Global Burden of Dementia Death from 1990 to 2019, with Projections to 2050: An Analysis of 2019 Global Burden of Disease Study.

BACKGROUND: Dementia is a growing global health challenge. Quantifying the current burden and predicting the future increases of dementia-related deaths are necessary to enhance effective policy decisions and health system planning. METHODS: Data on dementia mortality was derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study. The 2020-2050 dementia-related deaths were forecasted using the Bayesian age-period-cohort model. RESULTS: Globally, the number of dementia-related death increased from 0.56 million in 1990 to 1.62 million in 2019 and were estimated to increase to 4.91 million by the year 2050. Metabolic risk factors would become the most important modifiable risk factors affecting dementia death which account for 28.10% of dementia related death by the year 2050. For different Socio-demographic Index (SDI) regions, the low SDI region would have the highest age-standardized mortality rate (ASMR) (29.16 per 100,000) by 2050. Moreover, the number of dementia-related deaths under the age of 70 years was predicted to reach 0.18 million by 2050. CONCLUSIONS: Dementia related death remains a global health problem, and health policies targeting metabolic risk factors may be an important way to alleviate this problem.

[Fetoscopy for intrauterine diagnosis and treatment of amniotic band syndrome: a clinical analysis of 7 cases and literature review].

Objective: To summarize the clinical value of fetoscopy in the prenatal diagnosis and treatment of amniotic band syndrome (ABS). Methods: A retrospective analysis was conducted on the clinical data of seven ABS fetuses who underwent prenatal fetoscopic intervention at the Third Affiliated Hospital of Zhengzhou University from December 2020 to August 2023. Literatures related to fetoscopic treatment of ABS were searched in databases including China National Knowledge Infrastructure, Wanfang Data, and PubMed. Clinical data were extracted and the characteristics and intervention effects of fetoscopic surgery in the treatment of ABS were summarized. Results: (1) Preoperative evaluation: the gestational age at diagnosis for the seven ABS fetuses was (19.8±4.4) weeks, and the gestational age at fetoscopic intervention was (22.2±2.8) weeks. The indications for fetoscopic intervention included umbilical cord involvement (3 cases), limb amniotic band with circular constriction (2 cases), and unclear visualization of digits (3 cases). (2) Pregnancy outcomes: among the seven ABS fetuses, four cases underwent selective termination of pregnancy due to severe intrauterine limb amputation, and three cases underwent fetoscopic lysis of amniotic bands. Among the latter three cases, one case experienced intrauterine fetal death (IUFD) two weeks after the procedure, and two cases had good postoperative outcomes. (3) Literature review: a total of 40 cases, including 37 cases from 17 articles and three cases from our institution, were included in the analysis. The indications for fetoscopic surgery included limb amniotic band with circular constriction and involvement of the umbilical cord. The success rate of the surgery was 82% (33/40), and 78% (29/37) of the affected limbs retained good functionality. Premature rupture of membranes was the most common complication, with an incidence rate of 48% (16/33). The average interval from the surgery to membrane rupture was (6.1±5.1) weeks, and the average interval from the surgery to delivery was (10.5±4.1) weeks, with an average gestational age at delivery of (33.7±3.6) weeks. The pregnant women were divided into single Trocar group (27 cases) and double Trocar group (13 cases) based on the surgical approach. The success rates in single Trocar group and double Trocar group were 78% (21/27) and 12/13, respectively, and the difference was not statistically significant (χ2=0.474, P=0.491). The gestational age of delivery in the single Trocar group and double Trocar group was (32.7±3.4) and (35.4±3.2) weeks, respectively, and the difference was statistically significant (t=-2.185, P<0.05). There were no statistically significant differences in the success rate of the surgery, incidence of premature rupture of membranes, interval between surgery and membrane rupture, interval between surgery and delivery, and preterm delivery rate between the two groups (all P>0.05). Conclusions: Fetoscopy could be used for prenatal assessment and intrauterine treatment of ABS. Fetoscopic lysis of amniotic bands may be an effective method for treating ABS, which helps preserve limb function and prevent intrauterine limb amputation and IUFD.

