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Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively explore the mechanisms underlying this age-related disparity, we conducted the integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, and elucidated six functionally and spatially distinctive macrophage groups and lymphocytes surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we characterized the dysfunction of Spp1+ macrophages in aged mice impeded the activation of the type Ⅱ immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As an important potential dust suppression method, the slow onset time is one of the key factors that restrict the effect of microbial dust suppressant. In the early stage, we have confirmed that extracellular polymeric substances (EPS) can improve the dust suppression effect by wetting coal dust and increasing Ca 2+ nucleation sites. Therefore, in this study, chitosan (CTS) and bovine serum albumin (BSA) in different ratios (CTS: BSA = 1:1, 1:2, 2:1) as model molecules of EPS were combined with Bacillus subtilis to prepare efficient and fast microbial dust suppressants. Furthermore, the interaction forces were analyzed through molecular dynamics simulation. Results showed that adding CTS and BSA would improve the dust suppression effect, and the dust suppression effect was the best when the ratio of CTS: BSA was 1:2. In addition, the contact angle decreased as the BSA content increased. The Fourier transform infrared spectroscopy (FTIR) results showed that when the ratio of CTS to BSA was 1:2, the dust suppressants were easier to interact with coal dust by the key functional groups and form calcite type CaCO 3 . The molecular dynamics simulation results showed that the main interaction was Van der Waals force. In addition, the interaction force was strongest when CTS: BSA was 1:2, increasing by 137% compared with the microbial dust suppressants without CTS or BSA. This study provides theoretical support for the development of efficient and rapid microbial dust suppressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Exposure to major life stressors and aberrant brain functioning have been linked to anxiety and depression, especially during periods of heighted functional brain plasticity, such as adolescence. However, it remains unclear if specific characteristics of major life stressors and functional network disruptions differentially predict anxiety and depression symptoms over time and, if so, whether they act independently or jointly., Methods: We collected baseline lifetime stressor exposure data and resting-state functional magnetic resonance imaging data in a longitudinal sample of 107 adolescents enriched for anxiety and depressive disorders. We examined five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at baseline, 6-month and 12-month follow-ups. Linear mixed effect models tested if these stressor characteristics, functional connectivity within and between frontoparietal, default, and ventral attention networks, and their interactions differentially predicted anxiety and depression symptoms at 6-month and 12-month follow-ups., Results: Greater lifetime severity of physical danger and humiliation prospectively predicted increased anxiety symptoms at both follow-ups, whereas greater lifetime entrapment severity prospectively predicted higher anxiety and depression symptoms. Only the effects of lifetime entrapment severity were robust to including within- and between-network functional connectivity metrics and other significantly predictive stressor characteristics. Lifetime entrapment severity more strongly predicted anxiety symptoms in youth with higher default network connectivity. Greater functional connectivity between frontoparietal and default networks prospectively predicted increased depression symptoms., Conclusions: Taken together, these results underscore the critical importance of using stressor characteristics and functional connectivity jointly to study predictors for adolescent anxiety and depression., Competing Interests: Disclosures The authors declare no conflicts of interest with respect to this work.

Cognitive control, the ability to adapt thoughts and actions to shifting contexts and goals, is composed primarily of three distinct yet interrelated components: Inhibition, Shifting, and Updating. While prior research has examined the nature of different cognitive components as well as their inter-relationships, fewer studies examined whole-brain connectivity to predict individual differences for the three cognitive components and associated tasks. Here, using the Connectome-based Predictive Modelling (CPM) approach and open-access data from the Human Connectome Project, we built brain network models to successfully predict individual performance differences on the Flanker task, the Dimensional Change Card Sort task, and the 2-Back task, each putatively corresponding to Inhibition, Shifting, and Updating. We focused on grayordinate fMRI data collected during the 2-Back tasks after confirming superior predictive performance over resting-state and volumetric data. High cross-task prediction accuracy as well as joint recruitment of canonical networks, such as the frontoparietal and default-mode networks, suggest the existence of a common cognitive control factor. To directly investigate the relationships among the three cognitive control components, we developed new measures to disentangle their shared and unique aspects. Our analysis confirmed that a shared control component can be well predicted from functional connectivity patterns densely located around the frontoparietal, default-mode and dorsal attention networks. In contrast, the Shifting-specific and Inhibition-specific components exhibited lower cross-prediction performance, indicating their distinct and specialized roles. Notably, the Updating-specific component showed significant cross-prediction with the general control factor, suggesting its central role in cognitive control. Given the limitation that individual behavioral measures do not purely reflect the intended cognitive constructs, our study demonstrates the need to distinguish between common and specific components of cognitive control.

