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简介：AbstractBackground:Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma.Methods:A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables.Results:The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014).Conclusions:Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.

简介：AbstractBackground:China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D).Methods:Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay.Results:A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 μg/L (0.60-3.42) for men and 1.40 μg/L (0.52-3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: -0.697 to -0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men.Conclusions:BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.

简介：AbstractBackground:Vitamin D deficiency has been reported to be associated with diabetic microvascular complications, but previous studies have only focused on the relationship between vitamin D and specific complications. Therefore, we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general, including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN).Methods:This was a cross-sectional study of 815 patients with type 2 diabetes mellitus (T2DM). Clinical information and laboratory results were collected from the medical records. The relationship between vitamin D and the three diabetic microvascular complications was investigated.Results:The serum 25-hydroxyvitamin D (25 [OH] D) level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications (P < 0.01). Univariate analysis showed that the 25 (OH) D level was related to DPN and DN, but not DR. After adjustment, the 25 (OH) D level was confirmed to be an independent protective factor for DPN (odds ratio [OR]: 0.968, P = 0.004]) and DN (OR: 0.962, P = 0.006). The prevalence of DPN and DN increased significantly as the serum 25 (OH) D levels decreased. Furthermore, patients with both DPN and DN had the lowest concentration of serum 25 (OH) D (P < 0.001), and the prevalence of macroalbuminuria increased more abruptly than that of microalbuminuria across the 25 (OH) D tertiles. Among the patients with vitamin D insufficiency, those with DPN presented more comorbid macroalbuminuria than those without DPN (15.32% vs. 4.91%; P = 0.001).Conclusions:Vitamin D deficiency is independently associated with higher risk of DPN and DN, but not DR, in T2DM patients. Further, it may be a potential predictor for both the occurrence and severity of DPN and DN.

简介：AbstractImportance:Pediatric palliative care (PPC) is an interdisciplinary collaboration that focuses on the prevention and relief of patient suffering. PPC has emerged as a critical field of medical expertise and practice. However, no information is available regarding the progress of PPC in the Chinese mainland.Objective:This study investigated the geographic distribution, team structure, and services of PPC teams in the Chinese mainland. It also investigated the level of understanding and implementation among pediatric oncologists regarding PPC.Methods:The PPC subspecialty group of the Pediatrics Society of the Chinese Medical Association included 45 PPC teams. The team structure and services were investigated using questionnaires mailed to the team leader of each PPC team. In addition, we sent questionnaires regarding the level of PPC understanding and implementation of PPC practices to 170 pediatric oncologists in 11 hospitals.Results:The geographical distribution of PPC teams is uneven in China. Most PPC teams are concentrated in the eastern provincial capital of China. Most PPC teams had limited staff and services. The level of PPC understanding was considerably limited across all demographics; most pediatric oncologists reported "some understanding" (n =71, 41.8%) or "poor understanding" (n = 50, 29.4%). Only 62.9% of pediatric oncologists had experience providing advice to family members regarding PPC matters.Interpretation:China is currently experiencing a critical shortage of PPC resources. Most pediatric oncologists had a limited understanding of PPC and reported limited practical implementation of PPC, which leads to underutilization of PPC resources.

简介：AbstractBackground:Our aim was to evaluate the sensitivity and specificity of the automated computer-based Alberta Stroke Program Early CT Score (e-ASPECTS) for acute stroke patients and compare the result with physicians at different levels.Methods:In our center, e-ASPECTS and 9 physicians at different levels retrospectively and blindly assessed baseline computed tomography (CT) images of 55 patients. Sensitivity, specificity, receiver-operating characteristic curves, Bland-Altman plots with mean score error, and Matthews correlation coefficients were calculated. Comparisons were made between the scores by physicians and e-ASPECTS with diffusion-weighted imaging (DWI) being the ground truth. Two methods for clustered data were used to estimate sensitivity and specificity in the region-based analysis.Results:In total, 1100 (55 patients × 20 regions per patient) ASPECTS regions were scored. In the region-based analysis, sensitivity of e-ASPECTS was better than junior doctors and residents (0.576 vs 0.165 and 0.111, p < 0.05) but inferior to senior doctors (0.576 vs 0.617). Specificity was lower than junior doctors and residents (0.883 vs 0.971 and 0.914) but higher than senior doctors (0.883 vs 0.809, p < 0.05). E-ASPECTS had the best Matthews correlation coefficient of 0.529, compared to senior doctors, junior doctors, and residents (0.463, 0.251, and 0.087, respectively).Conclusions:e-ASPECTS showed a similar performance to that of senior physicians in the assessment of brain CT of acute ischemic stroke patients with the Alberta Stroke Program Early CT score method.

