A vascularized model of the human liver mimics regenerative responses.

Liver regeneration is a well-orchestrated process that is typically studied in animal models. Although previous animal studies have offered many insights into liver regeneration, human biology is less well understood. To this end, we developed a three-dimensional (3D) platform called structurally vascularized hepatic ensembles for analyzing regeneration (SHEAR) to model multiple aspects of human liver regeneration. SHEAR enables control over hemodynamic alterations to mimic those that occur during liver injury and regeneration and supports the administration of biochemical inputs such as cytokines and paracrine interactions with endothelial cells. We found that exposing the endothelium-lined channel to fluid flow led to increased secretion of regeneration-associated factors. Stimulation with relevant cytokines not only amplified the secretory response, but also induced cell-cycle entry of primary human hepatocytes (PHHs) embedded within the device. Further, we identified endothelial-derived mediators that are sufficient to initiate proliferation of PHHs in this context. Collectively, the data presented here underscore the importance of multicellular models that can recapitulate high-level tissue functions and demonstrate that the SHEAR device can be used to discover and validate conditions that promote human liver regeneration.

Targeting glutamine metabolism exhibits anti-tumor effects in thyroid cancer.

BACKGROUND: Effective treatment for patients with advanced thyroid cancer is lacking. Metabolism reprogramming is required for cancer to undergo oncogenic transformation and rapid tumorigenic growth. Glutamine is frequently used by cancer cells for active bioenergetic and biosynthetic needs. This study aims to investigate whether targeting glutamine metabolism is a promising therapeutic strategy for thyroid cancer. METHODS: The expression of glutaminase (GLS) and glutamate dehydrogenase (GDH) in thyroid cancer tissues was evaluated by immunohistochemistry, and glutamine metabolism-related genes were assessed using real time-qPCR and western blotting. The effects of glutamine metabolism inhibitor 6-diazo-5-oxo-l-norleucine (DON) on thyroid cancer cells were determined by CCK-8, clone formation assay, Edu incorporation assay, flow cytometry, and Transwell assay. The mechanistic study was performed by real time-qPCR, western blotting, Seahorse assay, and gas chromatography-mass spectrometer assay. The effect of DON prodrug (JHU-083) on thyroid cancer in vivo was assessed using xenograft tumor models in BALB/c nude mice. RESULTS: GLS and GDH were over-expressed in thyroid cancer tissues, and GLS expression was positively associated with lymph-node metastasis and TNM stage. The growth of thyroid cancer cells was significantly inhibited when cultured in glutamine-free medium. Targeting glutamine metabolism with DON inhibited the proliferation of thyroid cancer cells. DON treatment did not promote apoptosis, but increased the proportion of cells in the S phase, accompanied by the decreased expression of cyclin-dependent kinase 2 and cyclin A. DON treatment also significantly inhibited the migration and invasion of thyroid cancer cells by reducing the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Non-essential amino acids, including proline, alanine, aspartate, asparagine, and glycine, were reduced in thyroid cancer cells treated with DON, which could explain the decrease of proteins involved in migration, invasion, and cell cycle. The efficacy and safety of DON prodrug (JHU-083) for thyroid cancer treatment were verified in a mouse model. In addition to suppressing the proliferation and metastasis potential of thyroid cancer in vivo, enhanced innate immune response was also observed in JHU-083-treated xenograft tumors as a result of decreased expression of cluster of differentiation 47 and programmed cell death ligand 1. CONCLUSIONS: Thyroid cancer exhibited enhanced glutamine metabolism, as evidenced by the glutamine dependence of thyroid cancer cells and high expression of multiple glutamine metabolism-related genes. Targeting glutamine metabolism with DON prodrug could be a promising therapeutic option for advanced thyroid cancer.

[The ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion].