Digital technology has emerged as a transformative tool in dental implantation, profoundly enhancing accuracy and effectiveness across multiple facets, such as diagnosis, preoperative treatment planning, surgical procedures, and restoration delivery. The multiple integration of radiographic data and intraoral data, sometimes with facial scan data or electronic facebow through virtual planning software, enables comprehensive 3-dimensional visualization of the hard and soft tissue and the position of future restoration, resulting in heightened diagnostic precision. In virtual surgery design, the incorporation of both prosthetic arrangement and individual anatomical details enables the virtual execution of critical procedures (e.g., implant placement, extended applications, etc.) through analysis of cross-sectional images and the reconstruction of 3-dimensional surface models. After verification, the utilization of digital technology including templates, navigation, combined techniques, and implant robots achieved seamless transfer of the virtual treatment plan to the actual surgical sites, ultimately leading to enhanced surgical outcomes with highly improved accuracy. In restoration delivery, digital techniques for impression, shade matching, and prosthesis fabrication have advanced, enabling seamless digital data conversion and efficient communication among clinicians and technicians. Compared with clinical medicine, artificial intelligence (AI) technology in dental implantology primarily focuses on diagnosis and prediction. AI-supported preoperative planning and surgery remain in developmental phases, impeded by the complexity of clinical cases and ethical considerations, thereby constraining widespread adoption., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Orchitis is a common reproductive disease of male animals, which has serious implications to human and animal reproduction. Additionally, phlorizin (PHN), a common polyphenol in apples and strawberries, has a variety of biological activities, including antioxidant, anti-inflammatory, anti-diabetic, and anti-aging activities. We aimed to determine the protective effects and potential mechanisms of PHN in lipopolysaccharide (LPS)-induced acute orchitis in mice., Method: After 21 days of PHN pretreatment, mice were injected with LPS to induce testicular inflammation, and then the changes of testicular tissue structure, expression of inflammatory factors, testosterone level, expression of testosterone-related genes, adhesion gene and protein expression were detected, and the structural changes in the intestinal flora after PHN treatment were further detected by 16SRNA., Result: Our results demonstrated that PHN treatment reduced LPS-induced testicular injury and body and testicular weight losses. The mRNA expression levels of pro-inflammatory cytokines-related genes and antioxidant enzyme activity were also decreased and elevated, respectively, by PHN administration; however, PHN treatment also reduced the LPS-induced decrease in testosterone levels in the testes. Additionally, further studies found that PHN increased the expression of marker proteins zonula occludens-1 (ZO-1) and occludin associated with the blood testosterone barrier compared with that in LPS treatment groups. To further examine the potential mechanisms of the protective effect of PHN on LPS-induced testicular injury, we compared the differences of gut microbiota compositions between the 100 mg/kg PHN treatment group and the control group using 16SRNA. Metagenomic analyses indicated that the abundances of Bacteroidetes , Muribaculaceae , Lactobacillaceae , uncultured bacterium f Muribaculaceae , and Lactobacillus in the PHN treatment group improved, while potential microbes that can induce intestinal diseases, including Verrucomicrobia , Epsilonbacteraeota , Akkermansiaceae , and Akkermansia decreased in the PHN treatment group., Conclusion: Our results indicate that PHN pretreatment might alleviate orchitis by altering the composition of gut microflora, which may provide a reference for reducing the occurrence of acute orchitis in male animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Li, Huang, Li, Zhang and Qu.)

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 μM (P<0.01) and 40 μM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 μM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In this study, we investigated the serum vitamin D level in overweight individuals and its correlation with the incidence of nonalcoholic fatty liver disease (NAFLD). Between May 2020 and May 2021, the Department of Gastroenterology at the People's Hospital of Henan University of Traditional Chinese Medicine treated a total of 321 outpatients and inpatients with NAFLD, who were included in the NAFLD group, while 245 healthy age- and gender-matched individuals were included in the control group. All the data were collected for the relevant indices, including fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine transaminase, and 25-hydroxy vitamin D (25[OH]D. The patients with NAFLD were divided into the normal BMI group, the overweight group, and the obese group, according to the body mass index, and the 25(OH)D levels were compared between the different groups. Spearman's correlation analysis was performed to analyze the correlation between the serum 25(OH)D level and NAFLD. Regarding the serum 25 (OH)D level, it was lower in the NAFLD group than in the control group ([18.36 + 1.41] µg/L vs [22.33 + 2.59] µg/L, t = ?5.15, P<0.001), and was lower in the overweight group than in the normal group ([18.09 ± 5.81] µg/L vs [20.60 ± 4.16] µg/L, t = 0.26, P = 0.041). The serum 25(OH)D level was thus negatively correlated with the incidence of NAFLD in overweight individuals (r = 0.625, P<0.05). In conclusion, the level of 25(OH)D decreased in patients with NAFLD with increasing BMI (normal, overweight, obese). Keywords: Nonalcoholic fatty liver disease, Vitamin D.

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P >0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P <0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P <0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q 1 , Q 3 ) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2 . The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2 , -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( P nonlinear <0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( P linear <0.001), hip circumference ( P linear <0.001), and calf circumference ( P linear <0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective: To investigate whether common genetic polymorphisms are associated with gonadotropin levels after down-regulation with daily gonadotropin-releasing hormone agonist and whether the polymorphisms of candidate variants influence the ovarian response to exogenous gonadotropins., Design: Genetic association study., Setting: University-affiliated in vitro fertilization center., Patients: Subjects enrolled in an exploratory exome-wide association study (n = 862), a replication exome-wide association study (n = 86), and a classifier validation study (n = 148) were recruited from September 2016 to October 2018, September 2019 to September 2020, and January 2021 to December 2021, respectively. The included patients were aged ≤40 years and had a basal follicle-stimulating hormone (FSH) ≤12 IU/L., Interventions: All participants received a luteal phase down-regulation long protocol. Genome DNA was extracted from the peripheral blood leukocytes. For the exploratory and replication cohorts, exome sequencing was conducted on a HiSeq 2500 sequencing platform. The multiplex polymerase chain reaction amplification technique and next-generation sequencing also were performed in the exploratory and replication cohorts. For the samples of the validation cohort, Sanger sequencing was performed., Main Outcome Measures: The primary endpoint was the gonadotropin levels after down-regulation, and the secondary endpoints were hormone levels and follicle diameters during stimulation, the total dose of FSH, duration of FSH stimulation, number of oocytes retrieved, and clinical pregnancy rate., Results: In the exploratory cohort, we identified that FSHB rs6169 (P=2.71 × 10 -24 ) and its single-nucleotide polymorphisms in high linkage disequilibrium were associated with the down-regulated FSH level. The same locus was confirmed in the replication cohort. Women carrying the C allele of FSHB rs6169 exhibited higher average estradiol level during stimulation (P=6.82 × 10 -5 ), shorter duration of stimulation, and less amount of exogenous FSH (P duration =0.0002; P dose =0.0024). In the independent validation set, adding rs6169 genotypes into the prediction model for FSH level after down-regulation enhanced the area under the curve from 0.560 to 0.712 in a logistic regression model, and increased prediction accuracy by 41.05% when a support vector machine classifier was applied., Conclusion: The C allele of FSHB rs6169 is a susceptibility site for the relatively high level of FSH after down-regulation, which may be associated with increased ovarian FSH sensitivity., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association of plasma vitamin B 12 level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B 12 and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B 12 , uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B 12 level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B 12 level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B 12 level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M ( Q 1 , Q 3 ) level of plasma vitamin B 12 was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B 12 level with plasma uric acid level after adjustment for covariates ( P <0.05). An IQR increase in plasma vitamin B 12 (237 pg/ml) was associated with a 6.36 (95% CI : 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B 12 with uric acid level ( P <0.001). Conclusion: There is a positive association of plasma vitamin B 12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.