Long-term outcomes of fistula-tract laser closure for complex perianal fistulizing Crohn's disease.

BACKGROUND: Fistula-tract laser closure (FiLaC™) has shown promising outcomes in perianal fistulizing Crohn's disease (pfCD). However, most studies assessed a mixed cohort encompassing pfCD and cryptoglandular fistulas during a short follow-up period. This study aimed to evaluate the long-term treatment outcomes of FiLaC™ in patients with complex pfCD. METHODS: Data from patients with complex pfCD who underwent FiLaC™ during deep remission of Crohn's disease between January 2019 and December 2020 were retrospectively analyzed. Patient demographics, surgery history, and medication strategy were registered before surgery. Follow-ups were scheduled at 1, 2, and 3 months after FiLaC™, and at 2-month intervals thereafter. The primary endpoint was clinic healing, while clinic remission/unhealed/recurrence were classified as unhealed. Additionally, adverse events and Wexner fecal incontinence score were documented. RESULTS: Forty-nine patients (40 men and 9 women) with a median age of 26.0 (19.0-35.5) years were included with a median follow-up of 50.0 (39.5-54.0) months. Of these, 31 (63.3%) patients achieved fistula healing, 3 (6.1%) experienced improvement, 3 (6.1%) remained unhealed, and 12 (24.5%) experienced recurrence. Montreal A category was lower in the healed group (P < 0.001). No major complications, such as bleeding or fecal or urinary incontinence, were observed, and pain was transient. The Wexner incontinence score decreased significantly at the last available follow-up, indicating an intact postoperative continence function (P = 0.014). PCDAI scores were significantly higher in the unhealed group (P = 0.041). CONCLUSION: FiLaC™ is an efficient and safe sphincter-saving procedure for patients with complex pfCD.

Transcriptome analysis of long non-coding RNA associated with embryonic muscle development in chickens.

1. Skeletal muscle is an important component of chicken carcass. In chickens, the number of muscle fibres is fixed during the embryonic period, and muscle development during the embryonic period determines the muscle development potential after hatching.2. Beijing-You (BY) and Cornish (CN) chickens show completely different growth rates and body types, and two breeds were used in this study to explore the role of lncRNAs in muscle development during different chicken embryonic periods. A systematic analysis of lncRNAs and mRNAs were conducted in the pectoral muscle tissues of BY and CN chickens at embryonic days 11 (ED11), 13 (ED13), 15 (ED15), 17 (ED17), and 1-day-old (D1) using RNA-seq. A total of 4,104 differentially expressed transcripts (DETs) were identified among the five stages, including 2,359 lncRNAs and 1,745 mRNAs.3. The number of DETs between the two breeds at ED17 (1,658 lncRNAs and 1,016 mRNAs) was much higher than the total number of DET at all the other stages (692 lncRNAs and 729 mRNAs), indicating that the two breeds show the largest difference in gene regulation at ED17.4. Correlation analysis was performed for all differentially expressed lncRNAs and mRNAs during the five periods. Forty-three, cis interaction pairs of lncRNA-mRNA related to chicken muscle development were predicted. The expression of four pairs was verified, and the results showed MSTRG.12395.2-FGFBP2 and MSTRG.18590.6-FMOD were significantly up-regulated in CN at ED11 compared to BY and might be important candidate genes for embryonic muscle development.

[Feasibility and safety study of distal radial artery approach in emergency PCI of elderly STEMI patients].