Objective: The present retrospective study aimed to analyses the ventilation efficacy and safety of new nasopharyngeal airway applied in left atrial appendage occlusion. Methods: A total of 37 advanced aged patients diagnosed with atrial fibrillation(>65 years)who underwent left atrial appendage occlusion (LAAO) in Xuanwu Hospital of Capital Medical University from March 2021 to March 2022 were enrolled in this study. All patients received supplemental oxygen by a new nasopharyngeal airway to ensure intraoperative ventilation. The primary outcome was the occurrence of hypoxemia. The secondary outcomes included the incidence of hypotension after anesthesia, the incidence of body movement during surgery, significant fluctuations of the vital signs such as mean arterial pressure (MAP), heart rate (HR), saturation of pulse oxygen (SpO2) and respiratory rate (RR) at different time points (T1: pre-operation; T2: at the time of placing nasopharyngeal airway; T3: at the time of placing transesophageal echocardiography(TEE); T4: at the time of TEE intraoperative exploration; T5: end of the surgery; T6: at the time of patient woke up), and the incidence of postoperative adverse events. Results: There were 24 males and 13 females with a mean age of (73.8±7.7) years. The incidence of hypoxemia was 16.2% (6/37), which could return to normal after simple treatment. The incidence of hypotension was 27.0% (10/37), occurred after anesthesia induction mainly.32.4% (12/37) of the patients experienced movements, but no adverse events led to surgical termination. MAP at different time points was significantly different (P=0.001), but other vital signs of HR, SpO2 and RR were not significantly different(all P>0.05), without serious hemodynamic fluctuations. The incidence of postoperative adverse cardiovascular events was 10.8% (4/37), and delirium was 2.7% (1/37). All patients successfully completed the surgery and were safely discharged from the hospital. Conclusion: The new nasopharyngeal airway can meet the requirements of airway management during left atrial appendage occlusion under intravenous anesthesia without serious adverse events.

[Correlation of 1p/16q loss of heterozygosity and 1p gain with clinicopathological characteristics and prognosis in Wilms tumor].

Objective: To investigate the relationship between 1p/16q loss of heterozygosity (LOH) and 1p gain in Wilms tumor and their clinicopathologic characteristics and prognosis. Methods: A total of 175 Wilms tumor samples received from the Department of Pathology, Beijing Children's Hospital from September 2019 to August 2022 were retrospectively analyzed. The histopathologic type and presence of lymph node involvement were evaluated by two pathologists. The clinical data including patients'gender, age, tumor location, preoperative chemotherapy, and tumor stage were summarized. Fluorescence in situ hybridization (FISH) was done to detect 1p/16q LOH and 1p gain and their correlation with the clinicopathological features and prognosis were analyzed. Results: Among the 175 samples, 86 cases (49.1%) were male and 89 (50.9%) were female. The mean age was (3.5±2.9) years, and the median age was 2.6 years. There were 26 (14.9%) cases with 1p LOH, 28 (16.0%) cases with 16q LOH, 10 (5.7%) cases of LOH at both 1p and 16q, and 53 (30.3%) cases with 1q gain. 1q gain was significantly associated with 1p LOH (P<0.01) and 16q LOH (P<0.01). There were significant differences (P<0.01) between 1q gain, 1p LOH and 16q LOH among different age groups. The rate of 16q LOH in the high-risk histopathological subtype (50.0%) was significantly higher than that in the intermediate-risk subtype (13.6%, P<0.05). The frequency of 1q gain, 1p LOH, and 16q LOH in children with advanced clinical stages (Ⅲ and Ⅳ) was significantly higher than that in children with early clinical stages (Ⅰ and Ⅱ). 1q gain, 1p LOH, and 16q LOH showed no significant correlation with gender, unilateral or bilateral disease, chemotherapy, or lymph node metastasis. The progression-free survival (PFS) time for patients with 1q gain and 1p LOH was significantly shorter than those without these aberrations (P<0.05). Additionally, the PFS time of patients with 16q LOH was slightly shorter than those with normal 16q, although the difference was not statistically significant. Patients with stage Ⅲ to Ⅳ disease exhibiting 1q gain or 1p LOH had a significantly higher relative risk of recurrence, metastasis, and mortality. Conclusions: 1p/16q LOH and 1q gain are associated with age, high-risk histological type, and clinical stage in Wilms tumor. 1q gain and 1p LOH are significantly correlated with the prognosis of Wilms tumor.

Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population.

AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

Comparison of aroma properties of infant formulas: Differences in key aroma compounds and their possible origins in processing.