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/m 2 group ( P interaction =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.

Objective: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine., Methods: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients., Results: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD., Conclusions: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914)., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median ( Q 1 , Q 3 ) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure ( P <0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95% CI : 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95% CI : 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95% CI : 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95% CI : 0.03, 0.29)×10 9 /L elevation in white blood cells, and 0.11 (95% CI : 0.02, 0.21)×10 9 /L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95% CI : 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95% CI : 1.11%, 7.10%) and 2.42% (95% CI : 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.

Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m 2 and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T 2 (19.1-22.1 kg/m 2 ) of BMI, the OR (95% CI ) of the female T 1 (<19.1 kg/m 2 ) and T 3 (≥22.2 kg/m 2 ) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T 2 (77-85 cm) of WC, the OR (95% CI ) of female T 1 (<77 cm) and T 3 (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.

Objective: To evaluate the association of lead exposure with stunting and underweight among children aged 3-5 years in China. Methods: Data was collected from China National Human Biomonitoring (CNHBM) between January 2017 and December 2018. A total of 3 554 children aged 3-5 years were included. Demographic characteristic, lifestyle and nutritional status were collected through questionnaires. Height and weight were measured by standardized method. Stunting and underweight status were determined by calculating height for age Z -score and weight for age Z -score. Blood and urine samples were collected to detect the concentrations of blood lead, urinary lead and urinary creatinine. Children were stratified into 4 groups ( Q 1 to Q 4 ) by quartiles of blood lead level and corrected urinary lead level, respectively. Complex sampling logistic regression models were applied to evaluate the association of the blood lead level, urinary lead level with stunting and underweight. Results: Among 3 554 children, the age was (4.09±1.06) years, of which 1 779 (80.64%) were female and 1 948 (55.84%) were urban residents. The prevalence of stunting and wasting was 7.34% and 2.96%, respectively. The M (Q 1 , Q 3 ) for blood lead levels and urinary lead levels in children was 17.49 (12.80, 24.71) μg/L, 1.20 (0.61, 2.14) μg/g Cr, respectively. After adjusting for confounding factors, compared with the lowest blood lead concentration group Q 1 , the risk of stunting gradually increased in the Q 3 and Q 4 group ( P trend =0.010), with OR (95% CI ) values of 1.40 (0.80-2.46) and 1.80 (1.07-3.04), respectively. Compared with the lowest urinary lead concentration group Q 1 , the risk of stunting still increased in the Q 3 and Q 4 group ( P trend =0.012), with OR (95% CI ) values of 1.69 (1.01-2.84) and 1.79 (1.05-3.06), respectively. The correlation between the lead exposure and underweight was not statistically significant ( P >0.05). Conclusion: Lead exposure is positively associated with the risk of stunting among children aged 3-5 years in China.

Objective: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors., Methods: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration., Results: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine., Conclusion: The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, exhibits recurrent mutations in various types of human cancers, including liver cancer. However, the function of ARID1A in the pathogenesis of liver cancer remains controversial. Here, we demonstrate that Arid1a knockout may result in states of different cell differentiation, as indicated by single-cell RNA sequencing (scRNA-seq) analysis. Bulk RNA-seq also revealed that Arid1a deficiency upregulated these genes related to cell stemness and differentiation, but downregulated genes related to the hepatic functions. Furthermore, we confirmed that deficiency of Arid1a increased the expression of hepatic stem/progenitor cell markers, such as Cd133 and Epcam, and enhanced the self-renewal ability of cells. Mechanistic studies revealed that Arid1a loss remodeled the chromatin accessibility of some genes related to liver functions. Thus, Arid1a deficiency might contribute to cancer development by increasing the number of stem/progenitor-like cells through dysregulating the expression of these genes related to cell stemness, differentiation and liver functions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To study the genetic polymorphism and population genetic parameters of 16 X-STR loci in Xinjiang Uygur population., Methods: The Golden e ye ® DNA identification system 17X was used to amplify 16 X-STR loci in 502 unrelated individuals (251 females and 251 males). The amplified products were detected by 3130 xl genetic analyzer. Allele frequencies and population genetic parameters were analyzed statistically. The genetic distances between Uygur and other 8 populations were calculated. Multidimensional scaling and phylogenetic tree were constructed based on genetic distance., Results: In the 16 X-STR loci, a total of 67 alleles were detected in 502 Xinjiang Uygur unrelated individuals. The allele frequencies ranged from 0.001 3 to 0.572 4. PIC ranged from 0.568 8 to 0.855 3. The cumulative discrimination power in females and males were 0.999 999 999 999 999 and 0.999 999 999 743 071, respectively. The cumulative mean paternity exclusion chance in trios and in duos were 0.999 999 997 791 859 and 0.999 998 989 000 730, respectively. The genetic distance between Uygur population and Kazakh population was closer, and the genetic distance between Uygur and Han population was farther., Conclusions: The 16 X-STR loci are highly polymorphic and suitable for identification in Uygur population, which can provide a powerful supplement for the study of individual identification, paternity identification and population genetics.

