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Remimazolam is a new benzodiazepine. Currently, it remains unclear how repeated exposure to remimazolam affects the cognitive function of the developing brain. In the present study, the equivalent doses of the two sedatives were derived from S-shaped dose-response curves, and the ED95 of remimazolam was 45 mg/kg (95% CI 37.579-79.280), and for midazolam, it was 77 mg/kg (95% CI 63.751-127.21) using probability analysis. Then, we evaluated the effects of remimazolam and midazolam on cognitive function in juvenile mice (C57BL/6) through Y-maze and MWM. TUNEL staining was used to observe the apoptosis of neurons in hippocampus, western blotting was used to detect the expression changes of related proteins, and the changes of LTP were observed by recording the activity of neurons through electrical stimulation. We found that there was no significant difference in the behavior of mice in MWM. However, the short-term memory of developing mice was impaired in Y-maze after repeated exposure to remimazolam and midazolam. Furthermore, our data demonstrated that the short-term memory damage caused by remimazolam is lighter than midazolam. Concurrently, the extent of caspase-3 upregulation, the number of neuronal apoptosis in CA1 and CA3 regions, a downward trend of PSD95 and BDNF in the hippocampus, and the inhibition of LTP were highly consistent with the behavior of short-term memory impairment. These results indicate that the degree of memory impairment caused by remimazolam is milder than that caused by midazolam, making it a potential replacement for midazolam in repeated medication and long-term sedation in children., Competing Interests: Declarations Ethical approval and consent to participate Our study was approved by the Zunyi medical university. Consent for publication Our manuscripts do not contain personal data in any case. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: There is a general rise in incidentally found pulmonary nodules (PNs) requiring follow-up due to increased CT use. Biopsy and repeated CT scan are the most useful methods for distinguishing between benign PNs and lung cancer, while they are either invasive or involves radiation exposure. Therefore, there has been increasing interest in the analysis of exhaled volatile organic compounds (VOCs) to distinguish between benign PNs and lung cancer because it's cheap, noninvasive, efficient, and easy-to-use. However, the exact value of breath analysis in this regard remains unclear., Methods: A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-oriented systematic search was performed to include studies that established exhaled VOC-based predictive models to distinguish between benign PNs and lung cancer and reported the exact VOCs used. Data regarding study characteristics, performance of the models, which predictors were incorporated, and methodologies for breath collection and analysis were independently extracted by two researchers. The exhaled VOCs incorporated into the predictive models were narratively synthesized, and those compounds that were reported in > 2 studies and reportedly exhibited consistent associations with lung cancer were considered key breath biomarkers. A quality assessment was independently performed by two researchers using both the Newcastle-Ottawa Scale (NOS) and the Prediction Model Risk of Bias Assessment Tool (PROBAST)., Results: A total of 11 articles reporting on 46 VOC-based predictive models were included. The majority relied solely on exhaled VOCs (n = 44), while two incorporated VOCs, demographical factors, and radiological signs. The variation in the sensitivity, specificity, and AUC indicators of the models that incorporated multiple factors was lower compared with those of the models that relied solely on exhaled VOCs. A total of 84 VOCs were incorporated. Of these, 2-butanone, 3-hydroxy-2-butanone, and 2-hydroxyacetaldehyde were identified as key predictors that had significantly higher concentrations in the exhaled breath samples of patients with lung cancer. Substantial heterogeneity was observed in terms of the modeling and validation methods used, as well as the approaches to breath collection and analysis. Many of the reports were missing certain key pieces of clinical and methodological information., Conclusions: Although exhaled VOC-based models for predicting cancer risk might be a conceivable role as monitoring tools for PNs risk, there has been little overall change in the accuracy of these tests over time, and their role in routine clinical practice has not yet been established., Clinical Trial Number: PROSPERO registration number CRD42023381458., (© 2024. The Author(s).)

Background: The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients., Methods: In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA., Results: A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20-3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84-1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar., Conclusion: OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population., Trial Registration: Clinicaltrials.gov; No: NCT03362385., (© 2024. The Author(s).)

Background: Several health institutions developed strategies to improve health content on Wikimedia platforms given their unparalleled reach. The objective of this study was to compare an online volunteer-based Wikimedia outreach campaign with university course Wikipedia assignments (both focused on improving hearing health content in Wikimedia's public digital knowledge archives), in terms of the reach of the contributions and the extent of the participants' input. A secondary objective was to examine the feasibility and the implementation of the different strategies., Methods: The research team partnered for the (1) coordination of improvements in hearing and healthcare content through educational programs using Wikimedia platforms, (2) participation in the global campaign Wiki4WorldHearingDay2023 and (3) evaluation of the proposed strategies. Metrics used in the comparison of the two strategies included the number of articles edited, number of views of the edited articles (as reach) and the extent of edits, captured as the number of words. The feasibility evaluation included assessing recruitment success and the implementation of the proposed plan among faculty, students from various university programs, and volunteers representing different constituencies., Results: The effort increased the availability of quality plain language information on hearing conditions and hearing care. Both strategies demonstrated to be feasible by their success in recruiting participants who contributed to the effort and by measurable outputs as edits. The contribution of content to Wikimedia platforms as part of education activities provided a more robust result. Wiki4WorldHearingDay2023 145 participants (78 from educational programs) contributed 167,000 words, 258 + references and 140 images to 322 Wikipedia articles (283 existing and 39 new ones), which were viewed 16.5 million times. Contributions occurred in six languages. Edits in Portuguese, mainly by those involved in educational programs, led the number of articles (226 or 70.2%) that were expanded or created during the 5-month tracking period., Conclusions: The elements that contributed to the success of the studied strategies include an impact topic, coordination with educational programs, international multidisciplinary collaborations, the dissemination of the initiative in several platforms, connection with a robust local Wikimedia affiliate, and the use of a technical infrastructure that provides metrics and coordination mechanisms., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Cardiometabolic multimorbidity (CMM) is a growing global health problem, and obstructive sleep apnea (OSA) is recognized as an important risk factor for cardiovascular disease. However, the impact of OSA on the prognosis of CMM patients remains unclear., Methods: This study was a sub-study of OSA-acute coronary syndrome (ACS) and included 1, 927 hospitalized ACS patients. Patients were divided into the CMM group and the non-CMM group. OSA was diagnosed using the apnea-hypopnea index (AHI). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoint included cardiac events, all-cause death and all repeat revascularizations., Results: This study enrolled 1, 927 patients hospitalized for ACS, with a median follow-up of 3 years. Among them, 723 patients (37.5%) had CMM, while 1, 204 patients (62.5%) did not have CMM. Over half of the patients in each group had OSA. OSA patients exhibited worse cardiometabolic profiles than their non-OSA counterparts, including higher body mass index (BMI), glycemic indices, lipids and inflammation. In the CMM group, OSA patients had a significantly higher incidence of MACCE than non-OSA patients (34.7% vs. 23.7%, p = 0.004). These results remained significant after adjustment, indicating that OSA substantially increased the risk of MACCE in the CMM group (adjusted hazard ratio [HR]: 1.432; 95% confidence interval [CI]: 1.017-2.016; p = 0.040). Conversely, the incidence of MACCE was similar between OSA and non-OSA subgroups within the non-CMM cohort. Subgroup analyses showed that OSA increased the risk of MACCE in CMM patients aged ≥ 60 years (adjusted HR: 1.642; 95% CI: 1.031-2.615; p = 0.037) and in those with specific clinical characteristics., Conclusion: OSA significantly impacts the prognosis of CMM patients, highlighting the need for targeted OSA screening and management strategies to improve outcomes in this population potentially., (© 2024. The Author(s).)

