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Ting-Ting Yang,1,&ast; Ze-Yi Wang,1,&ast; Ze-Xin Fan,1 Bo-Yi Yuan,1 Lin Ma,1 Jian-Feng Lu,1 Pen-Ju Liu,1 Yang He,2 Guang-Zhi Liu1 1Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China; 2Department of Neurology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang-Zhi Liu, Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China, Tel +86-10-64456149, Fax +86-10-64456119, Email guangzhi2002@hotmail.comObjective: This study aimed to initially investigate the efficacy and safety of low-dose tocilizumab combined with glucocorticoid for the treatment of very-late-onset myasthenia gravis (VLOMG).Methods: We conducted a retrospective study in VLOMG patients who were administered intravenous methylprednisolone therapy and subsequently received low-dose oral corticosteroid, in combination with intravenous injection of tocilizumab given once every month for three months.Results: Five patients (mean age 75.0 ± 4.5 years) were included, and all of them were new-onset, and anti-acetylcholine receptor (AChR) antibody-positive generalized MG. The Quantitative Myasthenia Gravis Scale (QMGS) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before treatment were 15.4 ± 4.3 and 9.6 ± 2.3, respectively, and they exhibited a continuously decreasing trend after the first, second, and third injection of tocilizumab until 6 months after treatment. At 6 months post-treatment, the QMGS and MG-ADL scores were 5.0 ± 2.9 and 2.0 ± 1.2, respectively, and the difference between scores at baseline and 6-month follow-up was significant (P = 0.005 and P < 0.0001, respectively). No serious adverse drug reactions were reported in any patient during the study period.Discussions and Conclusion: The therapeutic efficacy of tocilizumab in VLOMG remains uncertain. The results from our study support the efficacy and safety of this combination treatment option for VLOMG, and strongly suggests the therapeutic potential of tocilizumab in VLOMG. However, considering the limitation of retrospective nature and small sample size in this study, prospective randomized controlled studies including a larger sample size of selected patients are needed to validate our results.Keywords: very late-onset myasthenia gravis, immunotherapy, tocilizumab, glucocorticoid

Peng Ju Liu,1 Liangkun Ma,2 Rui Li,1 Yanping Liu1 1Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yanping Liu, Tel/Fax +86-10-69155535, Email liuyp1227@vip.sina.comPurpose: The role of imbalanced one-carbon nutrients in gestational diabetes mellitus (GDM) risk has garnered significant interest, yet existing studies yield inconsistent results. Our objective was to assess whether the association between an unbalanced ratio of folate to vitamin B12 and GDM risk is influenced by the status of other micronutrients.Methods: This cohort study included 366 singleton-pregnancy Han women enrolled at the Shunyi District Maternal and Child Health Hospital in Beijing, China. During the first trimester of pregnancy, we measured red blood cell (RBC) folate, serum levels of vitamin B12, vitamin D, and selenium. We examined the association between the imbalanced status of RBC folate and vitamin B12 and GDM risk using logistic regression, stratified by serum selenium or vitamin D status.Results: Among the 366 women, 67 (18.3%) were diagnosed with GDM, 201 (54.9%) had vitamin D deficiency, and 245 (66.9%) had selenium deficiency. Overall, women with higher RBC folate/vitamin B12 ratios did not exhibit a significantly higher risk of GDM compared to those in reference tertile (all P > 0.05). Subsequently, we divided women into deficient and non-deficient groups based on serum selenium or vitamin D levels. In women with selenium deficiency, those in the highest tertile of the RBC folate/vitamin B12 ratio had the highest odds of GDM [OR: 3.40 (1.16– 9.97), P=0.026] after adjusting for covariates. However, similar findings were not observed in pregnancies with normal selenium status. Irrespective of vitamin D status, women with higher RBC folate/vitamin B12 ratios did not exhibit a significantly increased risk of GDM.Conclusion: Micronutrient deficiencies are common in early pregnancy. Women with a higher folate/vitamin B12 ratio coupled with selenium deficiency in early pregnancy have a higher GDM risk. These findings underscore the importance of micronutrient assessment in early pregnancy and subsequent interventions for micronutrient deficiencies.Keywords: gestational diabetes mellitus, folate, vitamin B12, early pregnancy, selenium deficiency