Objective: To investigate the feasibility and safety of distal radial artery approach in emergency percutaneous coronary intervention(PCI) of elderly ST-segment elevation myocardial infarction(STEMI) patients. Methods: This study is a cross-sectional study. Elderly patients with acute myocardial infarction who received emergency PCI at the Third Central Hospital of Tianjin from January 2020 to December 2022 were selected. They were divided into the distal radial artery group and the classic radial artery group based on the puncture location. The success rate, puncture time, surgical success rate, and surgical time of the two groups were observed; The incidence of complications in patients, including radial artery occlusion rate, radial artery spasm rate, local hematoma rate, aneurysm incidence rate were recorded. Results: There were 70 cases in the distal radial artery group, including 33 males (47.1%), aged (65.6±6.7) years old; There were 70 cases in the classic radial artery group, including 35 males (50.0%), aged (66.4±6.9) years old. There was no statistically significant difference in puncture success rate, puncture time, surgical success rate, and surgical time between the distal radial artery group and the classical radial artery group (P>0.05). The incidence of radial artery occlusion in the distal radial artery group was significantly lower than that in the classical radial artery group (1.4% vs. 8.6%, P=0.024). The postoperative compression time in the distal radial artery group was significantly shorter than that in the classical radial artery group ((291.6±10.5) min vs. (343.5±9.8) min, P=0.047). There was no statistically significant difference in the incidence of radial artery spasm, local hematoma, and aneurysm between the two groups (P>0.05). Conclusions: The distal radial artery approach has a lower radial artery occlusion rate, shorter compression time, and better safety. It can be used as a new approach for emergency PCI in elderly patients with STEMI for clinical application.

[Comparison of efficacy and safety between domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer].

Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

[The association between body mass index and in-hospital major adverse cardiovascular and cerebral events in patients with acute coronary syndrome].

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

[Advances in research on the role of immune cells in optic nerve injury].

Optic nerve injury can result in the loss of retinal ganglion cells (RGCs) and their axons, representing a significant cause of irreversible vision impairment. Immune response is a common step following injury, and it often exhibits contrasting effects in optic nerve pathologies. Immune cells play a crucial role in this process, and understanding the differentiation of various immune cells post-injury, mitigating their neurotoxicity, and directing them towards a beneficial outcome for the protection of RGCs and axons are vital for optic nerve preservation. This paper provides a comprehensive review of the research progress on immune cells such as macrophages, microglia, T cells, and others in the field of optic nerve injury. Additionally, discussions include the identification of cell phenotypes and the exploration of the novel concept of innate immunity possibly possessing memory.

Assessment of inspiration and technical quality in anteroposterior thoracic radiographs using machine learning.

INTRODUCTION: Chest radiographs are the most performed radiographic procedure, but suboptimal technical factors can impact clinical interpretation. A deep learning model was developed to assess technical and inspiratory adequacy of anteroposterior chest radiographs. METHODS: Adult anteroposterior chest radiographs (n = 2375) were assessed for technical adequacy, and if otherwise technically adequate, for adequacy of inspiration. Images were labelled by an experienced radiologist with one of three ground truth labels: inadequate technique (n = 605, 25.5 %), adequate inspiration (n = 900, 37.9 %), and inadequate inspiration (n = 870, 36.6 %). A convolutional neural network was then iteratively trained to predict these labels and evaluated using recall, precision, F1 and micro-F1, and Gradient-weighted Class Activation Mapping analysis on a hold-out test set. Impact of kyphosis on model accuracy was assessed. RESULTS: The model performed best for radiographs with adequate technique, and worst for images with inadequate technique. Recall was highest (89 %) for radiographs with both adequate technique and inspiration, with recall of 81 % for images with adequate technique and inadequate inspiration, and 60 % for images with inadequate technique, although precision was highest (85 %) for this category. Per-class F1 was 80 %, 81 % and 70 % for adequate inspiration, inadequate inspiration, and inadequate technique respectively. Weighted F1 and Micro F1 scores were 78 %. Presence or absence of kyphosis had no significant impact on model accuracy in images with adequate technique. CONCLUSION: This study explores the promising performance of a machine learning algorithm for assessment of inspiratory adequacy and overall technical adequacy for anteroposterior chest radiograph acquisition. IMPLICATIONS FOR PRACTICE: With further refinement, machine learning can contribute to education and quality improvement in radiology departments.

