Associations and Potential Multiple Mechanisms between Subjective Hearing Loss and Cognitive Impairment.

BACKGROUND: Subjective hearing loss (SHL) refers to an individual's self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation. OBJECTIVES: To validate potential mechanisms between SHL and cognitive impairment. DESIGN: Cross-section. SETTING: Shanghai, China. PARTICIPANTS: A total of 2369 individuals from communities and the cognitive disorder clinic. MEASUREMENTS: All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants' brain ß-amyloid (Aß) deposition status, plasma biomarkers associated with Alzheimer's disease (AD), and cardiovascular risk factors were also collected. RESULTS: In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aß deposition, SHL demonstrated associations with cognitive function independent of plasma Aß42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status. CONCLUSION: SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.

[Comorbidity of anxiety symptoms and depression symptoms among middle and high school students in Zhejiang Province].

Objective: To analyze the epidemiological patterns of comorbidity of anxiety symptoms and depression symptoms among middle and high school students in Zhejiang Province and to provide evidence for making strategy and evaluation of intervention. Methods: Through a multi-stage sampling design, 28 043 students from 376 schools in 30 counties/districts were recruited and surveyed using anonymous self-administered questionnaires in classrooms under the supervision of trained staff between April and June 2022. Anxiety symptoms were assessed using generalized Anxiety Disorders 7-Item Scale, and depression symptoms were assessed using Patient Health Questionnaire 9-Item Depression Scale. A total of 27 004 students were included in the final analysis. Results: The overall prevalence of comorbidity of anxiety symptoms and depression symptoms was 11.54% (95%CI: 10.90%-12.19%), higher among girls (15.42%, 95%CI: 14.47%- 16.38%) than boys (8.05%, 95%CI: 7.43%-8.67%) (P<0.001), higher among students living in rural areas (12.35%, 95%CI: 11.49%-13.22%) than those in urban areas (10.06%, 95%CI: 9.27%-10.86%) (P<0.001). The prevalence of comorbidity of students attending middle school, academic high school, and vocational high school was 11.73% (95%CI: 10.82%-12.64%), 12.49% (95%CI: 11.20%- 13.79%), and 9.98% (95%CI: 8.68%-11.27%), respectively (P=0.025). The prevalence of comorbidity was higher among students in divorced/widow/separated families (16.64%, 95%CI: 14.86%-18.43%) than those in intact families (10.82%, 95%CI: 10.14%-11.50%) (P<0.001). The wealthier the families, the lower the prevalence of comorbidity (P<0.001). The prevalence of comorbidity was higher among cigarettes smokers in the past 30 days (21.70%,95%CI: 18.24%- 25.16%) than non-smokers (11.13%, 95%CI: 10.51%-11.76%), higher among alcohol drinkers in the past 30 days (19.36%, 95%CI: 17.58%-21.14%) than non-drinkers (10.05%, 95%CI: 9.43%- 10.68%), higher among students engaging in physical fight in the past 12 months (18.42%, 95%CI: 16.75%-20.09%) than those without physical fight (10.45%, 95%CI: 9.81%-11.10%). The more frequently students engaged in physical exercise, the lower the prevalence of comorbidity (P<0.001). The poorer the academic performance self-reported, the higher the prevalence of comorbidity (P<0.001). Conclusion: More than one-tenth of middle and high school students in Zhejiang Province have comorbidity of anxiety symptoms and depression symptoms, and more attention should be paid to adolescent mental health.

[Efficacy and short-term outcomes of myocardial protection using single-dose histidine-tryptophan-ketoglutarate cardioplegia during aortic root surgery with different duration of myocardial ischemia].

Objective: To explore the efficacy of myocardial protection with single-dose histidine-tryptophan-ketoglutarate (HTK) cardioplegia during aortic root operation, and the correlation between short-term clinical outcomes and duration of myocardial ischemia. Methods: The data of clinical cases undergoing myocardial protection with single-dose HTK cardioplegia during aortic root operation from January 2018 to December 2022 were retrospectively reviewed. Patients were divided into conventional HTK cardioplegia group (<3 h) and prolonged HTK cardioplegia group (≥3 h) according to duration of intraoperative myocardial ischemia. A 1∶1 propensity score matching was performed and the correlations between duration of myocardial ischemia and postoperative short-term outcomes (30-day mortality, readmission, mechanical circulation support and renal insufficiency) were analyzed. Results: A total of 282 patients were included in the final analysis, with 210 cases in the conventional HTK cardioplegia group and 72 cases inthe prolonged HTK cardioplegia group before matching. After matching, there were 64 cases (53 males and 11 females) in the conventional HTK cardioplegia group, with a mean age of (49.4±14.2) years. The prolonged HTK cardioplegia group had 64 cases (55 males and 9 females), with a mean age of (50.5±12.3) years. Higher sensitivity troponin [12 h: 10.1 (4.6, 18.7) µg/Lvs 4.1(2.2, 8.6) µg/L, P=0.002; 24 h: 7.7 (4.5, 19.0) µg/L vs 4.8 (2.2, 11.9) µg/L, P=0.025] and creatine kinase isoenzyme[12 h: 46.3 (28.1, 62.4) µg/L vs 20.7(14.1, 32.9) µg/L, P<0.001; 24 h: 26.3(13.4, 49.2) µg/L vs 14.5 (10.1, 33.5)µg/L, P=0.011] after surgery was detected in prolonged HTK cardioplegia group. Comparisons of other primary and secondary endpoint events showed no significant differences between the two groups (all P>0.05). Multivariate binary logistic regression showed that duration of myocardial ischemia had no significant effect on postoperative 30-day mortality (OR=1.255, 95%CI: 0.500-3.148, P=0.629), 30-day readmission (OR=0.378, 95%CI: 0.069-2.065, P=0.261) and mechanical circulation support (OR=0.991, 95%CI: 0.331-2.970, P=0.998). Conclusion: During aortic root surgery, single-dose HTK cardioplegia may provide satisfactory myocardial protection, and there was no significant correlation between duration of myocardial ischemia and short-term clinical outcomes.