Background: Artificial intelligence (AI) has breathed new life into the lung nodules detection and diagnosis. However, whether the output information from AI will translate into benefits for clinical workflow or patient outcomes in a real-world setting remains unknown. This study was to demonstrate the feasibility of an AI-based diagnostic system deployed as a second reader in imaging interpretation for patients screened for pulmonary abnormalities in a clinical setting., Methods: The study included patients from a lung cancer screening program conducted in Sichuan Province, China using a mobile computed tomography (CT) scanner which traveled to medium-size cities between July 10 th , 2020 and September 10 th , 2020. Cases that were suspected to have malignant nodules by junior radiologists, senior radiologists or AI were labeled a high risk (HR) tag as HR-junior, HR-senior and HR-AI, respectively, and included into final analysis. The diagnosis efficacy of the AI was evaluated by calculating negative predictive value and positive predictive value when referring to the senior readers' final results as the gold standard. Besides, characteristics of the lesions were compared among cases with different HR labels., Results: In total, 251/3,872 patients (6.48%, male/female: 91/160, median age, 66 years) with HR lung nodules were included. The AI algorithm achieved a negative predictive value of 88.2% [95% confidence interval (CI): 62.2-98.0%] and a positive predictive value of 55.6% (95% CI: 49.0-62.0%). The diagnostic duration was significantly reduced when AI was used as a second reader (223±145.6 vs . 270±143.17 s, P<0.001). The information yielded by AI affected the radiologist's decision-making in 35/145 cases. Lesions of HR cases had a higher volume [309.9 (214.9-732.5) vs . 141.3 (79.3-380.8) mm 3 , P<0.001], lower average CT number [-511.0 (-576.5 to -100.5) vs . -191.5 (-487.3 to 22.5), P=0.010], and pure ground glass opacity rather than solid., Conclusions: The AI algorithm had high negative predictive value but low positive predictive value in diagnosing HR lung lesions in a clinical setting. Deploying AI as a second reader could help avoid missed diagnoses, reduce diagnostic duration, and strengthen diagnostic confidence for radiologists., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2157/coif). BS serves as an unpaid editorial board member of Annals of Translational Medicine from September 2020 to August 2022. The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

SPOCK1 is an extracellular proteoglycan and involved in tumor growth and metastasis in various cancers. 5-fluorouracil (5-FU) is commonly used for the treatment of colorectal cancer (CRC) in patients who receive concurrent chemoradiotherapy. However, the relationship between development of resistance to 5-FU and SPOCK1 remain unclear. In this study, we established two 5-fluorouracil (5-FU)-resistant CRC cell lines, HCT116/FU and LOVO/FU, and found that SPOCK1 is upregulated in 5-FU-resistance CRC cells compared with its parental cell line. knockdown of SPOCK1 in 5-FU-resistant CRC cells increases their sensitivity to 5-FU. In contrast, transient transfection of SPOCK1 enhanced HCT116 and LOVO cell resistance to 5-FU and reduced cell apoptosis. Mechanistically, SPOCK1 promoted 5-FU resistance by regulating PRRX1 expression and the downstream apoptosis signaling pathway. Taken together, our results revealed for the first time that SPOCK1 plays a crucial role in the resistance of CRC cells to 5-FU and indicated that targeting SPOCK1 may be a promising therapeutic strategy to overcome 5-FU resistance in CRC., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Disease situations are more aggressive in patients with childhood-onset systemic lupus erythematosus (cSLE) than in those with adult-onset SLE (aSLE). However, information on pregnant women with cSLE and its association with pregnancy outcomes is limited. This study aimed to compare pregnancies in patients with cSLE vs. aSLE, and further analyse the characteristics of cSLE in pregnant women and explore its association with adverse pregnancy outcomes., Methods: Altogether, data of 167 pregnancies from 150 women, including 22 pregnancies with cSLE and 145 pregnancies with aSLE, were retrospectively analysed. Characteristics and disease activity were compared between the cSLE and aSLE groups during pregnancy. Associations between cSLE and the risk of active SLE (SLEPDAI > 4), active lupus nephritis (LN), and adverse pregnancy outcomes were analysed using logistic regression., Results: The cSLE group had a higher incidence of active SLE (12/22 vs. 30/145, P = 0.001) and active LN (11/22 vs. 26/145, P = 0.001) than the aSLE group. In the multivariable analysis, cSLE was a risk factor for active SLE and active LN during pregnancy, with ORs of 4.742 (95%CI 1.678-13.405, P = 0.003) and 4.652 (95%CI 1.630-13.279, P = 0.004), respectively. No significant association between cSLE and the risk of composite adverse gestational outcomes was identified after sequentially adjusting pre-pregnancy characteristics and pregnancy factors (P > 0.05)., Conclusion: Disease activity of women with cSLE in pregnancy was more aggressive than that of women with aSLE, which was similar to the characteristics of non-pregnant women with SLE. cSLE might have indirect effects on the risk of adverse pregnancy outcomes through LN and active disease. Therefore, closely monitoring patients with cSLE during pregnancy is crucial., (© 2022. The Author(s).)

Herein, the Rh-catalyzed consecutive C-H bond olefination/annulation/olefination cascade, tandemly directed by sulfonamide and ester groups, has been developed under mild conditions with the assistance of 1-adamantane carboxylic acid. A seven-membered metallacycle including an ester group was preferred to the five-membered one including a sulfonamide group for the third C-H activation. In this transformation, the Rh catalyst exhibits its high reactivity by catalyzing a triple C-H activation process with a low catalyst loading at 50 °C. This method can be applied in the construction of various pharmaceutical derivatives.

Objectives: To construct a Felis catus STR loci multiplex amplification system and to evaluate its application value by testing the technical performance., Methods: The published Felis catus STR loci data were reviewed and analyzed to select the STR loci and sex identification loci that could be used for Felis catus individual identification and genetic identification. The fluorescent labeling primers were designed to construct the multiplex amplification system. The system was validated for sensitivity, accuracy, balance, stability, species specificity, tissue identity and mixture analysis, and investigated the genetic polymorphisms in 145 unrelated Felis catus samples., Results: Sixteen Felis catus autosomal STR loci and one sex determining region of Y (SRY) were successfully selected, and constructed a multiplex amplification system containing the above loci. The complete profile of all alleles could still be obtained when the amount of DNA template was as low as 0.25 ng. There was no specific amplification peak in other common animal samples. Population genetic surveys showed that total discrimination power (TDP) of the 16 STR loci was 1-3.57×10 -20 , the cumulative probability of exclusion (CPE) was 1-6.35×10 -5 and the cumulative probability of matching was 3.61×10 -20 ., Conclusions: The Felis catus STR multiplex amplification system constructed in this study is highly sensitive, species-specific, and accurate in typing results, which can provide an effective solution for Felis catus species identification, individual identification and kinship identification in the field of forensic science.

