=0.33; vs. 46 months in those with reduced percentage, P=0.008). Patients with normal percentage had a 5- year RFS of 80.7% versus 75.4% in those with elevated percentage (hazard ratio[HR]:1.19, 95%CI:0.86-1.66; P=0.31) and 72.1% in those with reduced percentage (HR:1.47, 95%CI:1.12-1.92; P=0.005). In terms of the >2-5 years RFS, it was 93.3% in patients with normal percentage versus 86.2% in those with elevated percentage (HR:1.96, 95% CI:1.12-3.43; P=0.02) and 86.4% in those with reduced percentage (HR:2.02, 95%CI:1.25-3.28; P=0.004). Elevated and reduced preoperative CD4+ T cells percentage remained significant for >2-5 years RFS on multivariate analysis. Conclusion: Preoperative peripheral CD4+ T cells percentage was associated with the recurrence after 2 years following surgery in CRC. Funding Statement: This work was supported by grants from the National Key Research and Development Program of China [2017YFC1309100], the National Natural Scientific Foundation of China [81771912], and the Applied Basic Research Projects of Yunnan Province, China [2018FE001-065 and 2018FE001-251]. Declaration of Interests: The authors declare that they have no potential conflicts of interest. Ethics Approval Statement: This retrospective study was approved by the institutional review board of the Yunnan Cancer Center. The requirement for informed consent was waived by the board, owing to the study's retrospective nature. All the patient data in the survey were anonymized.

Purpose To observe the longitudinal changes in peripheral nerve repaired with chitosan conduits in a rat model of radiation-induced neuropathy. Materials and methods Four months after 40 Gy radiation to the right lower limbs, forty-two rats were divided randomly into three groups. Chitosan conduits were implanted with (group A, n=12) or without (group B, n=12) mesenchymal stem cells (MSCs), and untreated controls (group C, n=12). Following sciatic nerve MR imaging (including T2WI and Gd-DTPA enhanced T1WI), functional evaluation and electrophysiological exam were performed two-monthly, final histological assessments were done at the end of one year. The differences among the experimental and control groups were statistically analysed with Fisher's PLSD or t-test. Results The compound muscle action potentials (CMAPs) and sciatic function index (SFI) had declined since 4 months after radiation injury. The focal nerve enlargement and hyperintensity, the perineurium and connecting muscle enhancement were demonstrated by MR neurography images. After chitosan tube implantation, the normalized signal intensities (SIs) in group A were declined more rapidly than SIs in other groups. The histological assessments indicated that group A had better remyelination, combined with higher CMAPs amplitude and SFI score than other groups. Conclusion A single fraction dose of 40 Gy can be used to establish a rat model of sciatic nerve injury. Longitudinal electrophysiological examination and MR neurography are useful to evaluate the post-irradiation sciatic neuropathy. The rats with tissue-engineered conduits implantation showed some improvement of lower limb function, accompanied by a normalization of (T1W/T2W) MR signal.

Background In view of the inability of traditional etiological methods to diagnose pulmonary tuberculosis rapidly and effectively, the antibody responses against 38kD and 16kD-antigens of Mycobacterium tuberculosis (M. tuberculosis) were both detected in order to obtain a better serological detection method for M. tuberculosis. Methods M. tuberculosis-secreted protein 38kD and membrane protein 16kD were prokaryotically expressed and purified, and then used as detection antigens. A novel evolved immunoglobulin-binding molecule (NEIBM)-ELISA method was used to detect antibody levels against 38kD and 16kD in active tuberculosis patients (confirmed tuberculosis cases and clinically diagnosed cases), to explore the significance of these two antigens in serological detection of M. tuberculosis, and to study the diagnostic value of the combined detection of the two antigens in active pulmonary tuberculosis. Results The results showed that the positive detection rates of the 16kD antigen and 38kD antigen of M. tuberculosis were higher (about 44%) in the confirmed cases of tuberculosis, and there was no significant difference in the positive detection rates of the two antigens (P=0.786). The combined detection of these two antigens showed that the positive detection rate could be increased to 61.5%, which was significantly better than the detection effect of the two antigens alone. The positive detection rates of 16kD and 38kD antigens were 26-30% in clinically diagnosed tuberculosis cases, which were lower than those in confirmed tuberculosis cases, and there was no significant difference in the positive detection rates of the two antigens (P=0.242). The detection effect of the two combined antigens was better than that of the 16kD and 38kD antigens alone, but the detection rate was still lower than that of the confirmed tuberculosis cases. Conclusions This study found that the detection effect of 16kD and 38kD antigens was similar in confirmed cases and clinically diagnosed cases of pulmonary tuberculosis, and that the detection effect needs to be further improved. The combined detection of the two antigens showed a significantly better detection effect than the two antigens alone, suggesting that the combined detection of multiple antigens can be used for serological diagnosis of M. tuberculosis infection in clinic.