Aroma is an important attribute of infant formula (IF). In this study, 218 volatiles and 62 odor-active compounds were detected from IF by dynamic headspace sampling combined with comprehensive 2-dimensional gas chromatography-olfactometry-mass spectrometry. Aldehydes and ketones were determined as the most abundant odor-active compounds. Among them, the contents of pentanal and hexanal were the most abundant, while 1-octen-3-one had the highest flavor dilution factor and odor activity value in most of the IF. Sensory evaluation and electronic nose analysis showed that the skimming process, the fatty acid composition, and powdered or liquid milk base used for the production of IF may be important factors resulting in their differences in aroma profiles and compounds. These differences were assumed to be mainly ascribed to the Maillard reaction and lipid oxidation, which were largely influenced by the temperature and water activity.

[Effects of adjuvant trastuzumab on long-term survival of T1N0M0 stage human epidermal growth factor receptor 2 positive breast cancer: a real-world study].

Objective: To investigate the prognosis impact of adjuvant trastuzumab treatment on human epidermal growth factor receptor 2 (HER-2) positive early breast cancer patients. Methods: A retrospective study was conducted, HER-2-positive T1N0M0 stage breast cancer patients who underwent surgery in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2010 to December 2019 were divided into treatment group and control group according to whether they were treated with trastuzumab or not. Propensity score matching (PSM) was used to balance the confounding bias caused by differences in baseline characteristics between the two groups. Cox proportional hazards model was used to analyze the risk factors affecting disease-free survival (DFS). The Kaplan-Meier method was used to estimate the 3- and 5-year DFS and overall survival (OS) rates of the two groups before and after PSM. Results: There were 291 patients with HER-2 positive T1N0M0 stage breast cancer, including 21 cases in T1a (7.2%), 61 cases in T1b (21.0%), and 209 cases in T1c (71.8%). Before PSM, there were 132 cases in the treatment group and 159 cases in the control group, the 5-year DFS rate was 88.5%, and the 5-year OS rate was 91.5%. After PSM, there were 103 cases in the treatment group and 103 cases in the control group, the 5-year DFS rate was 86.0%, and the 5-year OS rate was 88.5%. Before PSM, there were significant differences in tumor size, histological grade, vascular invasion, Ki-67 index, postoperative chemotherapy or not and radiotherapy between the treatment group and the control group (P<0.05). After PSM, there were no significant difference in clinicopathological features between the treatment group and the control group (P>0.05). Multivariate analysis showed that histological grade (HR=2.927, 95 CI: 1.476, 5.805; P=0.002), vascular invasion (HR=3.410, 95 CI: 1.170, 9.940; P=0.025), menstrual status (HR=3.692, 95 CI: 1.021, 13.344, P=0.046), and chemotherapy (HR=0.238, 95 CI: 0.079, 0.720; P=0.011) were independent factors affecting DFS. After PSM, the 5-year DFS rate of the treatment group was 89.2%, while that of the control group was 83.5%(P=0.237). The 5-year OS rate of the treatment group was 96.1%, while that of the control group was 84.7%(P=0.036). Conclusion: Postoperative targeted therapy with trastuzumab can reduce the risk of recurrence and metastasis in patients with HER-2-positive T1N0M0 stage breast cancer.

Reactive cutaneous capillary endothelial proliferation predicted the efficacy of camrelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma.

BACKGROUND: Reactive cutaneous capillary endothelial proliferation (RCCEP), a special adverse event (AE) only observed in patients treated with camrelizumab, was reported to be correlated with the efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. This study to analyze the possible correlation between the occurrence of RCCEP and efficacy of camrelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). MATERIAL AND METHODS: In this study, we retrospectively analyzed the efficacy and RCCEP occurrence of camrelizumab in 58 patients with R/M HNSCC in the Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University School of Medicine between January 2019 and June 2022. Kaplan-Meier analysis was used to assess the correlation between the occurrence of RCCEP and the survival of enrolled patients, and COX multifactor analysis was adopted to evaluate associated factors that affected the efficacy of camrelizumab immunotherapy. RESULTS: A significant correlation between the incidence of RCCEP and a higher objective response rate was observed in this study (p=0.008). The occurrence of RCCEP was associated with better median overall survival (17.0 months vs. 8.7 months, p<0.0001, HR=5.944, 95% CI:2.097-16.84) and better median progression-free survival (15.1 months vs. 4.0 months, p<0.0001, HR=4.329,95% CI:1.683-11.13). In COX multifactor analysis, RCCEP occurrence was also an independent prognostic factor affecting OS and PFS in patients with R/M HNSCC. CONCLUSIONS: The occurrence of RCCEP can show a better prognosis, it could be used as a clinical biomarker to predict the efficacy of camrelizumab treatment.