The effects of priming on rhinologic patient reported outcome measures: a randomized controlled trial.

BACKGROUND: Patient-reported outcome measures (PROMs) are questionnaires designed to assess a patient's perception of their medical condition. The 22-item Sino-Nasal Outcomes Test (SNOT-22), the Rhinosinusitis Disability Index (RSDI) and the mini-Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) are validated PROMs commonly used to assess rhinologic conditions. The objective of this study is to determine if responses on these PROMs may be influenced by priming respondents with positive or negative health-related questionnaires. METHODS: Nine hundred patients were prospectively randomized to one of nine groups. Groups A, D and G were positively primed prior to completing the SNOT-22, the RSDI and MiniRQLQ, respectively. Groups B, E, and H were negatively primed. Groups C, F, and I served as control groups, completing the PROMs without priming. Priming was performed by administering a survey designed to make patients think about their health-related quality of life in a positive or negative way. RESULTS: Patients who were primed negatively had statistically significantly worse scores on the SNOT-22, RSDI and MiniRQLQ when compared to patients who were primed positively. When compared to the control group, patients who were primed negatively had statistically worse scores on the SNOT-22 and RSDI. There was no significant difference in scores between the positive priming and the control groups for any PROM. CONCLUSIONS: Priming subjects regarding their health-related quality of life impacts their responses on rhinologic PROMs. Further study is required to understand the clinical and research implications of this novel finding and to clarify the optimal manner for administering and interpreting PROMs.

[Epidemiological and clinical characteristics of human ocular helaziasis in China from 2011 to 2022 based on bibliometrics].

OBJECTIVE: To understand the clinical and epidemiological characteristics of human ocular thelaziasis patients in China. METHODS: Case reports regarding human ocular thelaziasis cases in China were retrieved in international and national electronic databases, including CNKI, VIP, CBM, Traditional Chinese Medical Literature Analysis and Retrieval System, Wanfang Database, PubMed and Web of Science from 2011 to 2022. Patients' gender, age, clinical symptoms, treatment, recurrence, site of infections, time of onset, affected eye, affected sites, number of infected Thelazia callipaeda, sex of T. callipaeda and source of infections were extracted for descriptive analyses. RESULTS: A total of 85 eligible publications were included, covering 101 cases of human ocular thelaziasis, including 57 males (56.44%) and 44 females (43.56%) and aged from 3 months to 85 years. The main clinical manifestations included foreign body sensation (56 case-times, 22.49%), eye itching (38 case-times, 15.26%), abnormal or increased secretions (36 case-times, 14.46%), tears (28 case-times, 11.24%) and eye redness (28 case-times, 11.24%), and conjunctival congestion (50 case-times, 41.67%) was the most common clinical sign. The most common main treatment (99/101, 98.02%) was removal of parasites from eyes using ophthalmic forceps, followed by administration with ofloxacin and pranoprofen. In publications presenting thelaziasis recurrence, there were 90 cases without recurrence (97.83%) and 2 cases with recurrence (2.17%). Of all cases, 51.96% were reported in four provinces of Hubei, Shandong, Sichuan, Hebei and Henan, and ocular thelaziasis predominantly occurred in summer (42.19%) and autumn (42.19%). In addition, 56.45% (35/62) had a contact with dogs. CONCLUSIONS: The human thelaziasis cases mainly occur in the continental monsoon and subtropical monsoon climate areas such as the Yellow River and the Yangtze River basin, and people of all ages and genders have the disease, with complex clinical symptoms and signs. Personal hygiene is required during the contact with dogs, cats and other animals, and individual protection is required during outdoor activities to prevent thelaziasis.

[High expression of ANKRD6 is an indicator for poor prognosis of colon adenocarcinoma].