To explore the early predictors of post-operative recurrence and metastasis of rectal cancer, analyse the associated risk, and construct a model. Retrospective collection. Four hundred patients with rectal cancer underwent surgical resection and pathological diagnosis from September 2013 to September 2014. During the post-operative period, the patients were tested by imaging examination, serum tumour markers, and routine blood follow-up for at least 3 years. Preoperative CT examination of tumour size, lymphocyte-to-neutrophil ratio, and CEA were significant biomarkers for predicting recurrence and/or metastasis of post-operative rectal cancer. The stratified threshold of the lesion size cut-off point in CT images of patients with rectal cancer was 18.75 cm3, the cut-off point value of the lymphocyte-to-neutrophil ratio was 0.33, and the CEA cut-off point value was 16.97 ng/ml. We used the cut-off point to perform stratified survival analysis to obtain two K-M curves and conduct a log-rank test. The Cox multivariate risk regression results were as follows: preoperative CT images of lesion size, lymphocyte-to-neutrophil ratio, and CEA. The AUC of the normogram model for the prediction of post-operative recurrence and metastasis of rectal cancer is 0.939. Preoperative CT examination of tumour size can predict post-operative recurrence and metastasis of rectal cancer and can be used to analyse its risk. The lymphocyte-to-neutrophil ratio and CEA can also predict post-operative tumour recurrence and metastasis risk.

Epithelial-mesenchymal transition (EMT) is linked to fibrosis following exposure to silica. The scavenger receptor, macrophage receptor with collagenous structure (MARCO) plays an important role in silica-induced inflammation, however, the effect of MARCO on silica-induced fibrosis has not been identified. We hypothesized that MARCO would regulate EMT and be involved in the development of silicosis. Herein, we found that MARCO was highly expressed in lung tissue after exposure to silica and a MARCO inhibitor PolyG could alleviate pulmonary fibrosis in vivo. Our results confirmed that the expression of epithelial marker such as E-cadherin decreased, while the expression of mesenchymal markers, including vimentin and α-SMA increased after silica treatment. Furthermore, PolyG administration efficiently blocked the mRNA and protein expression of EMT markers and decreased the level of fibrosis-related transcription factors and proteins, such as Col1a1, Col3a1, Collagen I and Collagen III in the lungs of silica-exposed rats. The findings demonstrate that the macrophage membrane receptor MARCO controls the fibrotic response through regulating EMT in experimental silicosis and suggest a novel target for preventive intervention.

Objectives In patients with very severe aplastic anemia (VSAA), neutropenia is prolonged and persistent, resulting in refractory overwhelming infections. Hematopoiesis recovery is urgently needed. Methods Six patients with de novo VSAA lacking HLA-identical sibling donors and those who experienced refractory infections underwent haploidentical related donor (HRD) hematopoietic stem cell transplantation (HSCT) as a first-line therapy. The conditioning regimen consisted of busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Culture-expanded allogeneic bone marrow-derived mesenchymal stromal cells were infused on day 0 and day +14. Results From diagnosis to HSCT, 6 patients experienced a total of 28 episodes of persistent fever, and the median number was 4 (range, 3-7). All cases developed major bacterial infections and invasive pulmonary fungal infection pre-HSCT. The median time from diagnosis to HSCT was 2 months (range, 1-3.5 months). All patients achieved sustained, full donor chimerism, and the median time of myeloid recovery and platelet engraftment was 13 days (range, 9-19 days) and 15.5 days (range, 10-23 days), respectively. One patient died of aGVHD, and 5 patients are alive after a median follow-up of 21 months (range 17-40.5). Conclusions Upfront HRD-HSCT may be a safe and promising choice for patients with VSAA in critical situations without suitably matched donors.