[Pre-operative prognostic nutritional index as a predictive factor for prognosis in non-metastatic renal cell carcinoma treated with surgery].

OBJECTIVE: To evaluate the implications of the prognostic nutrition index (PNI) in non-metastatic renal cell carcinoma (RCC) patients treated with surgery and to compare it with other hematological biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII). METHODS: A cohort of 328 non-metastatic RCC patients who received surgical treatment between 2010 and 2012 at Peking University First Hospital was analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of the hematological biomarkers. The Youden index was maximum for PNI was value of 47.3. So we divided the patients into two groups (PNI≤ 47. 3 and >47. 3) for further analysis. Categorical variables [age, gender, body mass index (BMI), surgery type, histological subtype, necrosis, pathological T stage and tumor grade] were compared using the Chi-square test and Student' s t test. The association of the biomarkers with overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model. RESULTS: According to the maximum Youden index of ROC curve, the best cut-off value of PNI is 47. 3. Low level of PNI was significantly associated with older age, lower BMI and higher tumor pathological T stage (P < 0.05). Kaplan-Meier univariate analysis showed that lower PNI was significantly correlated with poor OS and DFS (P < 0.05). In addition, older age, lower BMI, tumor necrosis, higher tumor pathological T stage and Fuhrman grade were significantly correlated with poor OS (P < 0.05). Cox multivariate analysis showed that among the four hematological indexes, only PNI was an independent factor significantly associated with OS, whether as a continuous variable (HR=0.9, 95%CI=0.828-0.978, P=0.013) or a classified variable (HR=2.397, 95%CI=1.061-5.418, P=0.036). CONCLUSION: Low PNI was a significant predictor for advanced pathological T stage, decreased OS, or DFS in non-metastatic RCC patients treated with surgery. In addition, PNI was superior to the other hematological biomar-kers as a useful tool for predicting prognosis of RCC in our study. It should be externally validated in future research before the PNI can be used widely as a predictor of RCC patients undergoing nephrectomy.

[Genetic mutation profiles for children with congenital hypothyroidism in Fujian province].

Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.

[A pre-conception cohort study of fertility and its related factors among couples with the intention of conception].

Objective: To describe fertility and explore factors associated with it among pre-conception couples of childbearing age. Methods: Based on the pre-conceptional offspring trajectory study of the School of Public Health of Fudan University, couples of childbearing age who participated in the pre-conception physical examination in Shanghai Jiading District from 2016 to 2021 were recruited and followed up. Couples' time to pregnancy (TTP) was analyzed and Cox proportional hazards regression model was used to explore the factors associated with TTP. Kaplan-Meier was used to calculate each menstrual cycle's cumulative pregnancy rate. Results: A total of 1 095 preconception couples were included in the analysis, the M(Q1,Q3)of TTP was 4.33 (2.41, 9.78) menstrual cycles. Age of women (FR=0.90, 95%CI: 0.85-0.95, P<0.001), women who were overweight or obese before pregnancy (FR=0.36, 95%CI: 0.24-0.55, P<0.001), women who were exposed to second-hand smoking (FR=0.63, 95%CI: 0.44-0.92, P=0.016), women whose home or office had been renovated in the past 2 years and had a particular smell (FR=0.46, 95%CI: 0.26-0.81, P=0.008) were risk factors for impaired fertility. Regular menstrual cycles (FR=1.64, 95%CI: 1.16-2.31, P=0.005), females who often drank tea/coffee (FR=1.55, 95%CI: 1.11-2.17, P=0.011) and males who took folic acid before conception (FR=2.35, 95%CI: 1.38-4.23, P=0.002) were associated with better fertility. The cumulative pregnancy rate of 3, 6, and 12 menstrual cycles was 37.6%, 64.4%, and 78.4%, respectively. Conclusion: Older couples, overweight or obesity before pregnancy, irregular menstruation, exposure to secondhand smoke and decoration pollutants in females are associated with impaired fertility. Frequent tea/coffee drinking before pregnancy in females and taking folic acid before pregnancy in males are associated with shortened conception time.