OBJECTIVE: To explore the expression of ANKRD6 in colon adenocarcinoma (COAD) and its implications for prognosis and treatment of COAD. METHODS: We investigated the differential expression of ANKRD6 in 20 pairs of COAD and adjacent tissues using immunohistochemistry and in colon cancer cell lines and normal colon cells using real-time quantitative PCR. Gene expression matrices, immune infiltration data, and clinical information of 521 COAD patients and 41 normal tissues were obtained from the TCGA database for analyzing the association of ANKRD6 expression with clinicopathological features, gene set enrichment, and immune infiltration in COAD using R software. The prognostic factors of COAD were evaluated using univariate and multivariate Cox regression and Kaplan-Meier analyses, and a prognostic nomogram containing ANKRD6 was constructed. Western blotting, CCK-8 assay, scratch assay and Transwell assay were performed to assess the effects of ANKRD6 knockdown on biological activities of COAD cells. RESULTS: ANKRD6 was highly expressed in COAD cell lines and upregulated in COAD tissues with higher malignancy (P<0.05). Increased ANKRD6 expression was significantly correlated with decreased overall survival and disease-free survival of COAD patients (P<0.05). Univariate and multivariate Cox regression analyses indicated that ANKRD6 expression was significantly correlated with the overall survival rate of COAD patients (P<0.05). The constructed prognostic nomogram showed a C-index value of 0.739 and effectively predicted the 1-, 3-, and 5-year survival of the patients. ANKRD6 expression was positively correlated with immune infiltration of macrophages (P<0.05) and negatively correlated with Th17 cells and other immune cell infiltration (P<0.05). Bioinformatic analysis suggested that ANKRD6 was mainly enriched in Wnt, vascular endothelial growth factor receptor, and calcium signaling pathways in COAD. In cultured COAD cells, ANKRD6 knockdown significantly suppressed cell proliferation, migration, and invasion (P<0.05). CONCLUSION: High ANKRD6 expression is an indicator for poor prognosis of COAD, and ANKRD6 may serve as a potential biomarker as well as a therapeutic target for diagnosis and treatment of COAD.

[Association between obstructive sleep apnea and vascular injury in hypertensive patients].

Objective: To investigate the relationship between obstructive sleep apnea (OSA), apnea hypopnea index (AHI) and vascular injury in hypertensive patients. Methods: This cross-sectional study enrolled patients admitted to the Hypertension Department of TEDA International Cardiovascular Hospital from April 2020 to April 2023, who finished portable sleep monitoring. Sleep monitoring indicators, flow-mediated vasodilation (FMD), carotid artery ultrasound, carotid intima-media thickness, cervical and femoral pulse wave conduction velocity (cfPWV), brachial and ankle pulse wave conduction velocity (baPWV) were analyzed. OSA was classified into mild (5 times/h≤AHI<15 times/h), moderate (15≤AHI<30 times/h), and severe (AHI≥30 times/h) based on AHI levels. FMD<6.0% was defined as vascular endothelial injury, and cfPWV>10 m/s and/or baPWV>18 m/s was defined as arterial stiffness. Multivariate logistic regression analysis was used to explore the correlation between AHI, OSA severity and vascular injury, and subgroup analysis was performed in young (age≤45 years) and middle-to-old patients (age>45 years). Sensitivity analysis was performed by excluding patients with diabetes, cerebrovascular disease and coronary heart disease. The correlation between AHI and vascular injury index was analyzed by restricted cubic spline. Results: A total of 555 adult hypertensive patients were included, the mean age was (39.7±9.2) years, 422 were males (76.0%), and the prevalence of OSA was 66.7% (370/555). Multivariate logistic regression analysis showed that moderate OSA (OR=2.83, P=0.019) and severe OSA (OR=3.40, P=0.016) were positively correlated with vascular endothelial injury after adjusting for age, sex, body mass index and mean arterial pressure. Subgroup analysis showed that log AHI (OR=1.99, P=0.035), moderate OSA (OR=4.83, P=0.010) and severe OSA (OR=4.64, P=0.015) were associated with vascular endothelial injury in young hypertensive patients. The results of sensitivity analysis were similar to the above results. The results of restricted cubic spline analysis showed that AHI was correlated with FMD (P=0.022), and the slope of the curve was the largest when AHI was between 0 and 10 times/h. There was no correlation between log AHI and OSA severity and carotid intima-media thickening and arterial stiffness (all P<0.05). Conclusions: OSA is associated with vascular endothelial injury in hypertensive patients, especially in young patients.