Objectives Identification of risk factors is essential for developing herpes simplex virus type 2 (HSV-2) prevention interventions that could also reduce HIV-1 transmission, particularly among HIV-1-discordant couples. Methods A prospective cohort study was conducted among HIV-1-discordant couples from June 2009 to March 2011 in Yunnan province, China. 413 HIV-1-infected partners and 517 HIV-1-uninfected partners who were HSV-2 seronegative or equivocal at enrolment and who had a study partner completing the baseline survey and HSV-2 testing were included in the analysis. Results HSV-2 incidence was 2.9 per 100 person-years (PY) for HIV-1-infected partners and 4.5 per 100 PY for HIV-1-uninfected partners. At least 36% of incident HSV-2 infections were from outside sexual partner. Among HIV-1-infected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those with baseline equivocal HSV-2 result, having an initially HSV-2 seropositive or equivocal partner, reporting no sex with study partner and initiating antiretroviral therapy (ART) during follow-up. Among HIV-1-uninfected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those having an initially HSV-2 seropositive partner and reporting sex with study partner ≥5 times/month, but was lower among those having a partner with baseline CD4 + count ≥350 cells/μL. Conclusions Our findings underscore the importance of developing prevention and intervention programmes to reduce HSV-2 transmission among this population. The relationship between ART initiation and HSV-2 seroconversion requires further investigation.

Cancer is a leading cause of death among people living with HIV/AIDS (PLWHA). We conducted a systematic review and meta-analysis to evaluate prevalence of cancer risk factors among Chinese PLWHA based on 102 articles. Random effects meta-analysis was used to calculate the summary prevalence estimate (sPrev) and 95% confidence interval (CI) for each cancer risk factor by demographic group. Overall, the sPrev for each risk factor among Chinese PLWHA was: 41.1% (95% CI: 35.3–46.9%) for current smoking; 30.3% (95% CI: 23.3–37.4%) for current alcohol consumption; 24.4% (95% CI: 14.7–30.2%) for overweight and obesity; 12.5% (95% CI: 10.6–14.3%) for hepatitis B virus infection; 29.1% (95% CI: 23.6–34.5%) for hepatitis C virus infection; 33.9% (95% CI: 24.3–43.5%) for high-risk human papillomavirus infection from cervical samples and 78.6% (95% CI: 69.4–87.7%) from anal samples; 2.7% (95% CI: 0.7–4.7%) for Epstein-Barr virus (EBV) immunoglobulin M (IgM) positivity, 94.7% (95% CI: 90.7–98.8%) for EBV IgG positivity and 25.6% (95% CI: 12.4–38.8%) for EBV DNA positivity; 14.9% (95% CI: 12.4–17.4%) for human herpes virus 8 infection. The prevalence of major cancer risk factors was high among PLWHA in China, suggesting an urgent need for interventions to reduce cancer risk in this high-risk group.

Zhen-Hui Li,1,* Ding-Yun You,2,* De-Pei Gao,1 Guang-Jun Yang,1 Xing-Xiang Dong,1 Da-Fu Zhang,1 Ying-Ying Ding1 1Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, 2Department of Science and Technology, Kunming Medical University, Kunming, Yunnan, People’s Republic of China *These authors contributed equally to this work Objectives: Most colorectal cancers are classical adenocarcinomas (AC), and less frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC). The purpose of this study was to evaluate the computed tomography (CT) findings that can help to differentiate MAC and SC from AC.Methods: CT scans of 168 patients with pathologically proven MAC and 67 patients with pathologically proven SC were analyzed, and 220 patients with classical AC were also included as a control group. CT findings of the three groups were compared and contrasted in terms of the bowel involvement patterns, contrast enhancement patterns, and presence or absence of bowel obstruction, intratumoral calcification, pericolic fat infiltration, and local tumor extension to adjacent organs. Statistical analyses were made by using the one-way analysis of variance, least significant difference test, and Pearson’s chi-square test.Results: Compared with classical AC, the MAC showed more severe (6.29±2.69 cm vs 4.57±1.74 cm, P