Ming Tang,1,2 Peng-Jie Liu,3 Bing Yue,2 Xuan-Tao Yang,1 Guang-Yong Chen2 1Department of Pathology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, People’s Republic of China; 2Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 3Department of Nuclear Medicine, The Tumor Hospital of Yunnan Province, Kunming, 650118, People’s Republic of ChinaCorrespondence: Guang-Yong ChenDepartment of Pathology, Beijing Friendship Hospital, Capital Medical University, No. 95 of Yongan Street, Xicheng District, Beijing, 100050, People’s Republic of ChinaTel +86 10 6301 4411Fax +86 10 6301 6616Email gycdr_sun06@163.comObjective: This study aims to explore the correlation between the expression of mutant p53 protein and cellular atypia in early differentiated gastric adenocarcinoma (DGA).Methods: A total of 107 cases of early DGA samples resected by endoscopic submucosal dissection (ESD) were collected from the Pathology Department of Beijing Friendship Hospital from January 2018 to December 2019. The EnVision two-step immunohistochemical method was used to detect the expression of mutant p53 protein in these cancer tissues, and the correlation with cell atypia was analyzed.Results: In early DGA tissues, the expression rate of mutant p53 protein was significantly higher than in normal gastric mucosa (P < 0.01). However, the expression of mutant p53 protein was not correlated to age or gender (P > 0.05) but to the location of the tumor, depth of invasion, and degree of differentiation (P < 0.01). The expression of mutant p53 protein was closely correlated to cell atypia. Furthermore, this was weakly positive in low-grade atypical adenocarcinoma but strongly positive or negative in high-grade atypical adenocarcinoma, and there was a significant difference between these two (P < 0.01).Conclusion: Mutant p53 protein is highly expressed in early DGA, which can be used as an auxiliary index for the diagnosis of early gastric cancer. The different expression patterns of mutant p53 protein in high-grade and low-grade atypical gastric cancers suggest that these may have different genetic changes.Keywords: early gastric cancer, cell atypia, mutation, P53 protein

Peng Ju Liu,1 Hui Ping Lou,2 Yan Ning Zhu3 1Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Medical Examination Center, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Peng Ju LiuDepartment of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, #1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 10-69155550Fax +86 10-69155551Email lpjjia@126.comBackground: The hypertriglyceridemic waist phenotype (HWP) has exhibited a strong association with metabolic syndrome, a condition closely linked with nonalcoholic fatty liver disease (NAFLD). However, no study has investigated whether the HWP can accurately predict NAFLD among premenopausal and postmenopausal women or whether alternative anthropometric indexes could replace waist circumference (WC) in the HWP. We examined the power of phenotypes combining triglyceride (TG) levels with anthropometric indexes such as body mass index (BMI), WC, waist-to-hip ratio, waist-to-height ratio, and percent body fat, to detect NAFLD among premenopausal and postmenopausal women.Methods: We conducted a cross-sectional study of 1125 premenopausal women and 654 postmenopausal women who had received an annual health checkup. For all the participating women, we measured both anthropometric and biochemical indexes, such as serum lipid levels. NAFLD diagnoses were made on the basis of abdominal ultrasonography findings. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the indicators’ ability to detect NAFLD.Results: Among the indicators of hepatic steatosis, the combined phenotypes of TG level (≥ 1.50 mmol/L) and BMI (≥ 24.0 kg/m2) exhibited the largest AUC (0.841, 95%confidence interval [CI] 0.812– 0.871, P< 0.001) for premenopausal women, whereas WC alone exhibited the highest predictive potential (0.765, 95% CI 0.729– 0.801, P< 0.001) for postmenopausal women.Conclusion: Out of all the phenotypes combining a single anthropometric index with TG level or WC and TG level, the combination of TG level and BMI was the best indicator of NAFLD for premenopausal women. For screening NAFLD in postmenopausal women, WC alone was superior to all other indicators.Keywords: nonalcoholic fatty liver disease, hepatic steatosis, anthropometric index, hypertriglyceridemic waist phenotype, menopause