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95% CI ) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95% CI ) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Background: The association between high-sensitivity C-reactive protein (hsCRP) levels and all-cause mortality for the oldest-old (aged 80 years or older) remains unclear. We aimed to investigate the associations between hsCRP concentrations and the risks of all-cause mortality, and further identify the potential modifying factors affecting these associations among the oldest-old., Methods: This prospective, community-based cohort study included 2,206 participants aged 80 years or older (median age 93.0 years) from the Healthy Aging and Biomarkers Cohort Study. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for all-cause mortality according to hsCRP quartiles and recommendation for relative risk categories of hsCRP levels (< 1.0, 1.0-3.0, and > 3.0 mg/L), with adjustment for sociodemographic information, lifestyle, physical examination, medical history, and other potential confounders., Results: During a median follow-up period of 3.1 years (IQR: 1.6-3.9 years), 1,106 deaths were verified. After full adjustment for potential confounders, a higher hsCRP concentration was positively associated with an increased risk of all-cause mortality ( P for trend < 0.001). Compared with the lowest quartile, the fully adjusted HRs of the second, third, and fourth quartiles were 1.17 (95% CI: 0.94, 1.46), 1.28 (95% CI: 1.01, 1.61), and 1.49 (95% CI: 1.20, 1.87), respectively. The association of hsCRP with all-cause mortality was modified by smoking status ( P for interaction = 0.011), an increased risk of hsCRP with all-cause mortality showed among non-current smokers (HR: 1.17; 95% CI: 1.07, 1.28), but no significance was observed in current smokers (HR: 0.83; 95% CI: 0.66, 1.18)., Conclusions: Our study indicated that elevated hsCRP concentrations were associated with a higher risk of all-cause mortality among Chinese oldest-old. Future studies investigating additional factors of disease and aging processes are needed to obtain a better understanding of the mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Li, Yang, Cao, Cheng, Zhao, Zhang, Lv, Li, Zhou, Li, Qu, Yin, Liu, Wu, Shi and Mao.)

Objective: To construct an easy-to-use risk prediction tool for 6-year risk of activities of daily living(ADL) disability among Chinese elderly aged 65 and above. Methods: A total of 34 349 elderly aged 65 and above were recruited from the Chinese Longitudinal Healthy Longevity Survey. Demographic characteristics, lifestyle and chronic diseases of the elderly were collected through face-to-face interviews. The functional status of the elderly was evaluated by the instrumental activities of daily living(IADL) scale. The mental health status of the elderly was evaluated by the Mini-Mental State Examination. The height, weight, blood pressure and other information of the subjects were obtained through physical examination and body mass index(BMI) was calculated. The ADL status was evaluated by Katz Scale at baseline and follow-up surveys. Taking ADL status as the dependent variable and the key predictors were selected from Lasso regression as the independent variables, a Cox proportional risk regression model was constructed and visualized by the nomogram tool. Area under the receiver operating characteristic curve(AUC) and calibration curve were used to evaluate the discrimination and calibration of the model. A total of 200 bootstrap resamples were used for internal validation of the model. Sensitivity analysis was used to evaluate the robustness of the model. Results: The M(Q 1 , Q 3 ) of subjects' age as 86(75, 94) years old, of which 9 774(46.0%) were males. A total of 112 606 person-years were followed up, 4 578 cases of ADL disability occurred and the incidence density was 40.7/1 000 person-years. Cox proportional risk regression model analysis showed that older age, higher BMI, female, hypertension and history of cerebrovascular disease were associated with higher risk of ADL disability [ HR (95% CI ) were 1.06(1.05-1.06), 1.05(1.04-1.06), 1.17(1.10-1.25),1.07(1.01-1.13) and 1.41(1.23-1.62), respectively.]; Ethnic minorities, walking 1 km continuously, taking public transportation alone and doing housework almost every day were associated with lower risk of ADL disability [ HR( 95% CI ): 0.71(0.62-0.80), 0.72(0.65-0.80), 0.74(0.68-0.82) and 0.69(0.64-0.74), respectively]. The AUC value of the model was 0.853, and the calibration curve showed that the predicted probability was highly consistent with the observed probability. After excluding non-intervening factors(age, sex and ethnicity), the AUC value of the model for predicting the risk of ADL disability was 0.779. The AUC values of 65-74 years old and 75 years old and above were 0.634 and 0.765, respectively. The AUC values of the model based on walking 1 km continuous and taking public transport alone in IADL and the model based on comprehensive score of IADL were 0.853 and 0.851, respectively. Conclusion: The risk prediction model of ADL disability established in this study has good performance and robustness.

Objectives: To evaluate the ability of the ForenSeq TM DNA Signature Prep kit (ForenSeq kit) in analyzing the sequence information of STRs in Zhejiang She ethnic group and its forensic application efficacy., Methods: A total of 50 Zhejiang She ethnic group samples were sequenced with the ForenSeq kit on the MiSeq FGx platform. The data was analyzed using ForenSeq TM universal analysis software to obtain the motif structure and flank regions of the 58 STRs, then compared with PCR-CE typing results to test the consistency. At last, the allele frequency and population genetic parameters were calculated., Results: A total of 448 sequence polymorphic alleles were detected in 50 samples of Zhejiang She ethnic group. Compared with fragment length polymorphism detected by PCR-CE, 82 alleles were increased by MPS detection based on ForenSeq kit, and 7 SNPs variation were detected in the flanking regions of 6 loci. The 22 male individuals were genotyped, and total 19 haplotypes were detected in 24 Y chromosome STRs of these 22 males. The cumulative discrimination power of the 27 autosomal STRs was 1-8.87×10 -30 , the cumulative probability of exclusion of duo-testing was 0.999 999 962 640 657, the cumulative probability of exclusion of trios-testing was 0.999 999 999 999 633., Conclusions: Based on MPS typing technology, using the ForenSeq kit greatly improves the detection efficiency. In addition, the 58 STRs have good genetic polymorphisms in Zhejiang She ethnic group, which are suitable for individual identification and paternity identification in forensic application.