Objective To estimate the prevalence of ever, current and heavy tobacco and alcohol use and their correlates among patients undergoing methadone maintenance treatment (MMT). Design Cross-sectional study. Setting The study was conducted in all of the 5 MMT clinics in Dehong Prefecture, China. Participants 2121 (81.6%) eligible MMT participants were included in the study population. Analysis Ordinal logistic regression was used to estimate the ORs and their 95% CIs. Results The overall prevalence of ever, current and heavy smoking was 98.6%, 97.8% and 66.3%, respectively; while that of ever, current and hazardous alcohol drinking was 86.6%, 58.6% and 16.6%, respectively. Among HIV-infected participants, the proportions of those experiencing harmful effects of tobacco and alcohol on AIDS were 53.6% and 72.5%, respectively, and 16.9% and 49.3% had ever tried to quit after diagnosis with HIV. After adjusting for potential confounders, heavier smokers and more hazardous drinkers were more likely to be men, older and less educated. Ethnic minorities were less likely to heavily smoke, but more likely to engage in hazardous drinking. In addition, hazardous drinking was negatively associated with longer years of MMT and HIV infection. Moreover, heavier smoking (OR ≥2 =2.08, 95% CI 1.16 to 3.73) and more hazardous drinking (OR ≥2 =2.46, 95% CI 1.53 to 3.97) were positively associated with having multiple sexual partners, and both were positively associated with each other. Conclusions The prevalence of tobacco and alcohol consumption was extraordinarily high among MMT participants in China, suggesting the urgent need of enhancing MMT patients9 awareness of the harmful effects of tobacco and alcohol consumption and implementing comprehensive education and effective intervention programmes.

This study aims to examine adverse childhood experiences (ACEs), its interaction with methamphetamine (METH) use (e.g., frequency, duration, and dependence) and METH-associated risk of psychosis.This was a cross-sectional study conducted among METH users at a drug rehabilitation center in China. Participants were assessed using Mini International Neuropsychiatric Interview for METH-associated psychosis.Of 189 participants, 50.5% reported at least one of eight ACE categories and 35.4% had past history of a psychotic episode. After adjusting for age, sex, education, and marital status, all ACE categories except emotional abuse and parental separation or divorce increased the risk of ever experiencing METH-associated psychosis. When comparing participants who reported no ACEs, those with three or more ACEs had higher risks of lifetime psychosis (OR=4.5, 95% CI: 1.6-12.6). Relationship between number of ACEs and lifetime psychosis was graded (p.01). The interaction between frequency of METH use (≥4 vs.4 times/month) and number of ACEs on the risk of METH-associated psychosis was statistically significant (p=0.02), showing a trend of adjusted OR decreased significantly as the number of ACEs increased.These analyses indicate that childhood adversities increase the individual's vulnerability to METH-associated psychosis. Further larger longitudinal studies are warranted.