简介：AbstractObjective:To identify potential early diagnostic markers for hepatitis B progression to primary liver carcinoma using routine immunological tests based on 6 cytokine combinations.Methods:Eight hundred and ninety-nine patients with hepatitis B progressing to early primary liver carcinoma admitted to and treated at Changhai Hospital, Naval Military Medical University, Shanghai, China between March 2015 and June 2017 were included in this observational study, including 666 patients with HBsAg+, HBeAb+, HBcAb+ liver carcinoma and 233 patients with HBsAg+, HBeAg+, HBcAb+ liver carcinoma. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of the different cytokine in the diagnosis of hepatocellular carcinoma in patients with hepatitis B. This study was approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China (approval No. CHEC2020-080) on June 6, 2020.Results:Changed levels of interleukin (IL)-1β, IL-2R, IL-8, and tumor necrosis factor (TNF)-α were statistically significant (P < 0.05). The area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, and Youden index for the diagnosis of primary liver carcinoma using the combination of IL-1β, IL-2R, IL-8, and TNF-α were 0.938, 79.2%, 96.7%, 96%, 82.0%, 0.759, respectively. The serum alpha-fetoprotein level in patients with primary liver carcinoma was positively correlated with IL-2R (r=0.3502, P < 0.001), IL-8 (r=0.1558, P=0.0273), and TNF-α (r=0.2544, P < 0.001) levels. The equation fitted to the results was logit(P)=0.086+ 0.01 × IL-2R-0.001 × IL-8-0.033 × TNF-α-0.041 × IL-1β.Conclusion:Our study establishes a novel, potentially valuable diagnostic model based on four cytokines related to the early stages of liver carcinoma.

简介：AbstractBackground:Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement.Methods:A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People’s Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student’s t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test.Results:The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t=-5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = -2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = -1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = -3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t= -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05).Conclusion:EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.

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简介：AbstractImportance:Patients with atopic dermatitis (AD) display compromised epidermal barrier and suffer from poor quality of life. We hypothesized that quality of life could reflect in the changes in the epidermal barrier function.Objective:To determine whether the epidermal barrier function correlates with the severity of pruritus and/or life quality in children with AD.Methods:A total of 120 children, aged 0-12 years, with moderate AD were enrolled. Children were topically treated with topical corticosteroids (TCS) and an emollient for 2 weeks. The Eczema Area and Severity Index (EASI), visual analogue scale (VAS) for pruritus severity, the Infant’s Dermatitis Quality of Life Index (IDQOL) and the Children’s Dermatology Life Quality Index (CDLQI) were evaluated. Transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration, and skin surface pH were measured. Correlations of epidermal barrier function with pruritus, life quality, and EASI were determined.Results:Following 2-week treatments, significant improvements were observed in EASI, TEWL, SC hydration, the VAS of pruritus, as well as DQOL (P < 0.001 for all). TEWL positively, while SC hydration negatively correlated with VAS pruritus, DQOL, and EASI (P < 0.001).Interpretation:Both TEWL and SC hydration levels can serve as indicators of the severity of pruritus and quality of life in children with AD.

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简介：AbstractObjective:To investigate the effects of rosmarinic acid (RA) on the DNA integrity and methylation levels of the H19 differentially methylated region (DMR) of freeze-dried human sperm after 1 week and 6 months of storage at 4℃.Methods:Semen samples from 15 healthy normospermic donors were used in this study. The samples were divided into five groups, including the control group with fresh sperm and four experimental groups with freeze-dried sperm (1-week storage with EGTA buffer solution, Group A; 1-week storage with EGTA buffer solution containing 105 μmol/L RA, Group B; 6-month storage with EGTA buffer solution, Group C; and 6-month storage with EGTA buffer solution containing 105 μmol/L RA, Group D). DNA integrity was evaluated using the sperm chromatin dispersion test. H19 DMR methylation levels were detected by bisulfite sequencing polymerase chain reaction.Results:After 1 week of storage, no differences in sperm DNA integrity were observed among Groups A, B, and controls (P > 0.05). After 6 months of storage, the sperm DNA integrity of Group D did not change significantly compared with that of the control group (P > 0.05), whereas that of Group C decreased significantly (P < 0.05). There were no differences in H19 DMR methylation levels among the five groups (P > 0.05).Conclusions:The DNA integrity of freeze-dried human sperm can be effectively protected by adding RA within 6 months, and the H19 DMR methylation level of human sperm can be maintained for 6 months after freeze-drying.