[The prevalence of insufficient physical activity and the influencing factors among Chinese adults in 2018].

Objective: To understand the prevalence of insufficient physical activity among adults aged ≥18 years in China and to explore the influencing factors. Methods: The China Chronic Disease and Risk Factor Surveillance was conducted in 298 counties/districts in China in 2018, covering 31 provinces (autonomous regions, municipalities). A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. A questionnaire including Global Physical Activity Questionnaire was used to collect information about the participants' demographic characteristics and physical activity through face-to-face interview. A total of 183 769 participants completed the survey. After complex data weighting, the prevalence of insufficient physical activity, occupation, transportation, and leisure-time physical activity time was analyzed. Multivariate logistic regression models were used to analyze the influencing factors related to insufficient physical activity. Results: The prevalence of insufficient physical activity among adults aged ≥18 years was 22.3% (95%CI: 20.9%-23.7%) in China in 2018, with males [24.4% (95%CI: 23.0%-25.8%)] significantly higher than females [20.2% (95%CI: 18.6%-21.8%)]. Adults aged 70 years and above [28.4% (95%CI: 26.9%-29.9%)] were significantly higher than adults in other age groups, followed by adults aged 18-29 years [26.4% (95%CI: 24.4%- 28.3%)] and 30-39 years [23.4% (95%CI: 21.5%-25.3%)], and tended to increase with increasing education and total sedentary behavior time (P<0.001). The weekly occupation, transportation, and leisure-time physical activity time appeared 958.6 (95%CI: 911.4-1 005.8) minutes, 234.5 (95%CI: 224.7- 244.2) minutes, and 88.6 (95%CI: 83.5-93.7) minutes, respectively. Multivariate logistic regression analysis showed that males, adults living in rural areas or northern China, ≥70 years, with junior high school education, an annual household income per capita <6 000 yuan and institutional/clerical/ technical occupation and longer total sedentary behavior time were related to a higher prevalence of insufficient physical activity. Conclusions: In China, over one-fifth of the adults had lower physical activity levels. Adults who are male, young adults, more educated, institutional/clerical/technical occupation, and with more extended total sedentary behavior are the populations that need to be focused on to promote physical activity-related health.

[Investigation and factor analysis of postoperative surgical site infections in emergency abdominal surgery in China from 2018 to 2021 based on Chinese SSI Surveillance].