Objective: To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults., Methods: Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment., Results: The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio ( OR ) for cognitive impairment in individuals with sarcopenia was 2.55 [95% confidence interval (95% CI ): 1.86-3.50]. Compared with individuals in the first quartile (Q 1 ) of calf circumference, the adjusted OR s in the second, third, and fourth quartiles (Q 2 , Q 3 , and Q 4 ) were 0.75 (95% CI : 0.58-0.96), 0.59 (95% CI : 0.44-0.79), and 0.62 (95% CI : 0.45-0.8), respectively. Compared with individuals in Q 1 of handgrip strength, the adjusted OR s for Q 2 , Q 3 , and Q 4 were 0.49 (95% CI : 0.38-0.62), 0.31 (95% CI : 0.23-0.41), and 0.30 (95% CI : 0.21-0.44), respectively., Conclusion: Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

ARID1A, encoding a subunit of SWI/SNF chromatin remodeling complex, is widely recognized as a tumor suppressor gene in multiple tumor types including liver cancer. Previous studies have demonstrated that ARID1A deficiency can cause liver cancer metastasis, possibly due to the altered chromatin organization, however the underlying mechanisms remain poorly understood. To address the effect of Arid1a deficiency on chromatin organization, we generated chromatin interaction matrices, and exploited the conformation changes upon Arid1a depletion in hepatocytes. Our results demonstrated that Arid1a deficiency induced A/B compartment switching, topologically associated domain (TAD) remodeling, and decrease of chromatin loops. Further mechanism studies revealed that ATPase BRG1 of SWI/SNF complex could physically interact with RAD21, a structural subunit of chromatin architectural element cohesin; whereas ARID1A deficiency significantly diminished the coupled BRG1-RAD21. Interestingly, the tumor-associated genes within the switched compartments were differentially expressed depending upon Arid1a depletion or not. As a consequence of ARID1A deficiency-induced conformational alteration, the dysregulation of some genes such as PMP22 and GSC, promoted the invasion capacity of liver cancer cells. This study provides an insight into liver cancer tumorigenesis and progression related to ARID1A mutations., (© 2021. The Author(s).)

Background and Aims: Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods . Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed., Results: A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s, p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups., Conclusion: ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075., Competing Interests: All authors declare no potential conflicting interests related to this paper., (Copyright © 2021 Ying-Hao Song et al.)

Objective: To analyze the association of the cadmium internal exposure with chronic kidney disease (CKD) in Chinese adults aged 18 and older. Methods: A total of 9 821 adults aged 18-79 from the China National Human Biomonitoring (CNHBM) from 2017 to 2018 were included. Blood and urine cadmium exposure levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), and urine cadmium levels were adjusted with urine creatinine; CKD were defined by estimated glomerular filtration (eGFR) using the chronic kidney disease epidemiology collaboration (CKD-EPI). Weights were considered due to complex sampling process for in statistical analysis. Logistic regression is used to analyze the association of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine exposure levels with CKD, and restricted cube spline (RCS) was used to assess the exposure-response curve of blood cadmium, urine cadmium and urine cadmium adjusted with creatinine with CKD. Results: The weighted age was 44.75 and males accounted for 61.1%. The prevalence rate of CKD was 12.7%. The geometric mean values of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine were 0.96 μg/L, 0.61 μg/L, and 0.58 μg/g. After adjusting for confounding factors, the weighted logistic regression showed that the lowest quintile ( Q 1 ) was compared with the odds ratio ( OR ) of the highest quintile ( Q 5 ) of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine and the 95% confidence interval ( CI ) was 1.80 (1.02-3.20), 1.77 (0.94-3.31) and 1.94 (1.11-3.37) respectively. In the restricted cubic spline regression model, non-linear association of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine with CKD were observed after adjusting for related confounding factors ( P <0.001, 0.018, 0.031 respectively). The risk of CKD increased with the increment of cadmium exposure without risk threshold, and the exposure response curve was steeper at low cadmium exposure. Conclusions: Among Chinese adults aged 18 and older, cadmium exposure is positively associated with the risk of chronic kidney disease.