High Dietary Zinc Intake Is Associated with Shorter Leukocyte Telomere Length, Mediated by Tumor Necrosis Factor-α: A Study of China Adults.

OBJECTIVES: Diet can influence peripheral leukocyte telomere length (LTL), and various micronutrients have been reported to correlate with it. Zinc is known for its antioxidant properties and immunomodulatory effects. However, there are few epidemiological investigations on the relationship between dietary zinc intake and LTL. This study analyzed the association between dietary zinc and LTL and the potential role of inflammation and oxidative stress among them. DESIGN: Cross-sectional and community-based study. SETTING AND PARTICIPANTS: 599 participants from rural communities in the Changping suburb of Beijing, China, were recruited. MEASUREMENTS: Serum lipid profile, glycosylated hemoglobin (HbA1c), oxidative stress marker, and inflammatory cytokines levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Spearman analysis, restricted cubic splines (RCS), and general linear regression models were used to determine the association between dietary zinc intake and LTL. Simple regulatory models were also applied to analyze the role of inflammation and oxidative stress among them. RESULTS: A total of 482 subjects were ultimately included in this analysis. Spearman analysis showed that dietary zinc intake and zinc intake under energy density were negatively correlated with LTL (r=-0.142 and -0.126, all P <0.05) and positively correlated with tumor necrosis factor-α (TNF-α) (r=0.138 and 0.202, all P <0.05) while only dietary zinc without energy adjustment had a positive correlation with superoxide dismutase (SOD). RCS (P for non-linearity=0.933) and multiple linear regression (B=-0.084, P=0.009) indicated a negative linear association between dietary zinc and LTL. The adjustment of TNF-α rather than SOD could abolish the relationship. The mediation model suggested that the unfavorable effect of dietary zinc on LTL was mediated by TNF-α. CONCLUSIONS: High dietary zinc may correlate with telomere attrition, and TNF-α can act as a mediator in this relationship. In the future, more extensive cohort studies are needed to further explore the relationship between dietary zinc and cellular aging and the specific mechanisms.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Multitrait meta-analyses identify potential candidate genes for growth-related traits in Holstein heifers.

Understanding the underlying pleiotropic relationships among growth and body size traits is important for refining breeding strategies in dairy cattle for optimal body size and growth rate. Therefore, we performed single-trait GWAS for monthly-recorded body weight (BW), hip height, body length, and chest girth from birth to 12 mo of age in Holstein animals, followed by stepwise multiple regression of independent or lowly-linked markers from GWAS loci using conditional and joint association analyses (COJO). Subsequently, we conducted a multitrait meta-analysis to detect pleiotropic markers. Based on the single-trait GWAS, we identified 170 significant SNPs, in which 59 of them remained significant after the COJO analyses. The most significant SNP, located at BTA7:3,676,741, explained 2.93% of the total phenotypic variance for BW6 (BW at 6 mo of age). We identified 17 SNPs with potential pleiotropic effects based on the multitrait meta-analyses, which resulted in 3 additional SNPs in comparison to those detected based on the single-trait GWAS. The identified quantitative trait loci regions overlap with genes known to influence human growth-related traits. According to positional and functional analyses, we proposed HMGA2, HNF4G, MED13L, BHLHE40, FRZB, DMP1, TRIB3, and GATAD2A as important candidate genes influencing the studied traits. The combination of single-trait GWAS and meta-analyses of GWAS results improved the efficiency of detecting associated SNPs, and provided new insights into the genetic mechanisms of growth and development in Holstein cattle.

[Spatial correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in a typical coal-fired pollution fluorosis area].

Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.