Objective: We investigated the incidence of surgical site infection (SSI) following emergency abdominal surgery (EAS) in China and further explored its risk factors, providing a reference for preventing and controlling SSI after EAS. Methods: This was an observational study. Data of patients who had undergone EAS and been enrolled in the Chinese SSI Surveillance Program during 2018-2021were retrospectively analyzed. All included patients had been followed up for 30 days after surgery. The analyzed data consisted of relevant patient characteristics and perioperative clinical data, including preoperative hemoglobin, albumin, and blood glucose concentrations, American Society of Anesthesiologists (ASA) score, grade of surgical incision, intestinal preparation, skin preparation, location of surgical site, approach, and duration. The primary outcome was the incidence of SSI occurring within 30 days following EAS. SSI was defined as both superficial and deep incisional infections and organ/space infections, diagnoses being supported by results of microbiological culture of secretions and pus. Secondary outcomes included 30-day postoperative mortality rates, length of stay in the intensive care unit (ICU), duration of postoperative hospitalization, and associated costs. The patients were classified into two groups, SSI and non-SSI, based on whether an infection had been diagnosed. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with SSI following EAS. Results: The study cohort comprised 5491 patients who had undergone EAS, comprising 3169 male and 2322 female patients. SSIs were diagnosed in 168 (3.1%) patients after EAS (SSI group); thus, the non-SSI group consisted of 5323 patients. The SSIs comprised superficial incision infections in 69 (41.1%), deep incision infections in 51 (30.4%), and organ or space infections in 48 (28.6%). Cultures of secretions and pus were positive in 115 (68.5%) cases. The most frequently detected organism was Escherichia coli (47/115; 40.9%). There were no significant differences in sex or body mass index between the SSI and non-SSI groups (both P>0.05). However, the proportion of individuals aged 60 years or older was significantly greater in the SSI than in the non-SSI group (49.4% [83/168] vs. 27.5% [1464/5323), χ2=38.604, P<0.001). Compared with the non-SSI group, the SSI group had greater proportions of patients with diabetes (11.9% [20/168] vs. 4.8% [258/5323], χ2=16.878, P<0.001), hypertension (25.6% [43/168] vs. 12.2% [649/5323], χ2=26.562, P<0.001); hemoglobin <110 g/L (27.4% [46/168] vs. 13.1% [697/5323], χ2=28.411, P<0.001), and albuminemia <30 g/L (24.4% [41/168] vs. 5.9% [316/5323], χ2=91.352, P<0.001), and a reduced rate of preoperative skin preparation (66.7% [112/168] vs. 75.9% [4039/5323], χ2=7.491, P=0.006). Furthermore, fewer patients in the SSI group had preoperative ASA scores of between one and two (56.0% [94/168] vs. 88.7% [4724/5323], χ2=162.869, P<0.001) in the non-SSI group. The incidences of contaminated and infected incisions were greater in the SSI group (63.1% [106/168] vs. 38.6% [2056/5323], χ2=40.854, P<0.001). There was a significant difference in surgical site distribution between the SSI and non-SSI groups (small intestine 29.8% [50/168] vs. 10.6% [565/5323], colorectal 26.2% [44/168] vs. 5.6% [298/5 323], and appendix 24.4% [41/168] vs. 65.1% [3465/5323]) χ2=167.897, P<0.001), respectively. There was a significantly lower proportion of laparoscope or robotic surgery in the non-SSI group (24.4 % [41/168] vs. 74.2% [3949/5323], χ2=203.199, P<0.001); the percentage of operations of duration less than 2 hours was significantly lower in the SSI than non-SSI group (35.7% [60/168] vs. 77.4% [4119/5323], χ2=155.487, P<0.001). As to clinical outcomes, there was a higher 30-day postoperative mortality rate (3.0%[5/168] vs. 0.2%[10/5323], χ2=36.807, P<0.001) and higher postoperative ICU occupancy rate (41.7% [70/168] vs. 19.7% [1046/5323], χ2=48.748, P<0.001) in the SSI group. The median length of stay in the ICU (0[2] vs. 0[0] days, U=328597.000, P<0.001), median total length of stay after surgery (16[13] vs. 6[5] days, U=128146.000, P<0.001), and median hospitalization cost (ten thousand yuan, 4.7[4.4] vs. 1.7[1.8], U=175965.000, P<0.001) were all significantly greater in the SSI group. Multivariate logistic regression analysis revealed that the absence of skin preparation before surgery (OR=2.435,95%CI: 1.690-3.508, P<0.001), preoperative albuminemia <30 g/L (OR=1.680, 95%CI: 1.081-2.610, P=0.021), contaminated or infected incisions (OR=3.031, 95%CI: 2.151-4.271, P<0.001), and laparotomy (OR=3.436, 95% CI: 2.123-5.564, P<0.001) were independent risk factors of SSI. Operative duration less than 2 hours (OR=0.465, 95%CI: 0.312-0.695, P<0.001) and ASA score of 1-2 (OR=0.416, 95% CI: 0.289-0.601, P<0.001) were identified as independent protective factors for SSI. Conclusions: It is important to consider the nutritional status in the perioperative period of patients undergoing EAS. Preoperative skin preparation should be conducted and, whenever possible, laparoscope or robot-assisted surgery. Duration of surgery should be as short as possible while maintaining surgery quality and improving patient care.

[The effect of unexpected follicular development in artificial cycles on the clinical outcomes in frozen thawed embryo transfer based on propensity score matching].