[Association of hs-CRP with frailty and its components among the elderly over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.

[Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years].

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) µg/L, 19.36 (16.92, 22.15) µg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

[Application value of serum protein indicators in constructing the early prediction model for the prognosis of patients with pulmonary tuberculosis].

Objective: To analyze the clinical significance of laboratory examination indicators as the key prognostic factors and to construct an early prediction model for prognosis assessment of pulmonary tuberculosis patients. Methods: The basic information, biochemical indexes and blood routine items of 163 tuberculosis patients (144 males and 19 females, aged 41-70 years, with an average age of 56 years) and 118 healthy persons who underwent physical examination (101 males and 17 females, aged 46-64 years, with an average age of 54 years) in Suzhou Fifth People's Hospital from January 2012 to December 2020 were retrospectively collected. According to the presence of Mycobacterium tuberculosis after six months of treatment, the enrolled patients were divided into a cured group (96 cases) and a treatment failure group (67 cases). To analyze the baseline levels of laboratory examination indicators between these two groups, we screened the key predictors and the binary logistic regression method in SPSS statistics software was used to construct the prediction model. Results: The baseline levels of total protein, albumin, prealbumin, glutamic-pyruvic transaminase, erythrocyte, hemoglobin and lymphocyte were significantly higher in the cured group than in the treatment failure group. After 6 months of treatment, the indexes of total protein, albumin and prealbumin increased significantly in the cured group, but remained at the low levels in the treatment failure group. Receiver operating characteristic (ROC) curve analysis showed that total protein, albumin and prealbumin as independent predictors for forecasting the prognosis of pulmonary tuberculosis patients had the highest prediction accuracy. Logistic regression analysis showed that the combination of these three key predictors could construct the best early prediction model for assessing the prognosis of pulmonary tuberculosis patients, with a prediction accuracy of 0.924 (0.886-0.961), sensitivity of 75.0%, specificity of 94%, showing an ideal prediction accuracy. Conclusions: The routine test indexes of total protein, albumin and prealbumin show good application value in the construction of early prediction model for prognosis evaluation of pulmonary tuberculosis treatment. The combined prediction model consisting of total protein, albumin and prealbumin is expected to provide a theoretical basis and reference model for precision treatment and prognosis assessment of tuberculosis patients.

[Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis].

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

Physical activity patterns, genetic susceptibility, and risk of hip/knee osteoarthritis: a prospective cohort study based on the UK Biobank.

OBJECTIVES: The effect of physical activity on hip/knee osteoarthritis (OA) and how it varies by genetic susceptibility to OA remains inconclusive. METHODS: In a cohort study of UK Biobank, 436,166 OA-free participants were recruited in 2006-2010 and followed for knee/hip OA until the end of 2020. 28 physical activity-related items were collected at baseline. Cox regression was used to estimate associations between physical activity behaviors, as well as major activity patterns (i.e., significant principal components[PCs] identified by principal component analysis), and risk of OA, adjusting for multiple confounders. We further stratified the analyses by polygenic risk score (PRS) for OA to examine the impact of genetic susceptibility to OA on the studied association. RESULTS: During a mean follow-up of 11.15 years, 13,227 hip and 21,119 knee OA cases were identified. 19, out of 28, studied items showed associations with increased OA risk. Compared with low adherence group(<1st tertile of PC score for each pattern), individuals with high adherence to five identified patterns were associated with increased risk of OA. The moderate adherence to "strenuous sports"(HR = 0.93, 95%CI: 0.89-0.97) and "walking for pleasure"(HR = 0.93, 95%CI: 0.89-0.98) patterns was associated with reduced OA. Similar risk patterns were obtained in the stratified analysis by PRS levels for OA. CONCLUSION: High intensity of most activity patterns were associated with increased OA. However, a protective effect was suggested for moderate adherence to patterns of "strenuous sports" and "walking for pleasure" that consistent across different genetic susceptibilities, underscoring the potential benefits of moderate-intensity physical activity on OA.