Abstract: Objective To study the genetic polymorphism of whole mitochondrial DNA （mtDNA） genomes in She population in Zhejiang and to explore the maternal genetic structure of the She population. Methods Whole mtDNA genomes of 231 unrelated individuals from She population in Zhejiang Province were sequenced. The number of mutations and population genetics parameters such as, the haplotype diversity （HD）, discrimination power （DP）, and random match probabilities （RMP） were analyzed. The mtDNA haplogroups of Zhejiang She population were classified, and the maternal genetic relationships between She and nine other Chinese populations were estimated. Results In 231 Zhejiang She samples, 8 507 mutations （702 types） were observed and the samples were classified into 94 haplogroups. The HD, DP and RMP values were 0.998 6, 0.994 2 and 0.005 8, respectively. The lowest genetic differentiation degree （ F st =0.006 89） was detected between Zhejiang She population and southern Han population. Principal component analysis （PCA） and median-joining network analysis showed that the genetic distance of Zhejiang She population with Guangxi Yao, Yunnan Dai and Southern Han populations was relatively close, but the population still had some unique genetic characteristics. Conclusion The whole mtDNA genomes are highly polymorphic in Zhejiang She population. The Zhejiang She population contains complex and diverse genetic components and has a relatively close maternal genetic relationship with Guangxi Yao, Yunnan Dai and Southern Han populations. Meanwhile, Zhejiang She population has kept its unique maternal genetic components., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Objective: To investigate the effect of plasma uric acid level on the incident risk of type 2 diabetes mellitus (T2DM) among the oldest old (those aged ≥80 years). Methods: Participants were recruited from the Healthy Aging and Biomarkers Cohort Study (HABCS), which conducted a baseline survey in 2008-2009 and follow-up of 3 times in 2011-2012, 2014, and 2017-2018, respectively. A total of 2 213 oldest old were enrolled in this study. The general demographic, socioeconomic, lifestyle and disease data of the oldest old were collected, and physical measurements were made for the oldest old. Fasting venous blood was collected for uric acid and blood glucose detection. Information on the incident and death of T2DM were collected through the follow-up. Cox proportional hazard regression model was used to explore the association of hyperuricemia and plasma uric acid level with the incidence of T2DM. Restricted cubic spline (RCS) function was used to explore the dose-response relationship of plasma uric acid levels with the risk of T2DM. Results: The age of participants was (93.2±7.6) years old, and 66.7% of the participants (1 475) were female. The plasma uric acid level at baseline was (289.1±88.0)μmol/L, and the prevalence of hyperuricemia was 13.3% (294 cases). During 9 years of cumulative follow-up of 7 471 person-years (average of 3.38 years for each), 122 new cases of T2DM occurred and the incidence density was 1 632.98/10 5 person year. Cox proportional hazards regression analysis showed that per 10μmol/L increase in plasma uric acid level, the risk of T2DM increased by 1.1% [ HR (95% CI ): 1.011 (1.004, 1.017)]. Compared with the participants with the lowest quintile of plasma uric acid ( Q 1 ), the risk of diabetes increased by 20.7 % among the oldest old with uric acid in the highest quintile ( Q 5 ) [ HR (95% CI ):1.207 (1.029, 1.416)]. The risk of T2DM was 19.2% higher in the hyperuricemia group than that in the oldest old with normal plasma uric acid [ HR (95% CI ): 1.192 (1.033, 1.377)]. RCS function showed that the risk of T2DM increased with the increase in plasma uric acid levels in a nonlinear dose-response relationship ( P =0.016). Conclusion: The incident risk of T2DM increases with the elevates of plasma uric acid levels in the oldest old.

Abstract: Objective To assess the feasibility of the rbcL sequence of chloroplast DNA as a genetic marker to identify Cannabis sativa L. Methods The rbcL sequences in 62 Cannabis sativa L. samples, 10 Humulus lupulus samples and 10 Humulus scandens DNA samples were detected, and 96 rbcL sequences of the Cannabaceae family were downloaded from Genbank. Sequence alignment was performed by MEGA X software, the intraspecific and interspecific Kimura-2-Parameter （K2P） genetic distances were calculated, and the system clustering tree was constructed. Results The rbcL sequence length acquired by sequencing of Cannabis sativa L. and Humulus scandens were 617 bp and 649 bp, respectively, and two haplotypes of Cannabis sativa L. were observed in the samples. The BLAST similarity search results showed that the highest similarity between the sequences acquired by sequencing and Cannabis sativa L. rbcL sequences available from Genbank was 100%. The genetic distance analysis showed that the maximum intraspecific genetic distance （0.004 9） of Cannabis sativa L. was less than the minimum interspecific genetic distance （0.012 9）. The results of median-joining network and system clustering tree analysis showed that Cannabis sativa L. and other members of the Cannabaceae family were located in different branches. Conclusion The rbcL sequence could be used as a DNA barcode for identifying Cannabis sativa L., and combined with comparative analysis of the rbcL sequence and system cluster analysis could be a reliable and effective detection method for Cannabis sativa L. identification in forensic investigation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

β-carotene is a precursor of vitamin A and has multiple physiological functions. Producing β-carotene by microbial fermentation has attracted much attention to consumers' preference for natural products. This study focused on improving β-carotene production by constructing codon-adapted genes and minimizing intermediate accumulation. The codon-adapted CarRA and CarB genes from the industrial strain of Blakeslea trispora were integrated into the genome of the Yarrowia lipolytica to construct YL-C0, the baseline strain for producing β-carotene. Thereafter, the β-carotene biosynthetic pathway's metabolic balance was accurately regulated to reduce the intermediates' accumulation. Notably, the β-carotene content increased by 21 times to reach 12.5 dry cell weight (DCW) mg/g when minimizing HMG-CoA and FPP accumulation. Further, we improved the expression levels of the CarRA and CarB genes to minimize the accumulation of phytoene and lycopene. Total production of β-carotene of 1.7 g/L and 21.6 mg/g DCW was achieved. These results reveal that the rate-limiting enzymes CarRA and CarB of B. trispora exhibited higher catalytic activity than the same enzymes from other microorganisms. Promoting metabolic balance by minimizing the accumulation of intermediates is a very effective strategy for increasing β-carotene. The β-carotene-producing strain constructed in this study has established the foundation for its potential use in industrial production. These successful engineering strategies also provide a foundation for large-scale production of other terpenoids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Qu, Dong, Wang, Hu and Meng.)

The convenient preparation of N2-unprotected five-membered cyclic guanidines was achieved through a cascade [3 + 2] cycloaddition between organo-cyanamides and α-haloamides under mild conditions in good to excellent yields (up to 99%). The corresponding cyclic guanidines could be easily transformed into hydantoins via hydrolysis.

The conserved zona pellucida (ZP) domain is found in hundreds of extracellular proteins that are expressed in various organs and play a variety of roles as structural components, receptors and tumor suppressors. A liver-specific zona pellucida domain-containing protein (LZP), also named OIT3, has been shown to be mainly expressed in human and mouse hepatocytes; however, the physiological function of LZP in the liver remains unclear. Here, we show that Lzp deletion inhibited very low-density lipoprotein (VLDL) secretion, leading to hepatic TG accumulation and lower serum TG levels in mice. The apolipoprotein B (apoB) levels were significantly decreased in the liver, serum, and VLDL particles of LZP-deficient mice. In the presence of LZP, which is localized to the endoplasmic reticulum (ER) and Golgi apparatus, the ER-associated degradation (ERAD) of apoB was attenuated; in contrast, in the absence of LZP, apoB was ubiquitinated by AMFR, a known E3 ubiquitin ligase specific for apoB, and was subsequently degraded, leading to lower hepatic apoB levels and inhibited VLDL secretion. Interestingly, hepatic LZP levels were elevated in mice challenged with a high-fat diet and humans with simple hepatic steatosis, suggesting that LZP contributes to the physiological regulation of hepatic TG homeostasis. In general, our data establish an essential role for LZP in hepatic TG transportation and VLDL secretion by preventing the AMFR-mediated ubiquitination and degradation of apoB and therefore provide insight into the molecular function of LZP in hepatic lipid metabolism., Competing Interests: The authors have declared that no competing interests exist.