Background: Alkaloids, important secondary metabolites produced by plants, play a crucial role in responding to environmental stress. Heuchera micrantha, a well-known plant used in landscaping, has the ability to purify air, and absorb toxic and radioactive substances, showing strong environmental adaptability. However, there is still limited understanding of the accumulation characteristics and metabolic mechanism of alkaloids in H. micrantha., Results: In this study, four distinct varieties of H. micrantha were used to investigate the accumulation and metabolic traits of alkaloids in its leaves. We conducted a combined analysis of the plant's metabolome and transcriptome. Our analysis identified 44 alkaloids metabolites in the leaves of the four H. micrantha varieties, with 26 showing different levels of accumulation among the groups. The HT and JQ varieties exhibited higher accumulation of differential alkaloid metabolites compared to YH and HY. We annotated the differential alkaloid metabolites to 22 metabolic pathways, including several alkaloid metabolism. Transcriptome data revealed 5064 differentially expressed genes involved in these metabolic pathways. Multivariate analysis showed that four key metabolites (N-hydroxytryptamine, L-tyramine, tryptamine, and 2-phenylethylamine) and three candidate genes (Cluster-15488.116815, Cluster-15488.146268, and Cluster-15488.173297) that merit further investigation., Conclusions: This study provided preliminarily insight into the molecular mechanism of the biosynthesis of alkaloids in H. micrantha. However, further analysis is required to elucidate the specific regulatory mechanisms of the candidate gene involved in the synthesis of key alkaloid metabolites. In summary, our findings provide important information about how alkaloid metabolites build up and the metabolic pathways involved in H. micrantha varieties. This gives us a good starting point for future research on the regulation mechanism, and development, and utilization of alkaloids in H. micrantha., (© 2024. The Author(s).)

Background: The aim of the study was to investigate the relationship between sedentary behavior, screen time and MetS among Chinese children and adolescents aged 7-17 years. Data was obtained from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017., Methods: Data on sedentary time, screen time, and MetS indicators were obtained through physical and health questionnaires, anthropometric measurements, and clinical examinations. MetS was defined according to the Cook's criteria. Wilcoxon rank sum test and chi-square test were applied for comparisons of measurement data and counting data, respectively. The relationship between sedentary time, screen time, and MetS and its components was analyzed using a multivariate logistic regression model., Results: The prevalence of MetS among 7-17-year-old students in 2016-2017 was 5.45%. Compared to those with low sedentary behavior, in high sedentary behavior groups, the prevalence of abdominal obesity, high TG, low HDL-C, and MetS was high in boys, and the prevalence of abdominal obesity, high TG, hyperglycemia, and MetS was high in girls. Moreover, for those who reported ≥ 3 h/day of screen time, the prevalence of abdominal obesity, low HDL-C, and MetS was higher in boys, and the prevalence of abdominal obesity and MetS was higher in girls. After adjusting for confounding variables, the risks of abdominal obesity, high TG, low HDL-C, and MetS were higher in high-level sedentary time group, and the risks of abdominal obesity and MetS were 1.15 and 1.14 times higher for those who spent ≥ 3 h/day on screen time, respectively., Conclusions: This study shows that high levels of sedentary time and screen time were associated with an increased likelihood of MetS among Chinese children and adolescents aged 7-17 years. Reducing sedentary behavior and screen time may contribute to the prevention of metabolic diseases., (© 2024. The Author(s).)

Background: Mental health is a matter of quality of life among older adults. This study aimed to explore the association between the socioeconomic status (SES) perception and mental health of older adults using data from 2017 Chinese General Social Survey (CGSS)., Methods: Ordinary least squares (OLS) regression was used to analyse the association between SES perception and mental health, and the substitution model and variable methods were used to check the robustness of the results. Moreover, we adopted the Sobel model to analyse the mediating roles of social trust and justice., Results: SES perception was positively associated with mental health, and this association was mediated by social trust and justice. This kind of positive association was mainly embodied in those groups with the highest or lowest objective SES. In other words, this study confirmed the phenomenon of "a contented mind is a perpetual feast" in Chinese society., Conclusions: Higher SES perception is associated with improved mental health for Chinese older adults. It is imperative to prioritize efforts to enhance the perceptual abilities of older adults, particularly those with the highest or lowest objective SES, to promote their overall subjective well-being., (© 2024. The Author(s).)

Background: The presence of infarction in patients with unrecognized myocardial infarction (UMI) is a critical feature in predicting adverse cardiac events. This study aimed to compare the detection rate of UMI using conventional and deep learning reconstruction (DLR)-based late gadolinium enhancement (LGE O and LGE DL , respectively) and evaluate optimal quantification parameters to enhance diagnosis and management of suspected patients with UMI., Methods: This prospective study included 98 patients (68 men; mean age: 55.8 ± 8.1 years) with suspected UMI treated at our hospital from April 2022 to August 2023. LGE O and LGE DL images were obtained using conventional and commercially available inline DLR algorithms. The myocardial signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and percentage of enhanced area (P area ) employing the signal threshold versus reference mean (STRM) approach, which correlates the signal intensity (SI) within areas of interest with the average SI of normal regions, were analyzed. Analysis was performed using the standard deviation (SD) threshold approach (2SD-5SD) and full width at half maximum (FWHM) method. The diagnostic efficacies based on LGE DL and LGE O images were calculated., Results: The SNR DL and CNR DL were two times better than the SNR O and CNR O , respectively (P < 0.05). P area-DL was elevated compared to P area-O using the threshold methods (P < 0.05); however, no intergroup difference was found based on the FWHM method (P > 0.05). The P area-DL and P area-O also differed except between the 2SD and 3SD and the 4SD/5SD and FWHM methods (P < 0.05). The receiver operating characteristic curve analysis revealed that each SD method exhibited good diagnostic efficacy for detecting UMI, with the P area-DL having the best diagnostic efficacy based on the 5SD method (P < 0.05). Overall, the LGE DL images had better image quality. Strong diagnostic efficacy for UMI identification was achieved when the STRM was ≥ 4SD and ≥ 3SD for the LGE DL and LGE O , respectively., Conclusions: STRM selection for LGE DL magnetic resonance images helps improve clinical decision-making in patients with UMI. This study underscored the importance of STRM selection for analyzing LGE DL images to enhance diagnostic accuracy and clinical decision-making for patients with UMI, further providing better cardiovascular care., (© 2024. The Author(s).)

Background: The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients., Methods: Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality., Results: Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P < 0.001), lower rates of intraoperative transfusion (10.4% vs. 19.0%, P = 0.029), more lymph node harvest (11.0 vs. 10.0, P = 0.014) and shorter postoperative length of stay (LOS) (13.0 vs. 16.0 days, P = 0.013). There were no significant differences in serious complications, reoperation, 90-day readmission and mortality rates (all P > 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM., Conclusions: It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD., (© 2024. The Author(s).)

Background: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC., Methods: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy., Results: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients., Conclusions: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC., Trial Registration: ClinicalTrials.gov (NCT04401800)., (© 2024. The Author(s).)