Homogeneous, Micron-Scale High-Energy-Density Matter Generated by Relativistic Laser-Solid Interactions.

Short-pulse, laser-solid interactions provide a unique platform for studying complex high-energy-density matter. We present the first demonstration of solid-density, micron-scale keV plasmas uniformly heated by a high-contrast, 400 nm wavelength laser at intensities up to 2×10^{21} W/cm^{2}. High-resolution spectral analysis of x-ray emission reveals uniform heating up to 3.0 keV over 1 µm depths. Particle-in-cell simulations indicate the production of a uniformly heated keV plasma to depths of 2 µm. The significant bulk heating and presence of highly ionized ions deep within the target are attributed to the few MeV hot electrons that become trapped and undergo refluxing within the target sheath fields. These conditions enabled the differentiation of atomic physics models of ionization potential depression in high-energy-density environments.

Feasibility of an ultra-low dose contrast media protocol for coronary CT angiography.

AIM: To evaluate the feasibility of an ultra-low volume contrast media (CM) protocol for coronary computed tomography angiography (CTA). MATERIALS AND METHODS: In total, 214 patients receiving coronary CTA were enrolled prospectively and divided into group A (n=107) receiving a conventional dose of CM and group B (n=107) receiving an ultra-low dose. CT values of the right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX) were measured and radiation doses recorded. The image quality was compared between the groups. Changes in renal function indices and proteinuria before, 24, and 72 hours after coronary CTA among those with chronic kidney disease (CKD) were also assessed. RESULTS: There were significant differences in CT values and radiation doses between groups A and B. In group A, the average RCA, LAD, and LCX CT values were 412.5 ± 79.2, 423.5 ± 73.7, and 422.0 ± 88.1 HU, respectively. In group B, the average RCA, LAD, and LCX CT values were 275.2 ± 16.2, 277.8 ± 16.4, and 278.9 ± 16.5 HU, respectively. The radiation dose in the ultra-low protocol recipients (118.70 ± 18.52 mGy·cm) was significantly lower than that used in conventional coronary CTA (131.75 ± 20.96 mGy·cm). The image quality of group B was comparable to that of group A, satisfying the diagnostic requirement. In patients with mild CKD, there were no significant differences in renal functions after coronary CTA. CONCLUSION: An ultra-low CM protocol was established for coronary CTA, providing comparable image quality and diagnostic yields but significantly lower radiation dose compared with a conventional protocol. This new protocol might be applicable to patients with mild CKD.

Investigation of the motor skills assessments of typically developing preschool children in China.

BACKGROUND: The assessment of preschoolers' motor skills is essential to know young children's motor development and evaluate the intervention effects of promotion in children's sports activities. The purpose of this study was to review the motor skills assessment tools in Chinese pre-school-aged children, compare them in the international context, and provide guidelines to find appropriate motor skill assessment tools for developing children in China. METHODS: A comprehensive literature search was carried out using the WANFAGN, CNKI, VIP, ERIC, EMBASE, MEDLINE, and SPORT Discus databases. Relevant articles published between January 2000 and May 2020 were retrieved. Studies that described the discriminative and evaluative measures of motor skills among the population aged 3-6 years in China were included. RESULTS: A total of 17 studies were included in this study describing seven tools, including four self-developed tools and three international tools used in China. TGMD-2 appeared in a large proportion of the studies. The international tools used in China were incomplete in terms of translation, verification of reliability and validity, item selection, and implementation. Regarding the self-constructed tools, the CDCC was the most utilized self-developed tool, but it was mainly applied in intellectual development assessment. By comparing Chinese self-constructed and international tools, the construction of the CDCC and the Gross Motor Development Assessment Scale contained relatively complete development steps. However, the test content, validity and reliability, implementation instruction, and generalizability of self-constructed tools are still lacking. CONCLUSIONS: Both international and self-developed motor skills assessment tools have been rarely applied in China. Available tools lack enough validation and appropriate adjustments. Cultural differences in motor development between Chinese and Western populations should be considered when constructing a Chinese localized motor skill assessment tool.