Objective: To study the effect of unexpected follicular development in artificial cycles on the clinical outcomes in frozen thawed embryo transfer based on propensity score matching(PSM). Methods: The retrospective cohort study analyzed the clinical data of 7 064 cycles (5 716 patients) of artificial cycle frozen-thawed embryo transfer (AC-FET) in the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2016 to December 31, 2020. The clinical data were divided into three groups according to the degree of follicular development in AC-FET: no follicular growth group (group A, 6 349 cycles), small follicular growth group (group B, 248 cycles), and large follicular growth group (group C, 467 cycles). Differences in clinical outcomes between the small follicle growth group (Group B) and the large follicle growth group (Group C) were compared with the no follicle growth group (Group A) after PSM and logistic regression to adjust for confounding factors at baseline. A binary logistic regression model was used to analyze the factors related to the unanticipated follicular development in AC-FET. Results: Age [M(Q1,Q3)] was [31.0 (28.0, 36.0)] years in Group A, [34.5 (30.0, 40.0)] years in Group B, and [36.0 (31.0, 41.0)] years in Group C. After adjusting for confounders, the differences between Groups A and B in clinical pregnancy rate (P=0.169), live birth rate (P=0.318), early abortion rate (P=0.470), and miscarriage rate (P=0.783) were not statistically significant. The differences in clinical pregnancy rate (P=0.743), live birth rate (P=0.486) and miscarriage rate (P=0.080) between Groups A and C were not statistically significant, while early miscarriage rate (P=0.034) differences were statistically significant. The age, BMI, basal AFC, AMH and starting dose of estrogen were correlates of the emergence of non-expected small follicles in Groups B and A. The adjusted OR (AOR) values (95%CI) were 1.03 (1.01-1.06), 0.93 (0.90-0.98), 0.97 (0.95-0.99), 0.96 (0.95-0.97), and 0.59 (0.45-0.77), all P<0.05. Age, basal AFC, AMH and starting dose of estrogen were the associated factors of the appearance of non-expected large follicles in Groups C and A. The AOR values (95%CI) were 1.03 (1.01-1.05), 0.93 (0.91-0.95), 0.96 (0.95-0.97), and 0.52 (0.42-0.64), all P<0.05. Conclusions: In AC-FET, the clinical outcome of small follicular growth is similar to that of unfollicular growth; Compared with the growth without follicles, the growth and development of large follicles can reduce the early abortion rate; Patients with older age, less AFC, lower AMH, and lower initial dose of estrogen could be more likely to have unanticipated follicular development during endometrial preparation.

[Effect of preimplantation genetic testing for aneuploidies on pregnancy outcome in patients with unexplained recurrent spontaneous abortion].

Objective: To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) on pregnancy outcome and perinatal outcome of single live birth in patients with unexplained recurrent spontaneous abortion (URSA). Methods: The clinical data of 351 cycles of the first transfer of a blastocyst through whole embryo freezing in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from 2019 to 2021 were retrospectively analyzed. According to whether PGT-A was performed before the transfer, the patients were divided into two groups: the PGT-A group (160 cycles) and the control group (191 cycles) were treated with in vitro fertilization/intracytoplasmic sperm microinjection (IVF/ICSI). To adjust for confounding factors, propensity score matching (PSM) was carried out in a 1∶1 ratio between the two groups of patients. After matching, 98 patients in the PGT-A group and 98 patients in the control group were compared for pregnancy outcome and perinatal outcome of singleton live births. Results: Before PSM, the female age in the PGT-A group was (33.6±4.0) years, lower than that in the control group (34.5±4.5) years (P=0.049). Male age in the PGT-A group was (33.6±4.1) years, lower than that in the control group (35.3±5.1) years (P<0.001). There were statistically significant differences between the two groups in infertility factors, female body mass index (BMI), years of infertility, number of spontaneous abortions, basal follicle stimulating hormone (FSH), endometrial thickness on the day of transfer and the percentage of high-quality blastocysts (all P values<0.05); After PSM, there was a statistically significant difference in fertilization methods and infertility factors between the two groups (P<0.05), while other differences were not statistically significant (all P values>0.05); There were statistically significant differences between the two groups in implant rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], clinical pregnancy rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], and live birth rate [42.9% (42 cycles) vs. 28.6% (28 cycles), P=0.037]. There was no statistically significant difference in perinatal outcomes between the PGT-A group and the control group in obtaining single birth live births (P>0.05). Conclusion: Compared with conventional IVF/ICSI assisted pregnancy, PGT-A assisted pregnancy significantly improves implantation rate, clinical pregnancy rate, and live birth rate in URSA patients. PGT-A improves the pregnancy outcomes in URSA patients but not perinatal outcomes in patients with singleton live births.

[The effect of chronic endometritis on the clinical outcomes of patients with failure of first embryo transfer].

Objective: To investigate the effect of chronic endometritis (CE) on the clinical outcomes of patients with failure of first embryo transfer. Methods: A total of 5 605 cycles of frozen-thawed single blastocyst transfer in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to June 2021 were retrospectively collected. After the failure of first embryo transfer, all patients underwent hysteroscopy, and when necessary, endometrial pathology and immunohistochemistry were combined to diagnose CE. Patients were divided into two groups: non-CE group (5 033 cycles) and CE treatment group (572 cycles). The main outcome was live birth rate and the secondary outcomes included clinical pregnancy rate and early abortion rate. The quantitative data were represented by Median (Q1, Q3). The rank sum test was used for comparison between groups. The factors related to live birth rate were analyzed by binary logistic regression model. Results: The incidence of CE was 10.21% (572 cycles) in patients with the failure of first embryo transfer. The maternal age in the non-CE group was 31.0 (29.0, 34.0) years old, and that in the CE treatment group was 31.0 (29.0, 34.0) years old (P<0.001). There was a statistically significant difference in endometrial preparation between the two groups (P=0.010). The endometrial thickness in the CE group was 9.0 (8.2, 10.3) mm on progesterone transformation day, which was higher than that of [9.5 (8.6, 11.0) mm] in the non-CE group (P<0.001). There was no significant difference in clinical pregnancy rate (60.3% (3 035 cycles) vs 63.1% (361 cycles), P=0.193), early abortion rate (17.1% (520 cycles) vs 20.5% (74 cycles), P=0.112) and live birth rate (49.2% (2 477 cycles) vs 49.3% (282 cycles), P=0.969) between the non-CE group and the CE treatment group. The maternal age, endometrial thickness on progesterone transformation day and blastocyst grade were related factors of the live birth rate, and the OR(95%CI) were 0.94 (0.93-0.96), 1.10 (1.06-1.14) and 2.07 (1.84-2.32)), respectively (all P<0.001). Compared with the non-CE group, the CE treatment group did not affect the live birth rate after transplantation, the aOR (95%CI) was 0.99 (0.82-1.18), P=0.882. Conclusions: For patients who underwent the failure of first embryo transfer, hysteroscopy is recommended before single frozen blastocyst transfer, and if necessary, combined with immunohistochemical screening for CE. After standardized treatment, CE patients could obtain similar clinical pregnancy rate, early miscarriage rate and live birth rate as non-CE patients.

[The effects of high risk of ovarian hyperstimulation syndrome and duration of embryo cryopreservation on perinatal outcomes of single live births in the first frozen embryo transfer cycle after whole embryo cryopreservation].

Objective: To investigate the effects of high risk of ovarian hyperstimulation syndrome (OHSS) and duration of embryo cryopreservation on perinatal outcomes of the first frozen-thawed cycle after whole embryo cryopreservation. Methods: The clinical data of 1 804 patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation and achieved singleton live births in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to June 2021 were retrospectively analyzed. According to whether there was high risk of OHSS in the oocyte retrieval cycle, the patients were divided into high-risk group (n=790) and non-high-risk group (n=1 014). The baseline data and perinatal outcomes were compared between the two groups. Multivariate linear regression was applied to analyze the relative factors affecting neonatal weight. And the high-risk group was divided into three subgroups according to different cryopreservation time: the embryos of 96 cycles with a cryopreservation time less than 60 days were defined as group A; the embryos of 587 cycles with a cryopreservation time around 60 to 120 days were defined as group B; the embryos of 107 cycles with a cryopreservation time more than 120 days were defined as group C. The perinatal outcomes were compared among the three groups. The measurement data in this study were represented byï¼»M（Q1，Q3）］. Results: The female age in the high-risk group was 30.0 (27.0, 32.0) years old, which was lower than that in the non-high-risk group 31.0 (29.0, 34.0) (P<0.001). The male age in high-risk group was 30.0 (28.0, 33.0), lower than that in non-high-risk group 32.0 (29.0, 35.0) (P<0.001). The birth weight of high-risk group [3 500.0 (3 200.0,3 800.0) g] was higher than that of control group [3 400.0 (3 150.0,3 800.0) g](P=0.045). Multivariate linear regression analysis showed that female BMI was correlated with neonatal weight, ß (95%CI) was 15.37(8.33, 22.41) (P<0.001), and the high risk of OHSS was not correlated with neonatal weight, ß (95%CI) was 19.40 (-38.07, 76.87) (P=0.508). There was significant difference in the incidence of low birth weight and very low birth weight among groups A, B and C (all P values<0.05), and the incidence of low birth weight and very low birth weight in group C was higher than that in group B (all P values<0.017). Conclusions: The risk of adverse perinatal outcomes in high-risk OHSS patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation was not increased. However, prolonged cryopreservation of embryos may lead to increased risk of low birth weight and very low birth weight.

Chinese Preclinical Alzheimer's Disease Study (C-PAS): Design and Challenge from PET Acceptance.

BACKGROUND: Large-scale preclinical Alzheimer's disease study based on ß-amyloid positron emission tomography (PET) has not been conducted in China. OBJECTIVES: Establish a cohort on Alzheimer's disease spectrum, especially the preclinical stages, and determine the factors influencing the acceptance of ß-amyloid PET scan screening in China. DESIGN: Longitudinal. SETTING: Shanghai, China. PARTICIPANTS: A total of 4386 participants were screened and 2451 participants who met enrollment criteria were eventually included in this report. MEASUREMENTS: The multidimensional data was collected, including comprehensive assessments, PET and magnetic resonance imaging scans, genetics, and plasma biomarkers. RESULTS: There were 571 participants in the normal cognition group, 625 participants in the subjective cognitive decline group, 155 participants in the objectively defined subtle cognitive decline group, 501 participants in the mild cognitive impairment group, 471 participants in Alzheimer's disease group, and 128 participants with cognitive impairment from other known causes. Significant differences in demographics, florbetapir PET, APOE, and neuropsychological tests were found among the groups. Eight hundred and seventeen participants (33.3%) completed the florbetapir PET scanning. Non-demented individuals with higher age, lower education years, male, with a family history of dementia, and higher self-report depression prefer to undergo PET scans. Acceptance of PET scans did not correlate with objectively assessed cognitive impairment. CONCLUSIONS: The Chinese Preclinical Alzheimer's Disease Study was designed to establish a large-scale cohort with comprehensive data collection. Our findings may help to understand the factors affecting the acceptance of ß-amyloid PET in urban areas of China and help us address the low acceptance challenge.

[Efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitors treatment failure].

Objective: To investigate the efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer (NSCLC) who failed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: A retrospective analysis was made on the clinical data of 60 NSCLC patients who were treated with immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure in the Affiliated Cancer Hospital of Shandong First Medical University from January 2019 to March 2022. Patients were followed up by telephone or outpatient review up to October 1, 2022, with a median follow-up of 8.2 months (95%CI: 7.1-9.3). All 60 patients were followed up. The response evaluation criteria in solid tumors were used to evaluate the short-term efficacy. The adverse reactions of patients were evaluated according to the common terminology criteria for adverse events. The survival curve was drawn by Kaplan-Meier method. Cox proportional hazard regression models were utilized to analyze the influencing factors of progression-free survival (PFS). Results: Among the 60 NSCLC patients, 22 were males. The age ranged from 41 to 75 years, with a median age of 61 years. Eleven patients had partial response, 19 patients had stable disease and 30 patients had progressive disease. The median PFS was 8.2 months (95%CI: 7.2-9.2). The median PFS of patients with low expression of programmed death receptor-ligand 1 (PD-L1) [Tumor cell Proportion Score (TPS)<1%], moderate expression of PD-L1 (1%≤TPS≤49%), and high expression of PD-L1 (TPS≥50%) were 6.4 (95%CI: 4.8-8.0), 8.3 (95%CI: 7.3-9.3) and 10.6 months (95%CI: 7.2-14.1), respectively, and there were statistically significant differences (χ2=13.58, P<0.001). Multivariate Cox proportional risk regression model analysis showed that age>65 years old (HR=4.017, 95%CI: 1.468-10.992, P=0.007) was a risk factor for PFS in NSCLC patients who received immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure. Moderate expression of PD-L1 (HR=0.360, 95%CI: 0.139-0.930, P=0.035) and high expression of PD-L1 (HR=0.155, 95%CI: 0.039-0.625, P=0.009) were protective factors for PFS. Most of the treatment-related adverse reactions in the whole group were grade 1-2, including bone marrow suppression (n=24), nausea (n=25), decreased appetite (n=24), fatigue (n=22), vomiting (n=18), abnormal liver function (n=17), blood creatinine increased (n=10), and so on. These were tolerated by the patients. Conclusions: NSCLC patients who failed EGFR-TKIs treatment can tolerate adverse reactions related to immunotherapy combined with chemotherapy and bevacizumab treatment. PFS is significantly prolonged in those aged≤65 years and those with moderate and high expression of PD-L1.

Differentiating between normal and fetal growth restriction-complicated placentas: is T2∗ imaging imaging more accurate than conventional diffusion-weighted imaging?

AIM: To compare the performance of T2∗ imaging and apparent diffusion coefficient (ADC) in differentiating normal placentas from those complicated by fetal growth restriction (FGR). MATERIALS AND METHODS: This prospective study included 28 control and 30 FGR placentas. Gradient-echo magnetic resonance imaging (MRI) at 16 different echo times and diffusion-weighted imaging (b-value of 0 and 800 s/mm2) were performed on all pregnant women using a 3 T MRI system. RESULTS: Both T2∗ imaging Z-score and ADC were significantly lower in the FGR placentas (ADC, (1.69 ± 0.19) × 10-3 versus (1.42 ± 0.28) × 10-3 mm2/s, p<0.001; T2∗ imaging Z-score, -0.004 ± 0.95 versus -2.441 ± 1.48, p<0.001). The area under the curve for T2∗ imaging Z-score and ADC was 0.917 (95% confidence interval [CI] = 0.842-0.991) and 0.788 (95% CI = 0.655-0.887), respectively. The performance of T2∗ imaging in differentiating FGR placentas was significantly better than that of ADC (Z = 2.043, p=0.041). CONCLUSION: Placental T2∗ imaging was found to be more reliable than ADC in differentiating between normal and FGR placentas.

Deficient chaperone-mediated autophagy in macrophage aggravates inflammation of nonalcoholic steatohepatitis by targeting Nup85.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.

Body mass index and the risk of abdominal hernia: a Mendelian randomization study.

PURPOSE: Abdominal hernia (AH) is one of the most common clinical diseases. A large number of observational studies have found that obesity is an important risk factor for AH. However, the causal relationship between obesity and AH cannot be determined because of the clinical studies on AH induced by obesity are relatively few and only have some small- or medium-scale observational studies. Observational studies have so many confounding factors and reverse causality due to their shortcomings. From an evidence-based medicine perspective, they are not sufficiently convincing. Therefore, there is still a lack of high-quality, evidence-based medical evidence supporting a causal relationship between obesity and AH. A causal relationship between obesity and AH is also almost impossible to confirm by randomized controlled trials (RCTs). Our study based on Mendelian randomization (MR) may provide a higher level of evidence-based medical support for the relationship between obesity and AH. Body mass index (BMI) is the most common measure used for defining obesity. Finally, we employed two-sample Mendelian randomization (TSMR) to explore the causal relationship between BMI and AH. METHODS: AH-related single nucleotide polymorphisms (SNPs) data were obtained from the FinnGen Biobank (FB), and BMI-related single nucleotide polymorphisms (SNPs) data were obtained from the UK Biobank (UKB). Genetic loci are used as instrumental variables (IVs), methods such as inverse variance weighted (IVW) were used for two-sample Mendelian randomization analysis, and the odds ratio (OR) value was used to evaluate the causal relationship between BMI and AH. RESULTS: The results of the horizontal pleiotropy test were calculated by Egger-intercept method: p = 0.34 > 0.05. The Cochran Q test of MR-Egger method and IVW method showed heterogeneity P = 0.03 < 0.05, so the IVW random effect model was used as the gold standard. We found a genetically determined 1-standard deviation (SD) increment of BMI causally increased a 66.0% risk of AH (N = 371 SNPs, OR = 1.66, 95% CI 1.46-1.89, p = 1.55E-14) based on the IVW random effect model which was almost consistent with the results of other seven methods. CONCLUSIONS: Our MR found genetic evidence for BMI and AH. The risk of developing AH increases with the number of BMI. This finding provides further evidence that maintaining a healthy BMI can prevent the development of AH. In addition, clinicians may need to focus on the potential risk of AH on some high-BMI patients.

[Evaluating the efficiency of endoscope-assisted septo-rhinoplasty via intranasal approach].

Objective: To observe the functional and esthetic results of endoscope-assisted septo-rhinoplasty via intranasal approach. Methods: The clinical data of 12 patients with septal deviation and nasal deformity in the University of Hong Kong-Shenzhen Hospital from June 2021 to June 2022 were analyzed, including 8 males and 4 females, aging 28 to 58 years. All patients were operated under general anesthesia. The septal deviation was corrected by hemitransfixion incision, combined with intercartilaginous incision and other intranasal or extranasal incisions to perform osteotomy, hump resection and saddle nose correction. Patient satisfaction with postoperative functional and aesthetic improvements was assessed through Nasal Obstruction Symptom Evaluation (NOSE), Rhinoplasty Outcome Evaluation (ROE), and Visual Analogue Scale (VAS).SPSS 25 software was used for statistical analysis. Results: The correction of nasal septum deviation was satisfactory in all 12 patients. Nasal obstruction was relieved, with NOSE score and VAS score of nasal ventilation decreased [(21.67±10.30) vs (70.83±14.12), (1.83±1.03) vs (8.33±0.89), t value was 9.49 and 16.30, respectively, both P<0.05]. The nasal appearance of 10 patients with crooked nose deformity was improved, with ROE score and VAS score of nasal appearance increased [(21.30±2.31) vs (8.10±3.31), (8.90±0.99) vs (3.80±1.62), t value was -11.85 and -9.33, respectively, both P<0.05];The nasal vestibule morphology of 2 patients with abnormal nasal vestibule was improved. During the follow-up of 12 to 24 months, no postoperative complication such as nasal septum perforation, nasal cavity adhesion or nasal dorsal collapse occurred in all patients. Conclusion: Endoscope-assisted septo-rhinoplasty via intranasal approach can resolve both functional and esthetic problems at the same time, improving outcomes while reducing surgical trauma.

[Relationship of serum uric acid with prediabetes and newly detected type 2 diabetes mellitus].

Objective: To evaluate the relationship of serum uric acid with prediabetes and newly detected type 2 diabetes mellitus (T2DM) in adults. Methods: Data were obtained from the baseline investigation of Songjiang Peak-Plan cohort. According to the baseline fasting plasma glucose and glycosylated hemoglobin, the eligible subjects were divided into normal blood sugar group, prediabetes group, and newly detected T2DM group. Unconditional logistic regression model was used to explore the effect of serum uric acid level on prediabetes and newly detected T2DM, and restricted cubic spline (RCS) function was used to explore the nonlinear dose-response relationship of serum uric acid level with the prevalence of prediabetes and newly detected T2DM. Results: A total of 30 375 subjects were included in the analysis, with an average age of (55.36±11.52) years, and 60.2% (18 299) of them were women. The baseline survey found that the prevalence of prediabetes was 38.6% (11 739 cases), and the prevalence of newly detected T2DM was 6.6% (1 992 cases). Logistic regression analysis showed that, in women, for every 10µmol/L increase in serum uric acid, the risk of developing prediabetes and T2DM s increased by 2.4% (OR=1.024, 95%CI: 1.018-1.030), and 1.5% (OR=1.015, 95%CI: 1.005-1.025), respectively; in men, for every 10 µmol/L increase in serum uric acid, the risk of developing prediabetes and T2DM decreased by 0.8% (OR=0.992, 95%CI: 0.987-0.998) and 5.0% (OR=0.950, 95%CI: 0.939-0.960), respectively. The RCS function showed that the serum uric acid level showed a nonlinear dose-response relationship with newly detected T2DM (P=0.017), but not with prediabetes (P=0.670) in women and showed a nonlinear dose-response relationship with both prediabetes (P=0.040) and newly detected T2DM (P<0.001) in men. Conclusions: Adult women are at increased risk of prediabetes and newly detected T2DM with increase of serum uric acid level, and adult men are at decreased risk of newly diagnosed T2DM with the increase of serum uric acid level. There was no significant relationship between serum uric acid level and prediabetes in men.