Purpose: This study aimed to investigate the risk factors for liver disease comorbidity among older adults in eastern, central, and western China, and explored binary, ternary and quaternary co-morbid co-causal patterns of liver disease within a health ecological model., Method: Basic information from 9,763 older adults was analyzed using data from the China Health and Retirement Longitudinal Study (CHARLS). LASSO regression was employed to identify significant predictors in eastern, central, and western China. Patterns of liver disease comorbidity were studied using association rules, and spatial distribution was analyzed using a geographic information system. Furthermore, binary, ternary, and quaternary network diagrams were constructed to illustrate the relationships between liver disease comorbidity and co-causes., Results: Among the 9,763 elderly adults studied, 536 were found to have liver disease comorbidity, with binary or ternary comorbidity being the most prevalent. Provinces with a high prevalence of liver disease comorbidity were primarily concentrated in Inner Mongolia, Sichuan, and Henan. The most common comorbidity patterns identified were "liver-heart-metabolic", "liver-kidney", "liver-lung", and "liver-stomach-arthritic". In the eastern region, important combination patterns included "liver disease-metabolic disease", "liver disease-stomach disease", and "liver disease-arthritis", with the main influencing factors being sleep duration of less than 6 h, frequent drinking, female, and daily activity capability. In the central region, common combination patterns included "liver disease-heart disease", "liver disease-metabolic disease", and "liver disease-kidney disease", with the main influencing factors being an education level of primary school or below, marriage, having medical insurance, exercise, and no disabilities. In the western region, the main comorbidity patterns were "liver disease-chronic lung disease", "liver disease-stomach disease", "liver disease-heart disease", and "liver disease-arthritis", with the main influencing factors being general or poor health satisfaction, general or poor health condition, severe pain, and no disabilities., Conclusion: The comorbidities associated with liver disease exhibit specific clustering patterns at both the overall and local levels. By analyzing the comorbidity patterns of liver diseases in different regions and establishing co-morbid co-causal patterns, this study offers a new perspective and scientific basis for the prevention and treatment of liver diseases., (© 2024. The Author(s).)

Background: Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer., Methods: This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations., Results: The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism., Conclusion: This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients., (© 2024. The Author(s).)

Background: To investigate the prevalence and risk factors for astigmatism in 7-19-year-old students in Xinjiang, China., Methods: A school-based, cross-sectional study was conducted on students who underwent refraction examination in Xinjiang, China, between May and December 2019. The prevalence of astigmatism was determined. Astigmatism was defined as cylinder power (C) ≤-0.75 D, undefined astigmatism as ≤-1.50 D, and high astigmatism as C ≤-3.00 D. Astigmatism types were: against-the-rule astigmatism (maximum refraction of the main meridian in 180° ± 30°), with-the-rule astigmatism (maximum refraction of the main meridian at 90°±30°), and oblique astigmatism (all other cases)., Results: Of the 71,838 students examined (51.0% boys, 7 - 19 years old), 25,945 (36.1%, 95%CI: 35.52-36.68%) had astigmatism and 1267 (1.8%, 95%CI: 1.07-2.53%) had high astigmatism. The prevalence of astigmatism was greater in Han individuals (39.6%) compared with the Hui (34.0%), Kazakh (34.0%), Kyrgyz (32.1%), and Uyghur (26.4%) populations. Among the 25,945 students with astigmatism, 19,947 had with-the-rule astigmatism (76.9%), 3405 had against-the-rule astigmatism (13.1%), and 2593 had oblique astigmatism (10.0%). Multivariable logistic regression analysis showed that ethnicity (Han individuals more susceptible), male gender, age, and refractive errors (myopia and hyperopia) were independently associated with astigmatism, high astigmatism, and with-the-rule astigmatism (all P < 0.05)., Conclusions: The prevalence of astigmatism among children and adolescents in Xinjiang was 36.1%, including 1.8% of high astigmatism. In this population, astigmatism was mainly of the with-the-rule astigmatism type (76.9%). Han ethnicity, male gender, and myopia or hyperopia were independently associated with a high risk of astigmatism., (© 2024. The Author(s).)

Background: Occupational hazards occur in all walks of life. China's horticulture industry is undergoing rapid development. However, the mental health of garden workers has not received much attention. This study investigates the mental health status and influencing factors of Chinese garden workers and provides a basis for promoting their mental health and ensuring the healthy development of Chinese horticulture., Methods: A cross-sectional survey of garden workers in Beijing was conducted from 10 July 2021 to 10 October 2021. A total of 3349 valid questionnaires were recovered, with an effective response rate of 95.69%. Descriptive statistical analysis was carried out on the demographic characteristics, job satisfaction, stress, anxiety, and depression of garden workers, and the influencing factors affecting the mental health of Chinese garden workers were found through a t-test, variance analysis, and ordinal multi-class logistic regression analysis., Results: Survey respondents were mostly male (54.4%) and under the age of 40 (64.1%). The anxiety and depression symptoms of the garden workers were moderate. Among staff members, 40.2% were in a normal state of stress. Gender, three meals on time, monthly income, and job satisfaction were the factors influencing stress, anxiety, and depression symptoms among garden workers., Conclusion: Compared to medical staff and other groups, the stress, anxiety, and depression symptoms of Chinese garden workers are severe. Gender, monthly income, and job satisfaction are important factors affecting their mental health. Managers should continuously improve the working environment of garden workers, provide salaries that match their positions, and improve their job recognition and satisfaction to reduce the impact of negative emotions on personal health., (© 2024. The Author(s).)

Background: The objective of the current study was to investigate the correlation between trajectories of maternal perinatal depression (PND) spanning from early pregnancy to one year postpartum and developmental delays observed in one-year-old children., Methods: The dataset under examination encompassed 880 women who took part in a mother-child birth study conducted in China. Latent class growth analysis (LCGA) was employed to identify patterns in Edinburgh Postnatal Depression Scale (EPDS) scores of women, spanning from early pregnancy to one year postpartum. To assess the neurodevelopment of one-year-old children, a Chinese version of the Bayley Scale of Infant Development (BSID-CR) was employed. Logistic regression was employed to explore the association between PND trajectories and developmental delays in children, with appropriate covariate adjustments., Results: The trajectories of maternal PND identified in this study included a minimal-stable symptom group (n = 155), low-stable symptom group (n = 411), mild-stable symptom group (n = 251), and moderate-stable symptom group (n = 63). Logistic regression analysis revealed that mothers falling into the moderate-stable symptom group exhibited a notably heightened risk of having a child with psychomotor developmental delays at the age of one year., Conclusions: The findings drawn from a representative sample in China provide compelling empirical evidence that bolsters the association between maternal PND and the probability of psychomotor developmental delays in children. It is imperative to develop tailored intervention strategies and meticulously design mother-infant interactive intervention programs for women with PND., (© 2024. The Author(s).)

The breakthrough high-throughput measurement of the cis-regulatory activity of millions of randomly generated promoters provides an unprecedented opportunity to systematically decode the cis-regulatory logic that determines the expression values. We developed an end-to-end transformer encoder architecture named Proformer to predict the expression values from DNA sequences. Proformer used a Macaron-like Transformer encoder architecture, where two half-step feed forward (FFN) layers were placed at the beginning and the end of each encoder block, and a separable 1D convolution layer was inserted after the first FFN layer and in front of the multi-head attention layer. The sliding k-mers from one-hot encoded sequences were mapped onto a continuous embedding, combined with the learned positional embedding and strand embedding (forward strand vs. reverse complemented strand) as the sequence input. Moreover, Proformer introduced multiple expression heads with mask filling to prevent the transformer models from collapsing when training on relatively small amount of data. We empirically determined that this design had significantly better performance than the conventional design such as using the global pooling layer as the output layer for the regression task. These analyses support the notion that Proformer provides a novel method of learning and enhances our understanding of how cis-regulatory sequences determine the expression values., (© 2024. The Author(s).)

Backgrounds: The internal fixation for rib fracture with single-operation-port (two ports) complete video-assisted thoracoscopic surgery (VATS) is a promising surgical approach for treating multiple rib fractures. The study aimed to investigate the minimally invasive surgical procedure's clinical effect in treating multiple rib fractures., Methods: Seventy-three patients with multiple rib fractures were divided into two groups according to surgical procedure. In the study group, 42 patients were operated on with the internal fixation of rib fracture with single-operation-port complete VATS. In the control group, this study performed the open operative internal fixation for rib fracture with traditional thoracotomy on 31 patients. The surgical-related indexes were retrospectively analyzed. These included the operative time, the intraoperative blood loss, the drainage amount of the chest tube, the placement time of the chest tube, the postoperative hospital stay, the incidence of postoperative complications, the imaging efficacy of rib fixation of rib fractures, and visual analog scale of pain scoring (VAS scoring)., Results: There was no difference in the operative time between the study and control groups (P = 0.806). The intraoperative blood loss, the chest tube drainage amount, the chest tube placement time, the postoperative hospital stay, and the incidence of postoperative complications in the study group were lower than those in the control group (P < 0.05). There was no significant difference in the imaging efficacy of rib fixation of rib fractures between the two groups (P = 0.806). VAS scores in the study group on the seventh postoperative day were significantly reduced compared with the control group (P = 0.026)., Conclusion: The internal fixation for rib fractures with single-operation-port complete VATS is a feasible, safe, simple, and minimally invasive surgical procedure to treat multiple rib fractures, which is worthy of clinical application., (© 2024. The Author(s).)

Background: Gastric cancer (GC) constitutes a major global health problem, of which remnant gastric cancer (RGC) occurs less frequently. The rate of RGCs after gastrectomy for GC is increasing recently due to improved survival and screening, however, their incidence and risk have not been reported in the U.S., Population: The objective of this study was to evaluate the incidence and elevated risk of RGC after GC gastrectomy in this population, and to identify the risk factors., Methods: Patients underwent gastrectomy for first primary GC in 2000-2015 and those who developed RGC were identified from Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray regression was used to estimate the cumulative incidence and to identify risk factors. Standardized incidence ratios (SIRs) were calculated by Poisson regression to compare the risk with the general population., Results: Among 21,566 patients included in the cohort, 227 developed RGC. The 20-year cumulative incidence of RGC was 1.88%. Multivariate analysis revealed that older age, invasion depth, male sex, marital status, and lower income are independent risk factors for RGC development. SIR was 7.70 overall and > 4.5 in each stratum., Conclusions: Cumulative incidence and risk for RGCs increased continuously in patients underwent GC gastrectomy. Close and lifelong endoscopy surveillance should be recommended for patients who received GC gastrectomy, especially those with high-risk factors., (© 2024. The Author(s).)

Purposes: Low HDL-C is associated with an increased risk of sepsis-associated AKI and subsequent decline in eGFR. HDL-C possesses anti-inflammatory, antioxidant, and endothelial repair-promoting properties. The use of Apo A-I mimetic peptides, which are the main structural components of HDL-C, has been shown to improve renal function in animal models of sepsis. However, the diagnostic value of low HDL-C in persistent sepsis-associated AKI remains unclear., Methods: This is a retrospective cohort study based on MIMIC IV (V 2.2). The study population consisted of all adult septic patients admitted to the Beth Israel Deaconess Medical Center Intensive Care Unit from 2008 to 2019, with plasma HDL-C measured within 24 h of ICU admission. The primary endpoint was persistent severe sepsis-associated acute kidney injury (SA-AKI) and the secondary endpoint is kidney replacement therapy (KRT). Logistic regression was used to assess the correlation between HDL-C and persistent severe SA-AKI and KRT, and receiver operating characteristic (ROC) curve analysis was performed to evaluate predictive ability., Results: A total of 604 cases of SA-AKI patients were included in the analysis, among which 88 cases (14.5%) experienced persistent severe SA-AKI. The median (IQR) HDL-C level in the group with persistent severe SA-AKI was lower (33.0 [24.0-45.5]) compared to the non-persistent severe SA-AKI group (42.0 [31.0-53.0]). However, HDL-C showed poor discriminatory ability with an AUROC [95%CI] of 0.62 [0.56-0.69]. Clinical prediction models based on serum creatinine concentration, 24-h creatinine change, APSIIIscore, lactate levels, APTT, and heart rate performed well in predicting persistent severe SA-AKI with an AUROC [95%CI] of 0.876 [0.84-0.91]. However, adding HDL-C to this model did not improve predictive performance., Conclusions: The plasma HDL-C measured within 24 h after admission to the ICU does not provide a good prediction for persistent severe SA-AKI, and it does not improve the clinical predictive ability compared to conventional variables., (© 2023. The Author(s).)

T cell-based adoptive cell therapy (ACT) has exhibited excellent antitumoral efficacy exemplified by the clinical breakthrough of chimeric antigen receptor therapy (CAR-T) in hematologic malignancies. It relies on the pool of functional T cells to retain the developmental potential to serially kill targeted cells. However, failure in the continuous supply and persistence of functional T cells has been recognized as a critical barrier to sustainable responses. Conferring stemness on infused T cells, yielding stem cell-like memory T cells (T SCM ) characterized by constant self-renewal and multilineage differentiation similar to pluripotent stem cells, is indeed necessary and promising for enhancing T cell function and sustaining antitumor immunity. Therefore, it is crucial to identify T SCM cell induction regulators and acquire more T SCM cells as resource cells during production and after infusion to improve antitumoral efficacy. Recently, four common cytokine receptor γ chain (γc) family cytokines, encompassing interleukin-2 (IL-2), IL-7, IL-15, and IL-21, have been widely used in the development of long-lived adoptively transferred T SCM in vitro. However, challenges, including their non-specific toxicities and off-target effects, have led to substantial efforts for the development of engineered versions to unleash their full potential in the induction and maintenance of T cell stemness in ACT. In this review, we summarize the roles of the four γc family cytokines in the orchestration of adoptively transferred T cell stemness, introduce their engineered versions that modulate T SCM cell formation and demonstrate the potential of their various combinations. Video Abstract., (© 2023. The Author(s).)

Background: Studies examining the relationships of stressful life events and cancer yielded inconsistent findings, while relevant evidence in mainland China is scarce. The current study sought to determine whether experience of stressful life events was associated with cancer prevalence in Chinese population., Methods: We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million Chinese adults aged 30 to 79 from 2004 to 2008. Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cancer associated with stressful life events reported at baseline., Results: Among the 461,696 participants included in this analysis, 2,122 (0.46%) had self-reported cancer with the mean (SD) age was 57.12 (9.71) years. Compared to those without any stressful life event, participants who experienced 1 and 2 or more events had significantly higher odds of cancer, with the ORs of 1.80 (95% CI: 1.58-2.05) and 3.05 (2.18-4.28). For categories of work-, family-, and personal-related events, the OR of cancer was 1.48 (1.07-2.05), 2.06 (1.80-2.35), and 1.65 (1.17-2.33), respectively. Regarding the specific stressful life events, loss of income/living on debt, major conflict within family, death/major illness of other close family member, and major injury/traffic accident were significantly associated with increased odds of cancer, with the ORs of 2.64 (1.81-3.86), 1.73 (1.20-2.50), 2.36 (2.05-2.72), and 2.11 (1.43-3.13)., Conclusion: Our findings suggested that experiences of cumulative and specific stressful life events were significantly associated with increased cancer prevalence in Chinese population., (© 2023. The Author(s).)

Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO -/- mice had less M1 macrophages in vivo, and ENHO -/- macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages., (© 2023. The Author(s).)

Background: This study explores and compares the influences of family communication patterns (conversation orientation and conformity orientation) on family discussion and preventive behaviors for older parents and their adult children in the context of the early COVID-19 outbreak., Methods: A total of 248 participants, including 117 parents and 131 adult children, participated in an online survey in February 2020. Participants reported family communication patterns, family discussions related to COVID-19, and their preventive behaviors., Results: Conversation orientation was positively associated with information sharing and scientific discussion for older parents and adult children. Our results revealed the differential influences of conformity orientation on older parents and adult children. Conformity orientation was positively associated with scientific discussion for older parents but was not significantly associated with any form of family discussion reported by adult children. There was a significant interaction effect of conversation orientation and conformity orientation on disputed communication within the family, suggesting that conflicts may arise in COVID-related discussions when parents and adult children value conversation and conformity. Scientific discussion was found to mediate the relationships between family communication patterns and preventive behaviors. The effects of scientific discussions were stronger for older parents than for adult children., Conclusions: Family communication patterns can be associated with preventive behaviors through different forms of family discussion about COVID-19. Conversation orientation is a strong facilitator for positive behavioral effects and scientific discussion is the most benign form of family health discussion. Health communication efforts should enhance the agency role of the family and motivate scientific discussion in health practices., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Colorectal cancer is a malignant tumor that poses a serious threat to human health. The main objective of this study is to investigate the mechanism by which Jatrorrhizine (JAT), a root extract from Stephania Epigaea Lo, exerts its anticancer effects in colorectal cancer., Methods: We initially assessed the inhibitory properties of JAT on SW480 cells using MTT and cell scratch assays. Flow cytometry was employed to detect cell apoptosis. Differentially expressed genes were identified through high-throughput sequencing, and they were subjected to functional enrichment and signaling pathway analysis and PPI network construction. RT-qPCR was used to evaluate gene expression and identify critical differentially expressed genes. Finally, the function and role of differentially expressed genes produced by JAT-treated SW480 cells in colorectal cancer will be further analyzed using the TCGA database., Results: Our study demonstrated that JAT exhibits inhibitory effects on SW480 cells at concentrations of 12.5µM, 25µM, 50µM, and 75µM without inducing cell apoptosis. Through high-throughput sequencing, we identified 244 differentially expressed genes. KEGG and GO analysis of high-throughput sequencing results showed that differentially expressed genes were significantly enriched in MAPK, Wnt, and P53 signaling pathways. Notably, JAT significantly altered the expression of genes associated with ferroptosis. Subsequent RT-qPCR showed that the expression of ferroptosis genes SLC2A3 and ASNS was significantly lower in JAT-treated SW480 cells than in the control group. Analysis by TCGA data also showed that ferroptosis genes SLC2A3 and ASNS were significantly highly expressed in COAD. The prognosis of SLC2A3 was significantly worse in COAD compared to the normal group. SLC2A3 may be a core target of JAT for the treatment of COAD., Conclusions: JAT can inhibit COAD growth by ferroptosis-related genes. And it is a potential natural substance for the treatment of COAD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Type 2 Diabetes mellitus (T2DM) has become a major lifestyle disease endangering human health worldwide. Patients with T2DM face varying degrees of loneliness, which adversely affects their family and the larger society. This study investigates the serial multiple mediating roles of depression and self-perceived burden between family function and loneliness in the T2DM population of China., Methods: In total, 260 T2DM patients were included. They rated themselves based on UCLA Loneliness Scale, Self-Rating Depression Scale, Self-Rating Anxiety Scale, Family Care Index, and Self-Perceived Burden Scale. Pearson and Spearman correlation analyses were conducted to clarify the association among variables. The SPSS macro-PROCESS program was used for a series of multiple mediation analyses., Results: Family function, depression, self-perceived burden, and loneliness were significantly correlated (P < 0.01). Family function not only has a direct negative impact (effect = -2.809; SE = 0.213; 95%CI: LL = -3.228, UL = -2.390) on loneliness, but also has an indirect impact on loneliness through the independent mediating role of depression (effect = -0.862; SE = 0.165; 95%CI: LL = -1.202, UL = -0.567) and self-perceived burden (effect = -0.288; SE = 0.107; 95%CI: LL = -0.525, UL = -0.114) and the chain mediating role of depression and self-perceived burden (effect = -0.202; SE = 0.066; 95%CI: LL = -0.342, UL = -0.088)., Conclusions: Diversified interventions aimed at improving family function of T2DM patients would help in reducing the level of depression and self-perceived burden, and ultimately reducing loneliness., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Thoracic outlet syndrome (TOS) with the lower trunk compression of brachial plexus (BP) is difficult to diagnosis. This study aimed to summarize the features of thoracic outlet syndrome (TOS) with the lower trunk compression of brachial plexus observed on high-frequency ultrasonography (HFUS)., Methods: The ultrasound data of 27 patients who had TOS with the lower trunk compression of brachial plexus were collected and eventually confirmed by surgery. The imaging data were compared, and the pathogenesis of TOS was analyzed on the basis of surgical data., Results: TOS occurred predominantly in females (70.4%). Most cases had unilateral involvement (92.6%), mainly on the right side (66.7%). The HFUS features of TOS can be summarized as follows: (1) Lower trunk compression. HFUS revealed focal thinning that reflected compression at the level of the lower trunk; furthermore, the distal part of the nerve was thickened for edema (Affected side: 0.49 ± 0.12 cm vs. Healthy side: 0.38 ± 0.06, P = 0.009), and the cross-sectional area of brachial plexus cords was markedly greater on the injured side than on the healthy side (0.95 ± 0.08 cm² vs. 0.65 ± 0.11 cm², P = 0.004). (2) Hyperechoic fibromuscular bands behind the compressed nerve (mostly the scalenus minimus muscle). (3) Abnormal bony structures: cervical ribs or elongated transverse processes of the 7th cervical vertebra (C7). Surgical results showed that the etiological factors contributing to TOS were (1) muscle hypertrophy and/or fibrosis (100%) and (2) cervical ribs/elongated C7 transverse processes (20.7%)., Conclusion: TOS with the lower trunk compression of brachial plexus can be diagnosed accurately and reliably by high-frequency ultrasound., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Paclitaxel dose-dense regimen has been controversial in clinical trials in recent years. This systematic review and meta-analysis tried to evaluate the efficacy and safety of paclitaxel dose-dense chemotherapy in primary epithelial ovarian cancer., Methods: An electronic search following PRISMA guidelines was conducted (Prospero registration number: CRD42020187622), and then a systematic review and meta-analysis of included literature were initiated to determine which regimen was better., Results: Four randomized controlled trials were included in the qualitative evaluation, and 3699 ovarian cancer patients were included in the meta-analysis. The meta-analysis revealed that the dose-dense regimen could prolong PFS (HR0.88, 95%CI 0.81-0.96; p = 0.002) and OS (HR0.90, 95%CI 0.81-1.02; p = 0.09), but it also increased the overall toxicity (OR = 1.102, 95%CI 0.864-1.405; p = 0.433), especially toxicity of anemia (OR = 1.924, 95%CI 1.548-2.391; p < 0.001), neutropenia (OR = 2.372, 95%CI 1.674-3.361; p < 0.001). Subgroup analysis indicated that the dose-dense regimen could significantly prolong not only PFS (HR0.76, 95%CI 0.63-0.92; p = 0.005 VS HR0.91, 95%CI 0.83-1.00; p = 0.046) but also OS (HR0.75, 95%CI 0.557-0.98; p = 0.037 VS HR0.94, 95%CI 0.83-1.07; p = 0.371) in Asian, and overall toxicity was significantly increased in Asians (OR = 1.28, 95%CI: 0.877-1.858, p = 0.202) compared to non-Asians (OR = 1.02, 95%CI 0.737-1.396, p = 0.929)., Conclusion: Paclitaxel dose-dense regimen could prolong PFS and OS, but it also increased the overall toxicity. Therapeutic benefits and toxicity of dose-dense are more obvious in Asians compared to non-Asians, which need to be further confirmed in clinical trials., (© 2023. The Author(s).)

Background: Twenty-three percent of patients are diagnosed with diabetes mellitus after the first episode of acute pancreatitis. The incidence of post-acute pancreatitis diabetes mellitus is significantly higher than that of type 1 diabetes mellitus. Some studies have concluded that the all-cause mortality and worse prognosis of diabetes after pancreatitis are higher. We predicted that number of recurrences of pancreatitis would be significantly associated with the incidences of metabolic syndrome, abdominal obesity, and post-acute pancreatitis diabetes mellitus., Methods: Patients admitted to our hospital for hypertriglyceridemic acute pancreatitis from 2013-2021 were selected for a cross-sectional study. Statistical analysis methods were used to analyze the effect of recurrences on the long-term prognosis of patients with hypertriglyceridemic acute pancreatitis., Results: In this study, 101 patients with hypertriglyceridemic acute pancreatitis were included: 60 (59.41%) in the recurrent acute pancreatitis group and 41 (40.59%) in the only one episode of acute pancreatitis group. Among all hypertriglyceridemic acute pancreatitis patients, approximately 61.4% were diagnosed with abdominal obesity, 33.7% of patients are diagnosed with metabolic syndrome, 34.7% of patients are diagnosed with diabetes mellitus, and 21.8% of patients are diagnosed with post-acute pancreatitis diabetes mellitus. Recurrent acute pancreatitis were independent risk factors for post-acute pancreatitis diabetes mellitus in patients with hypertriglyceridemic acute pancreatitis (odds ratio [OR] = 3.964, 95% confidence interval [CI] = 1.230-12.774) and the risk of post-acute pancreatitis diabetes mellitus in patients with three or more recurrent episodes was 6.607 times higher than that in patients without recurrent episodes (OR = 6.607, 95% CI = 1.412-30.916)., Conclusions: Recurrence is an independent risk factor for the development of post-acute pancreatitis diabetes mellitus and is significantly associated with the number of recurrences., (© 2023. The Author(s).)

Background: The anesthetic states are accompanied by functional alterations. However, the dose-related adaptive alterations in the higher-order network under anesthesia, e. g. default mode network (DMN), are poorly revealed., Methods: We implanted electrodes in brain regions of the rat DMN to acquire local field potentials to investigate the perturbations produced by anesthesia. Relative power spectral density, static functional connectivity (FC), fuzzy entropy of dynamic FC, and topological features were computed from the data., Results: The results showed that adaptive reconstruction was induced by isoflurane, exhibiting reduced static and stable long-range FC, and altered topological features. These reconstruction patterns were in a dose-related fashion., Conclusion: These results might impart insights into the neural network mechanisms underlying anesthesia and suggest the potential of monitoring the depth of anesthesia based on the parameters of DMN., (© 2023. The Author(s).)

Background: Formyl peptide receptor 2 (Fpr2) plays a crucial role in colon homeostasis and microbiota balance. Commensal E. coli is known to promote the regeneration of damaged colon epithelial cells. The aim of the study was to investigate the connection between E. coli and Fpr2 in the recovery of colon epithelial cells., Results: The deficiency of Fpr2 was associated with impaired integrity of the colon mucosa and an imbalance of microbiota, characterized by the enrichment of Proteobacteria in the colon. Two serotypes of E. coli, O22:H8 and O91:H21, were identified in the mouse colon through complete genome sequencing. E. coli O22:H8 was found to be prevalent in the gut of mice and exhibited lower virulence compared to O91:H21. Germ-free (GF) mice that were pre-orally inoculated with E. coli O22:H8 showed reduced susceptibility to chemically induced colitis, increased proliferation of epithelial cells, and improved mouse survival. Following infection with E. coli O22:H8, the expression of Fpr2 in colon epithelial cells was upregulated, and the products derived from E. coli O22:H8 induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency increased susceptibility to chemically induced colitis, delayed the repair of damaged colon epithelial cells, and heightened inflammatory responses. Additionally, the population of E. coli was observed to increase in the colons of Fpr2 -/- mice with colitis., Conclusion: Commensal E. coli O22:H8 stimulated the upregulation of Fpr2 expression in colon epithelial cells, and the products from E. coli induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency led to an increased E. coli population in the colon and delayed recovery of damaged colon epithelial cells in mice with colitis. Therefore, Fpr2 is essential for the effects of commensal E. coli on colon epithelial cell recovery., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Brucellosis is a chronic zoonotic disease, and Ningxia is one of the high prevalence regions in China. To mitigate the spread of brucellosis, the government of Ningxia has implemented a comprehensive prevention and control plan (2022-2024). It is meaningful to quantitatively evaluate the accessibility of this strategy., Methods: Based on the transmission characteristics of brucellosis in Ningxia, we propose a dynamical model of sheep-human-environment, which coupling with the stage structure of sheep and indirect environmental transmission. We first calculate the basic reproduction number [Formula: see text] and use the model to fit the data of human brucellosis. Then, three widely applied control strategies of brucellosis in Ningxia, that is, slaughtering of sicked sheep, health education to high risk practitioners, and immunization of adult sheep, are evaluated., Results: The basic reproduction number is calculated as [Formula: see text], indicating that human brucellosis will persist. The model has a good alignment with the human brucellosis data. The quantitative accessibility evaluation results show that current brucellosis control strategy may not reach the goal on time. "Ningxia Brucellosis Prevention and Control Special Three-Year Action Implementation Plan (2022-2024)" will be achieved in 2024 when increasing slaughtering rate [Formula: see text] by 30[Formula: see text], increasing health education to reduce [Formula: see text] to 50[Formula: see text], and an increase of immunization rate of adult sheep [Formula: see text] by 40[Formula: see text]., Conclusion: The results demonstrate that the comprehensive control measures are the most effective for brucellosis control, and it is necessary to further strengthen the multi-sectoral joint mechanism and adopt integrated measures to prevention and control brucellosis. These results can provide a reliable quantitative basis for further optimizing the prevention and control strategy of brucellosis in Ningxia., (© 2023. The Author(s).)

Background: There is no standard reconstruction method following proximal gastrectomy, of which gastroesophageal reflux and anastomotic complications are of great concern. Though several techniques have been devised to overcome these postoperative complications, such as double tract reconstruction, double-flap technique and side overlap fundoplication by Yamashita, none of them is considered a perfect solution. Herein, we designed a novel method of esophagogastrostomy after laparoscopic proximal gastrectomy (LPG), named right-sided overlap and single-flap valvuloplasty (ROSF)., Methods: Between March 2021 and December 2021, 20 consecutive patients underwent LPG-ROSF at Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University. Surgical outcomes and postoperative complications were recorded. All patients were followed-up until December 2022. Endoscopy and assessment of gastrointestinal symptoms were performed 1 year after surgery. Nutrition-related parameters including total body weight, hemoglobin, lymphocyte count, serum total protein, serum albumin and serum prealbumin were evaluated 1 year after surgery and compared with those before surgery., Results: The mean surgery time and anastomosis time was 285.3 ± 71.3 and 61.3 ± 11.2 min respectively. None of the patients had gastrointestinal early postoperative complications. Symptomatic reflux was observed in one patient (5%) while reflux esophagitis (Los Angeles Grade A) was observed in another patient (5%). Four patients (20%) had mild dysphagia (Visick score = II) but none of them had anastomotic stenosis. There were no significant changes in nutritional status postoperatively., Conclusions: ROSF can be safely performed after LPG and has satisfactory outcomes in preventing reflux and stenosis, and maintaining nutritional status. This technique requires further validation., (© 2023. The Author(s).)

Background: Influenza vaccination is the key to prevent influenza-related disease, especially among high-risk populations. However, influenza vaccine uptake in China is low. This secondary analysis of a quasi-experimental trial aimed to understand factors associated with influenza vaccine uptake among children and older people stratified by funding context., Methods: A total of 225 children (aged 0.5-8 years) and 225 older people (aged 60 years or above) were recruited from three clinics (rural, suburban and urban) in Guangdong Province. Participants were allocated into two groups based on funding contexts: a self-paid group (N = 150, 75 children and 75 older adults) in which participants paid full price for their vaccination; and a subsidized group (N = 300, 150 children and 150 older adults) in which varying levels of financial support was provided. Univariate and multivariable logistic regressions were conducted stratified by funding contexts., Results: Overall, 75.0% (225/300) of participants in the subsidized group and 36.7% (55/150) in the self-paid group got vaccinated. Older adults had lower vaccination rates than children in both funding groups, while both age groups showed much higher uptake in the subsidized group than in the self-paid group (aOR = 5.96, 95% CI: 3.77-9.42, p = 0.001). In the self-paid group, having prior influenza vaccination history of children (aOR:2.61, 95%CI: 1.06-6.42) or older people (aOR:4.76, 95%CI: 1.08-20.90) was associated with increased influenza vaccine uptake compared to those who had no prior vaccination experiences in the family. While in the subsidized group, participants who got married or lived with partners (aOR = 0.32, 0.10-0.98) had lower vaccination uptake than single ones. Trust in providers' advice (aOR = 4.95, 95%CI:1.99, 12.43), perceived effectiveness of the vaccine (aOR: 12.18, 95%CI: 5.21-28.50), and experienced influenza-like illnesses in the family in the past year (aOR = 46.52, 4.10, 533.78) were associated with higher vaccine uptake., Conclusions: Older people had suboptimal vaccine uptake compared to children in both contexts and need more attention to enhance influenza vaccination. Tailoring interventions to different vaccine funding contexts may help improve influenza vaccination: In self-paid context, motivating people to accept their first ever influenza vaccination may be a promising strategy. In subsidized context, improving public confidence in vaccine effectiveness and providers' advice would be useful., (© 2023. The Author(s).)

Background: Timely screening and referral can improve the outcomes of perinatal depression (PND). However, uptake rates of referral after PND screening are low in China and the reasons are unclear. The aim of this article is to explore the barriers and facilitators for referring women with positive results of PND screening in the Chinese primary maternal health care system., Methods: Qualitative data were collected from four primary health centers located in four different provinces of China. Each of the four investigators conducted 30 days of participant observations in the primary health centers from May to August 2020. Data were collected via participant observations and semi-structured in-depth interviews with new mothers who had positive results of PND screening, their family members, and primary health providers. Two investigators analyzed qualitative data independently. A thematic analysis was conducted, and data were framed using the social ecological model., Results: A total of 870 hours of observation and 46 interviews were carried out. Five themes were identified: individual (new mothers' knowledge of PND, perceived need to seek help), interpersonal (new mothers' attitudes towards providers, family support), institutional (providers' perception of PND, lack of training, time constraints), community (accessibility to mental health services, practical factors), and public policy (policy requirements, stigma)., Conclusions: The likelihood of new mothers accepting PND referral is related to factors in five areas. Intervention strategies can be developed around these themes and may include educating new mothers and their families about PND, training primary health providers to improve their awareness of condition and indication for referral, building mental health support in routine postpartum home visits, and providing support through mobile technology., (© 2023. The Author(s).)

Background: Orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid, OA) and its structural analog o-Orsellinaldehyde, have become widely used intermediates in clinical drugs synthesis. Although the research on the biosynthesis of such compounds has made significant progress, due to the lack of suitable hosts, there is still far from the industrial production of such compounds based on synthetic biology., Results: With the help of genome mining, we found a polyketide synthase (PKS, HerA) in the genome of the Hericium erinaceus, which shares 60% amino acid sequence homology with ArmB from Armillaria mellea, an identified PKS capable of synthesizing OA. To characterize the function of HerA, we cloned herA and heterologously expressed it in Aspergillus oryzae, and successfully detected the production of OA. Subsequently, the introduction of an incomplete PKS (Pks5) from Ustilago maydis containing only three domains (AMP-ACP-R), which was into herA-containing A. oryzae, the resulted in the production of o-Orsellinaldehyde. Considering the economic value of OA and o-Orsellinaldehyde, we then optimized the yield of these compounds in A. oryzae. The screening showed that when maltose was used as carbon source, the yields of OA and o-Orsellinaldehyde were 57.68 mg/L and 15.71 mg/L respectively, while the yields were 340.41 mg/Kg and 84.79 mg/Kg respectively in rice medium for 10 days., Conclusions: Herein, we successfully expressed the genes of basidiomycetes using A. oryzae heterologous host. As a fungus of ascomycetes, which not only correctly splices genes of basidiomycetes containing multiple introns, but also efficiently produces their metabolites. This study highlights that A. oryzae is an excellent host for the heterologous production of fungal natural products, and has the potential to become an efficient chassis for the production of basidiomycete secondary metabolites in synthetic biology., (© 2023. The Author(s).)

Background and Objective: Whether obstructive sleep apnea (OSA) is associated with worse prognosis in patients with acute coronary syndrome (ACS) with or without prior stroke remains unclear. We investigated the association of OSA with cardiovascular events in ACS patients with or without prior stroke., Methods: Between June 2015 and January 2020, we prospectively recruited eligible ACS patients who underwent cardiorespiratory polygraphy during hospitalization. We defined OSA as an apnea hypopnea index (AHI) ≥ 15 events/hour. The primary composite end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure., Results: Among 1927 patients enrolled, 207 patients had prior stroke (10.7%) and 1014 had OSA (52.6%). After a mean follow-up of 2.9 years, patients with stroke had significantly higher risk of MACCEs than those without stroke (hazard ratio [HR]:1.49; 95% confidence interval [CI]: 1.12-1.98, P = 0.007). The multivariate analysis showed that patients with OSA had 2.0 times the risk of MACCEs in prior stroke group (41 events [33.9%] vs 18 events [20.9%]; HR:2.04, 95% CI:1.13-3.69, P = 0.018), but not in non-prior stroke group (186 events [20.8%] vs 144 events [17.4]; HR:1.21, 95% CI 0.96-1.52, P = 0.10). No significant interaction was noted between prior stroke and OSA for MACCE (interaction P = 0.17)., Conclusions: Among ACS patients, the presence of OSA was associated with an increased risk of cardiovascular events in patients with prior stroke. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS and prior stroke are warranted. Trial registration Clinicaltrials.gov identifier NCT03362385., (© 2023. The Author(s).)

Background: The COVID-19 pandemic has impacted endoscopic training of the Narrow Band Imaging International Colorectal Endoscopic (NICE) classification, which could accurately predict pathology of colorectal polyps. This study aimed to evaluate the diagnostic performance by trainees of self-driven training vs. interactive training in the prediction of colorectal polyp histology., Methods: This was a prospective randomized controlled study at five academic centers from January 1, 2021 to May 31, 2021. Trainees with no previous formal training of narrow band imaging or blue light imaging for prediction of colorectal polyp histology were randomly allocated to the self-driven training group or interactive training group. Before and after the training, all trainees were given 20 selected cases of colorectal polyp for testing. Their diagnostic performance was analyzed., Results: Overall, the two training groups showed similar accuracy of NICE classification (79.3% vs. 78.1%; P = 0.637), vessel analysis (77.8% vs. 77.6%, P = 0.939), and surface pattern analysis (78.1% vs. 76.9%, P = 0.616). The accuracy of color analysis in the interactive training group was better (74.4% vs. 80.0%, P = 0.027). For high-confidence predictions, the self-driven training group showed higher accuracy of NICE classification (84.8% vs. 78.7%, P < 0.001) but no difference for analysis of color (79.6% vs. 81.0%), vessel pattern (83.0% vs. 78.5%), and surface pattern (81.8% vs. 78.5%)., Conclusions: Overall, self-driven training showed comparable accuracy of NICE classification, vessel pattern, and surface pattern to interactive training, but lower accuracy of color analysis. This method showed comparable effectiveness and is more applicable than interactive training. It is worth spreading during the COVID-19 pandemic. Trial registration Name of the registry: Chinese Clinical Trial Registry, Trial registration number: ChiCTR2000031659, Date of registration: 06/04/2020, URL of trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=51994., (© 2023. The Author(s).)

Background: Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9-18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15-18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China., Methods: This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series., Discussion: This study will investigate an innovative pay-it-forward strategy's effectiveness and economic costs to improve HPV vaccination among 15-18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee., Trial Registration: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200055542. Registered on 11 January 2022., (© 2023. The Author(s).)

Background: After stroke, an abnormal gait pattern gradually leads to knee pain and joint lesions, resulting the gait instability. However, the correlation between the knee hyperextension and gait pattern, the meniscus volume, and the water content of meniscus in paretic and non-paretic legs has not been fully investigated. Moreover, most of physicians tend to ignore this knee hyperextension. This study attempted to emphasize the importance of knee hyperextension using gait analysis and Magnetic resonance imaging (Trial registration number ChiCTR2000039641, date of registration 04/11/2020)., Methods: Eight patients with chronic hemiplegic (6 male, 2 female) volunteered to participate in this study. Participants was recruited if they had a hemiplegia following a stroke occurring more than 6 months, had an ability to walk 10 m without aids, had a Function Ambulation Category level at least 3 and above, and had a hemiplegic lower extremity identified as Brunnstrom state III or above identification. The spatial-temporal gait parameters and kinematic parameters in the paretic and the non-paretic legs and the percentage of free water content in deep and shallow layers., Results: Longer time since hemiplegia led to larger angles of knee hyperextension (R = 0.56, p = 0.016), larger angles of knee hyperextension led to more tears in meniscus (R =  - 0.53, - 0,57 and - 0.70), and larger angles of knee hyperextension decreased water content of the lateral meniscus in the non-paretic leg (R =  - 0.91) but increased water content of the medial meniscus (R = 0.53 and 0.63)., Conclusions: The knee hyperextension could not be ignored by physicians and needed to be diagnosed and treated as early as possible, the time since hemiplegia could be an indicator of sign of knee hyperextension., (© 2023. The Author(s).)

Background: Consumption of high fructose corn syrup sweetened drinks and diet soft drinks has increased in the United States. However, the relationship between the intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium has been scarcely studied. Our objective is to evaluate the relation between intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium, and explore the possible effect modifiers in a nationally representative sample of adults from the United States., Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey 2003-2006. The study participants included 6989 adults aged ≥18 years. Using survey-weighted generalized linear regression analyses, we investigated the relationship between high fructose corn syrup sweetened drink, diet soft drink consumption, and serum sodium. Consumption of high fructose corn syrup sweetened drinks and diet soft drinks was evaluated through a food-frequency questionnaire., Results: Serum sodium levels increased as high fructose corn syrup sweetened drink intake increased. Serum sodium levels were higher in participants in the highest high fructose corn syrup sweetened drink consumption quantile, compared with those in the lowest high fructose corn syrup sweetened drink intake quantile (p = 0.020). The multivariate betas for serum sodium, according to the corresponding high fructose corn syrup sweetened drink intake quantiles, were 0.16, 0.19, and 0.21, respectively (P for trend = 0.051). We found no relationship between diet soft drink consumption and serum sodium after adjustment of confounding. (multivariate P > 0.05)., Conclusion: There was a a step-wise increase in serum sodium concentration with increasing consumption of HFCS sweetened beverages. Even moderate HFCS sweetened soft drink intake was associated with an elevated serum sodium level - a risk factor for hypertension., (© 2022. The Author(s).)

Background: Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients., Methods: From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses., Results: Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients., Conclusions: The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients., Trial Registration: Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017., (© 2022. The Author(s).)

Background: Gallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC., Methods: We analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer., Results: We found that high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 inhibited the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and triggering autophagy in NOZ and GBC-SD cells. Indeed, XPO1 inhibitor KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo., Conclusion: XPO1 may be a promising prognostic indicator for GBC, and KPT-330 appears to be a potential drug for treating GBC effectively and safely., (© 2022. The Author(s).)

Background: Multiprotein bridging factor 1 (MBF1) is a crucial transcriptional coactivator in animals, plants, and some microorganisms, that plays a necessary role in growth development and stress tolerance. Zanthoxylum armatum is an important perennial plant for the condiments and pharmaceutical industries, whereas the potential information in the genes related to stress resistance remains poorly understood in Z. armatum.  RESULTS: Herein, six representative species were selected for use in a genome-wide investigation of the MBF1 family, including Arabidopsis thaliana, Oryza sativa, Populus trichocarpa, Citrus sinensis, Ginkgo biloba, and Z. armatum. The results showed that the MBF1 genes could be divided into two groups: Group I contained the MBF1a and MBF1b subfamilies, and group II was independent of the MBF1c subfamily.. Most species have at least two different MBF1 genes, and MBF1c is usually an essential member. The three ZaMBF1 genes were respectively located on ZaChr26, ZaChr32, and ZaChr4 of Zanthoxylum chromosomes. The collinearity were occurred between three ZaMBF1 genes, and ZaMBF1c showed the collinearity between Z. armatum and both P. trichocarpa and C. sinensis. Moreover, many cis-elements associated with abiotic stress and phytohormone pathways were detected in the promoter regions of MBF1 of six representative species. The ERF binding sites were the most abundant targets in the sequences of the ZaMBF1 family, and some transcription factor sites related to floral differentiation were also identified in ZaMBF1c, such as MADS, LFY, Dof, and AP2. ZaMBF1a was observed to be very highly expressed in 25 different samples except in the seeds, and ZaMBF1c may be associated with the male and female floral initiation processes. In addition, expression in all the ZaMBF1 genes could be significantly induced by water-logging, cold stress, ethephon, methyl jasmonate, and salicylic acid treatments, especially in ZaMBF1c., Conclusion: The present study carried out a comprehensive bioinformatic investigation related to the MBF1 family in six representative species, and the responsiveness of ZaMBF1 genes to various abiotic stresses and phytohormone inductions was also revealed. This work not only lays a solid foundation to uncover the biological roles of the ZaMBF1 family in Z. armatum, but also provides some broad references for conducting the MBF1 research in other plants., (© 2022. The Author(s).)

Background: Alpha‑fetoprotein-producing gastric cancer (AFPGC) is a rare type of gastric cancer with a high rate of metastasis and poor prognosis. Despite substantial progress in the treatment of many solid tumors, there are no reports of the safety and effectiveness of immune checkpoint inhibitors in combination with antiangiogenesis agents for AFPGC patients who have proficient mismatch repair., Case Presentation: We describe a 69-year-old man who was diagnosed with metastatic AFPGC. After progression to chemotherapy resistance, tislelizumab combined with apatinib was administered, although the patient's gastroscopic pathology showed proficient mismatch repair. After three cycles of therapy, partial remission (reduced by 56%) was obtained, and the quality of life improved significantly. Surprisingly, after more than 1 year of continuous application of the combination treatment regimen, both the primary and metastatic tumors in this patient eventually disappeared, which obtained complete remission without surgery. The patient has had a progression-free survival of more than 24 months and is still continuing to benefit., Conclusions: This case is the first example of effective treatment of AFPGC with tislelizumab combined with apatinib. The outcomes of this case suggest a highly effective and tolerable therapeutic strategy for microsatellite-stabilized AFPGC., (© 2022. The Author(s).)