Introduction: Although steady improvements to chemotherapeutic treatments have helped cure 80% of childhood B-cell acute lymphoblastic leukemia (B-ALL) cases, chemotherapy has proven to be less effective in treating the majority of adult patients, the equivalent rate for adults remains poor at 30-40%, with relapse representing the leading cause of mortality in both children and adults. Development of chemo-resistance is a crucial factor contributing to relapse, therefore understanding the biological mechanisms underlying this resistance is imperative for discovering innovative treatment strategies. Relapse specific/enriched genetic alterations in the emergence of clones that have gained a selective advantage under the pressure of specific chemotherapeutics. We previously performed longitudinal whole-exome sequencing analysis in diagnosis/relapse pairs from adult patients with B-ALL revealed relapse-specific mutations in NR3C1 gene, encoding the glucocorticoid receptor (GCR), are frequently detected. Furthermore, the mutations of NR3C1 identified in relapsed B-ALL patients all resulted in haploinsufficiency for NR3C1. In this study, we sought to delineate whether reduced expression of NR3C1 could give rise to chemo-resistance in B-ALL and elucidate the mechanism responsible for the resistance. Methods: We performed clinical sample and ex vivo cell studies to elucidate the relationship between endogenous expression of NR3C1 in ALL cells and the sensitivity to dexamethasone. We further induced enforced expression of NR3C1 in dexamethasone-resistant ALL cells by being transfected with the expression vector of NR3C1. Moreover, we used CRISRP/CAS9 system to knock out NR3C1 gene in dexamethasone- susceptible ALL cell lines. Finally, we performed whole-genome transcriptome sequencing (RNA-seq) and Western-blotting analysis to elucidate the molecular mechanisms. Results: (1) We examined the correlation of endogenous expression of NR3C1 with the sensitivity to dexamethasone in five human ALL cell lines, Reh, Jurkat, CCRF-CEM, Nalm6 and 6T-CEM. Our data suggested that the susceptibility of ALL cells to dexamethasone was positively correlated with endogenous NR3C1 mRNA and protein level. (2) Enforced expression of NR3C1 in dexamethasone-resistant ALL cells can reverse the resistance; (3) Knockout of NR3C1 gene in dexamethasone- susceptible ALL cells can confer resistance to glucocorticoid. (4) RNA-seq analysis showed that NR3C1 protein involved in the regulation of cell apoptosis, p53 pathway and cell cycle. NR3C1 protein regulated transcription of PI3K-related genes in ALL cells, which diminished PIK3CD transcription and increased mRNA level of PIK3R6, PIK3R5, PIK3R2, AKT3 and GSK3β. In addition, NR3C1 increased transcription of pro-apoptotic genes, BCL2L11 (encoding Bim protein), BMF and BOK, and diminished transcription of anti-apoptotic genes, BCL2 and BAG2. Further Western-blotting confirmed that overexpression of NR3C1 increased protein level of p-AKT (Ser 473), p-GSK3β (Ser 9), Bim and Bad, and diminished protein level of of Bcl-2 and Bcl-xl. Conclusions: Our results provide, for the first time, evidence that haploinsufficiency for NR3C1 in ALL cells causes resistance specifically to glucocorticoid, which are the backbone of induction therapy, by disrupting the activation of PI3K/AKT/GSK3 signaling pathway and the balance between pre-apoptotic proteins and anti-apoptotic proteins. Disclosures No relevant conflicts of interest to declare.

We surveyed 276 club drug users in Shanghai, China. Overall, 43.8 % reported ≥2 sex partners in the past 30 days, and 48.9 % reported having sex with non-regular partners, 67.4 % of whom had unprotected sex. Having ≥2 recent sex partners was associated with being 35 years or older, male, living with friends or others, introduced to club drug use by non-regular sex partners, using methamphetamine recently, self-identified as gay/lesbian or bisexual, had sexual debut before 20 years old, and recently had sex under the influence of drugs. Having unprotected sex with non-regular partners in the past 30 days was associated with lower education levels, having sex to obtain drugs, and lower levels of HIV/AIDS knowledge. Club drug users should be targeted for intervention programs. Future research needs to identify other protective and risk factors for sexual risk behaviors and design interventions to reduce club drug use and associated sexual risk behaviors.

Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR = 1.14, 95% CI: 0.99–1.32) and CVD mortality (HR = 1.10, 95% CI: 0.86–1.41). However, NAFLD was associated with an increased risk of prevalent (OR = 1.81, 95% CI: 1.23–2.66) and incident (HR = 1.37, 95% CI: 1.10–1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR = 1.87, 95% CI: 1.47–2.37) and incident (HR = 2.31, 95% CI: 1.46–3.65) coronary artery disease (CAD), prevalent (OR = 1.24, 95% CI: 1.14–1.36) and incident (HR = 1.16, 95% CI: 1.06–1.27) hypertension, and prevalent (OR = 1.32, 95% CI: 1.07–1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD.