Background: Medical care workers experienced unprecedented levels of workload and pressure since the outbreak of coronavirus disease 2019 (COVID-19). Little is known about its exact impact on medical care workers and related factors in China. This study aims to identify the psychological impact of COVID-19 on medical care workers in China. Methods: From February 23 to March 5, 2020, a cross-sectional survey was conducted among 863 medical care workers from seven provinces in China using standard questionnaires measuring adverse psychological outcomes including Impact of Event Scale-6 (IES-6), Depression, Anxiety and Stress Scale(DASS)and related psychosocial factors like perceived threat, social support and coping strategies. Exploratory Factor analysis was performed to identify the dimensions of perceived threat by study participants. Multivariate regression was used to examine the determinants of adverse psychological outcomes. Results: Posttraumatic stress (PTS) were prevalent in this sample of health care professionals, and 40.2% indicated positive screens for significant posttraumatic stress disorder symptoms. The proportion of having mild to extremely severe symptoms of depression, anxiety and stress were 13.6, 13.9 and 8.6%, respectively. Perceived threat and passive coping strategies were positively correlated to PTS and DASS scores, while perceived social support and active coping strategies were negatively correlated to DASS scores. Nurses were more likely to be anxious than others among medical care workers during the COVID-19 epidemic. Conclusions: Adverse psychological symptoms were prevalent among medical care workers in China during the COVID-19 epidemic. Screening for adverse psychological outcomes and developing corresponding preventive measures would be beneficial in decreasing negative psychological outcomes.

Background: Gemcitabine resistance (GR) is a significant clinical challenge in pancreatic adenocarcinoma (PAAD) treatment. Macrophages in the tumor immune-microenvironment are closely related to GR. Uncovering the macrophage-induced GR mechanism could help devise a novel strategy to improve gemcitabine treatment outcomes in PAAD. Therefore, preclinical models accurately replicating patient tumor properties are essential for cancer research and drug development. Patient-derived organoids (PDOs) represent a promising in vitro model for investigating tumor targets, accelerating drug development, and enabling personalized treatment strategies to improve patient outcomes. Methods: To investigate the effects of macrophage stimulation on GR, co-cultures were set up using PDOs from three PAAD patients with macrophages. To identify signaling factors between macrophages and pancreatic cancer cells (PCCs), a 97-target cytokine array and the TCGA-GTEx database were utilized. The analysis revealed CCL5 and AREG as potential candidates. The role of CCL5 in inducing GR was further investigated using clinical data and tumor sections obtained from 48 PAAD patients over three years, inhibitors, and short hairpin RNA (shRNA). Furthermore, single-cell sequencing data from the GEO database were analyzed to explore the crosstalk between PCCs and macrophages. To overcome GR, inhibitors targeting the macrophage-CCL5-Sp1-AREG feedback loop were evaluated in cell lines, PDOs, and orthotopic mouse models of pancreatic carcinoma. Results: The macrophage-CCL5-Sp1-AREG feedback loop between macrophages and PCCs is responsible for GR. Macrophage-derived CCL5 activates the CCR5/AKT/Sp1/CD44 axis to confer stemness and chemoresistance to PCCs. PCC-derived AREG promotes CCL5 secretion in macrophages through the Hippo-YAP pathway. By targeting the feedback loop, mithramycin improves the outcome of gemcitabine treatment in PAAD. The results from the PDO model were corroborated with cell lines, mouse models, and clinical data. Conclusions: Our study highlights that the PDO model is a superior choice for preclinical research and precision medicine. The macrophage-CCL5-Sp1-AREG feedback loop confers stemness to PCCs to facilitate gemcitabine resistance by activating the CCR5/AKT/SP1/CD44 pathway. The combination of gemcitabine and mithramycin shows potential as a therapeutic strategy for treating PAAD in cell lines, PDOs, and mouse models.

Background: Cost estimation is a central feature of health economic analyses. The aim of this study was to use a micro-costing approach and a societal perspective to estimate aggregated costs associated with cervical cancer screening, diagnosis and treatment in rural China.Methods: We assumed that future screening programs will be organized at a county level (population ~250,000), and related treatments will be performed at county or prefecture hospitals; therefore, this study was conducted in a county and a prefecture hospital in Shanxi during 2008–9. Direct medical costs were estimated by gathering information on quantities and prices of drugs, supplies, equipment and labour. Direct non-medical costs were estimated via structured patient interviews and expert opinion.Results: Under the base case assumption of a high-volume screening initiative (11,475 women screened annually per county), the aggregated direct medical costs of visual inspection, self-sampledcareHPV (Qiagen USA) screening, clinician-sampledcareHPV, colposcopy and biopsy were estimated as US$2.64,$7.49,$7.95,$3.90 and $5.76, respectively. Screening costs were robust to screening volume (<5% variation if 2,000 women screened annually), but costs of colposcopy/biopsy tripled at the lower volume. Direct medical costs of Loop Excision, Cold-Knife Conization and Simple and Radical Hysterectomy varied from $61–544, depending on the procedure and whether conducted at county or prefecture level. Direct non-medical expenditure varied from $0.68–$3.09 for screening/diagnosis and $83–$494 for pre-cancer/cancer treatment.Conclusions: Diagnostic costs were comparable to screening costs for high-volume screening but were greatly increased in lower-volume situations, which is a key consideration for the scale-up phase of new programs. The study’s findings will facilitate cost-effectiveness evaluation and budget planning for cervical cancer prevention initiatives in China.

Background: A new lower-cost rapid-throughput human papillomavirus (HPV) test (careHPV, Qiagen, Gaithersburg, USA) has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia.Methods: We assessed the outcomes and cost-effectiveness ofcareHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA) or in combination with Lugol's iodine (VIA/VILI). Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER) and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed.Results: For all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective); VIA/VILI;careHPV@1.0 pg/ml andcareHPV@0.5 pg/ml (most effective). For once-lifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA) to 12% (forcareHPV@0.5) over the long term, with a CER of US$557 (for VIA) to $959 (forcareHPV@1.0) per life year saved (LYS) compared to no intervention; referenced to a 2008 GDP per capita in Shanxi Province of $2,975. Correspondingly, regular screening with an age-standardised participation rate of 62% (which has been shown to be achievable in this setting) would reduce cervical cancer mortality by 19-28% (for 10-yearly screening) to 43-54% (using IARC-recommended intervals), with corresponding CERs ranging from $665 (for 10-yearly VIA) to $2,269 (for IARC-recommended intervals usingcareHPV@1.0) per LYS.Conclusions: This modelled analysis suggests that primarycareHPV screening compares favourably to visual inspection screening methodologies in rural China, particularly if used as part of a regular screening program.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare neuroendocrine tumors, and lack of data in Asian populations especially in China. The aim of this retrospective study was to assess the clinical, pathological and prognostic characteristics of GEP-NENs in China.

Plasma markers have been continuously advocated as pointers to estimate the long-term risk of cardiovascular disease in the general population. We examined the relationship between plasma high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), high-sensitivity cardiac troponin T (hs-cTnT), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 25-Hydroxyvitamin D (25OHD), glycosylated hemoglobin A1c (HbA1c), and serum uric acid (SUA) levels and hypertension in middle and old aged population. A total of 2624 Chinese (62.02 ± 5.73 years old) were recruited into a population-based, cross-sectional study. Plasma hs-CRP, Hcy, HbA1c, and SUA levels were significantly higher in the hypertension group compared with control in the entire population and men (P = 0.05 for all). We observed a positive association between the highest quartiles of Hcy, NT-proBNP, HBA1c concentrations, and the prevalence of hypertension, OR (95% CI) = 1.48 (1.16–1.90), 1.62 (1.27–2.07) and 1.94 (1.49–2.52), respectively. The multivariable-adjusted OR of hypertension for the fourth versus the first quartile of homocysteine were 2.00 and 1.39 in men and women, respectively. In conclusion, our study found an independent and robust association between elevated Hcy, NT-ProBNP, and HBA1c levels and prevalence of hypertension in the middle-aged and elderly Chinese population. A follow-up study is necessary to endorse the observed association.