Objective: The purpose of this study was to establish a nomogram for predicting the severity of acute pancreatitis (AP) and verify its predictive value., Patients and Methods: A total of 571 AP patients received by Ordos Central Hospital from January 2015 to December 2018 were included in this study. According to the 2012 Revised Atlanta classification, the included subjects were classified into severe AP (SAP) group and non-severe AP (NSAP) group [including patient with mild AP (MAP) and moderately SAP (MSAP)]. The baseline characteristics, imageological data and pathological data within 24 h after the disease onset between the two groups were analyzed using One-way analysis of variance (one-way ANOVA). R language was used for establishing a predictive nomogram, whose performance was verified by clinical data of 150 AP cases collected from December 2018 to December 2019., Results: One-way ANOVA shows that SAP and NSAP patients show significant differences in sex, calcium ions, creatinine, neutrophils ratio, lymphocytes ratio and eosinophils ratio (p<0.05). A predictive nomogram was accordingly established using the six indicators. Validation on this predictive nomogram showed high internal validation concordance index (C-index) of 0.69 (95% CI, 0.64-0.74), and high external validation C-index of 0.71 (95% CI, 0.67-0.76)., Conclusions: This nomogram can be used as a clinical tool to predict the severity of SAP.

Objective: To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over. Method: Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups ( Q 1 - Q 4 ) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results: Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95% CI of cognition impairment was 1.05 (1.01-1.10) for every 10 μg/L increase in blood lead concentration in elderly; Compared with the elderly in Q 1 , the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95% CI of Q 2 , Q 3 and Q 4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion: Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.

Objective: To investigate the association between oxygen saturation (SpO 2 ) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods: The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2 <94% was defined as abnormal). Results: The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2 . During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P< 0.001). After adjusting for confounding factors, compared to participants with normal SpO 2 , participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI ) of 1.62 (1.31-2.02); HR (95 % CI ) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2 group, respectively; HR (95% CI ) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion: Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective: The study is to examine association of sleep duration and cognitive impairment in the older adults aged 65 years and older in China. Methods: We analyzed data from 2017-2018 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 14 966 participants were included in the analysis. Data with respect to socioeconomic status, community involvement, behavior pattern, diet, life style, family structure, disease condition, mental health and cognitive function were collected. Cognitive function was measured with Mini-mental State Examination (MMSE). We conducted generalized linear mixed models to examine associations of sleep duration with cognitive impairment, and subgroup analyses of sex and age were conducted. Results: Among 14 966 participants, the percentage of participants aged 65 to 79 years, 80 to 89 years, 90 to 99 years and 100 years and older was 5 148 (4.40%), 3 777 (25.24%), 3 322 (22.20%) and 2 719 (18.16%), respectively. A total of 2 704 participants reported sleep duration of 5 h and less, and 3 883 reported 9 h and more, accounting for 18.94% and 27.19%, respectively. In total, 3 748 were defined with cognitive impairment, accounting for 25.04%. The results of generalized linear mixed models showed that both short (≤5 h) and long (≥ 9 h) sleep duration were associated with cognitive impairment compared with sleep duration of 7 h, with OR (95% CI ) of 1.35(1.09-1.68) and 1.70(1.39-2.07), respectively. The association of sleep duration with cognitive impairment was more obvious in males and individuals aged 65 to 79 years old. Conclusion: Short or long sleep duration was responsible for increased risk of cognitive impairment in older Chinese.

Objective: To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China. Methods: A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia. Results: A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95% CI : 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95% CI : 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion: Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

Recently, the combination of radical fluoroalkylation of alkenyl or alkynyl moieties and 1,4-functional group migration (1,4-FGM) has emerged as a powerful strategy for the synthesis of fluorine-containing compounds. In this article, some representative reactions of 1,4-FGM-mediated radical fluoroalkylation of N-(arylsulfonyl)acrylamides, tertiary alcohol-containing alkynes, tertiary alcohol-containing alkenes and intermolecular 1,4-FGM-type substrates have been discussed based on the types of substrates.

Purpose: Lung ultrasonography (LU) is useful to assess lung lesions and variations at bedside. To investigate the results of LU in severe and critical patients with coronavirus disease 2019 (COVID-19), we performed a single-institution study to evaluate the related lung lesions and variations, and prophylactic strategies, in a large referral and treatment center., Methods: We included 91 adult patients with severe and critical COVID-19, namely 62 males and 29 females, with an average age of 59 ± 11 years, who underwent LU. We collected the following patient information: sex, age, days in hospital, and days in ICU. In the ultrasound examinations, we recorded the presence of discrete B lines, confluent B lines, consolidation, pleural thickening, pleural effusion, and pneumothorax (PTX)., Results: Among the 91 severe and critical patients, 59 cases had scattered B lines, 56 cases had confluent B lines, 58 cases had alveolar-interstitial syndrome (AIS), 48 cases had lung consolidation, six cases had pleural thickening, 39 cases had pleural effusion (average depth of the pleural effusion: 1.0 ± 1.5 cm), and 20 patients developed PTX. In the Cox multivariate analysis, there were significant differences in age, hospitalization days, ICU days, and lung consolidation., Conclusion: Lung ultrasonography performed at the bedside can detect lung diseases, such as B lines, PTX, pulmonary edema, lung consolidation, pleural effusion, and variations of these findings. Our findings support the use of LU and measurements for estimating factors, and monitoring response to therapy in severe and critical COVID-19 patients., (© 2020 The Authors. Echocardiography published by Wiley Periodicals LLC.)