[The effect of human chorionic gonadotropin day serum progesterone level on the live birth rate of fresh embryo transfer with GnRH antagonist protocols].

Objective: To investigate the effect of human chorionic gonadotropin (HCG)day serum progesterone (P) level on the live birth rate (LBR) of fresh embryo transfer with GnRH antagonist protocols. Methods: Patients who underwent the first IVF/ICSI in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were included for analysis. The patients with normal ovarian response with GnRH antagonist protocols were included (n=765). The receiver operating characteristic curve (ROC) was used to select the optimal cut-off value of serum P on HCG day (0.83 µg/L), and the included cycles were divided into two groups: P<0.83 µg/L (n=444) and P≥0.83 µg/L (n=321). The primary outcome measure was LBR. Secondary outcome measures included clinical pregnancy rate (CPR) and early miscarriage rate. The difference of the above indexes between the two groups was compared. Multivariate logistic regression model was used to analyze the effect of serum P level on LBR in fresh embryo transfer cycles. Results: The maternal ages in P<0.83 µg/L group and P≥0.83 µg/L group were (32.40±5.49) years and (32.53±5.51) yeas, respectively. The paternal ages were (33.35±6.34) years and (33.43±6.38) years, respectively of which, the difference was not statistically significant (P>0.05). The CPR in the P<0.83 µg/L group was 45.9% (n=204), which was significantly higher than that in the P≥0.83 µg/L group (37.1%) (n=119) (P=0.014). There was no significant difference in the early miscarriage rate between the two groups [14.2% (n=29) vs 14.3% (n=17), P=0.986]. The LBR in the P<0.83 µg/L group was significantly higher than that in the P≥0.83 µg/L group [36.3% (n=161) vs 28.0% (n=90), P=0.017]. By multivariate logistic regression model analysis, the maternal age, type of embryo transferred, number of embryos transferred, endometrial thickness on HCG day and serum P level on HCG day were independent risk factors of LBR. The adjust OR(95%CI) were 0.91(0.88-0.94), 2.36(1.04-5.35), 1.84(1.14-2.95), 1.16(1.07-1.25)and 0.63(0.44-0.89), all P<0.05. Conclusion: When the GnRH antagonist protocol is applied in the normal ovarian response population, as the serum P on the HCG trigger day≥0.83 µg/L, the CPR and LBR of fresh embryo transfer are decreased.

Anti-obesity effect of escin: a study on high-fat diet-induced obese mice.

OBJECTIVE: Obesity is characterized by excess fat accumulation and closely associated with insulin resistance and type 2 diabetes. We aimed at exploring the potential effect and mechanism of escin for the treatment of obesity using network pharmacology, and to verify the effect of escin on obese mice. MATERIALS AND METHODS: Escin targets were predicted by DrugBank and SwissTarget database. Potential targets for the treatment of obesity were identified based on the DisGeNET database. Comparative analysis was used to investigate the overlapping genes between escin targets and obesity treatment-related targets. Using STRING database and Cytoscape to analyze interactions among overlapping genes, hub genes were identified. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted in DAVID. High-fat diet (HFD) -induced obese mice were used to observe the anti-obesity effects of escin. The body weight, relevant biochemical markers and HE staining of fat and liver tissues were determined after escin was administered for 18 weeks. RESULTS: We screened 53 overlapping genes for escin and obesity. The mechanism of intervention of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4). The screening and enrichment analysis revealed that the treatment of obesity using escin primarily involved 10 GO enriched terms and 13 related pathways. In vivo, escin can reduce the body weight of obese mice induced by HFD and improve lipid metabolism through lowering triglycerides (TG), total cholesterol (TC), and density lipoprotein (LDL) levels and increasing high density lipoprotein (HDL) levels and decreasing leptin level and increasing adiponectin (ADPN) level. Escin can regulate glucose metabolism caused by obesity through decreasing fasting glucose, postprandial blood glucose and regulating the level of insulin. These obese mice induced by HFD displayed the increased insulin resistance that was associated with the increased inflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Escin may antagonize the increase of MCP-1 and partially antagonize the low-grade inflammation caused by obesity. From the morphological changes of fat and liver tissues stained by HE stain, escin could decrease the size of adipocytes and improve liver necrosis and fatty degeneration in obese mice fed by HFD. CONCLUSIONS: The network pharmacology of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4), 10 GO enriched terms and 13 related pathways. In vivo, escin can be potentially used to prevent or treat obesity through reducing the weight, improving glucose and lipid metabolism, partially antagonizing the low-grade inflammation, and improved insulin resistance.