Peng Ju Liu,1 Hui Ping Lou,2 Yan Ning Zhu3 1Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Medical Examination Center, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Peng Ju Liu Tel +86-10-69155550Fax +86-10-69155551Email lpjjia@126.comBackground: It has been suggested that hypertriglyceridemic waist (HW) phenotype is strongly associated with metabolic syndrome (MetS); however, there are very limited studies integrating triglyceride (TG) and waist circumference (WC) into a continuous variable to investigate the predictive power of this phenotype. Inspired from the triglyceride glucose index (TyG), we developed an integrated continuous index termed waist-triglyceride index (WTI) which was calculated as Ln [TG (mg/dl) WC (cm)/2].Objective: We aimed to examine the potential of WTI in screening for MetS by comparing this quantitative index with the qualitative HW phenotype and other frequently used indices.Methods: A cross-sectional study was conducted in a total of 3460 non-diabetic adults who participated in an annual health checkup. MetS was defined by the update National Cholesterol Education Program/Adult Treatment Panel ш criteria for Asian Americans. Receiving operating characteristic (ROC) curve and areas under the curve (AUC) were employed to evaluate the performance of the involved indices in screening for MetS. Statistical differences among the AUC values of the indices were compared.Results: In both genders, the AUC value of WTI, TyG or HW phenotype was markedly larger than that of each anthropometric index alone. In men, there were no statistical differences in the AUC values among WTI, TyG and HW phenotype, whereas in women, the AUC value of WTI was significantly larger than that of HW phenotype [difference between area (DBA): 0.042, 95% CI: 0.0224– 0.0617, P < 0.0001] and was nominally and significantly smaller than that of TyG (DBA: 0.00646, 95% CI: 0.000903– 0.012, P = 0.0227).Conclusion: Our results suggest that there are discriminatory performance between the WTI and HW phenotype in the detection of MetS in women rather than in men. Appropriate markers for screening MetS in population study should be considered according to the genders.Keywords: metabolic syndrome, hypertriglyceridemic, waist circumference, triglyceride glucose index, hypertriglyceridemic waist phenotype

Peng Ju Liu,1 Yanping Liu,1 Liangkun Ma,2 Ai Min Yao,3 Xiao Yan Chen,4 Yi Xuan Hou,5 Li Ping Wu,5 Liang Yu Xia6 1Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Gynaecology and Obstetrics, Shunyi District Maternal and Child Health Hospital, Beijing, People’s Republic of China; 4Department of Gynaecology and Obstetrics, Quanzhou Maternal and Child Health Hospital, Fujian, People’s Republic of China; 5Peking Union Medical College School of Nursing, Beijing, People’s Republic of China; 6Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yanping Liu Tel +86-10-69159081Fax +86-10-69155551Email liuyp1227@vip.sina.comBackground/Aims: To investigate the potential of maternal first-trimester triglyceride (TG) to high-density lipoprotein cholesterol (TG/HDL-c) ratio, triglyceride glucose index (TyG) and total cholesterol (TC)/HDL-c to predict the risk of later gestational diabetes mellitus (GDM) and large for gestational age (LGA) newborn in Chinese women.Methods: We included 352 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Fasting glucose and plasma lipid profiles including TG, TC, HDL-c, and low-density lipoprotein cholesterol (LDL-c) were measured in the first trimester. A binary logistic regression analysis was performed to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and LGA according to tertiles of those indices, respectively. Receiver-operating characteristic curve (ROC) and areas under the curve (AUC) were employed to evaluate the ability of those indices to predict the risk of GDM and LGA infants, and differences in the AUC values between them were compared.Results: Women with the top tertile of TG/HDL-c or TyG other than TC/HDL-c had a significantly higher risk of GDM (ORTG/HDL-c=2.388, 95% CI 1.026– 5.467; ORTyG=3.535, 95% CI 1.483– 8.426, respectively) and LGA infant delivery (ORTG/HDL-c=3.742, 95% CI 1.114– 12.569; ORTyG=3.011, 95% CI 1.012– 8.962, respectively) than women with the lowest tertile of TG/HDL-c or TyG after adjusting for confounders. The AUC of TG/HDL-c and TyG to detect GDM was 0.664 (95% CI 0.595– 0.733) and 0.686 (95% CI 0.615– 0.756), respectively, and that to detect LGA was 0.646 (95% CI 0.559– 0.734) and 0.643 (95% CI 0.552– 0.735), respectively (all P < 0.01). There were no statistical differences between TG/HDL-c and TyG in the ability of predicting the risk of GDM or LGA infants.Conclusion: Maternal first-trimester TG/HDL-c and TyG are both good indicators in predicting the risk of later GDM and LGA newborn, and it may be useful to evaluate them in early pregnancy.Keywords: gestational diabetes, triglyceride/HDL-c ratio, triglyceride glucose index, large for gestational age infant

Peng Ju Liu,1 Yanping Liu,1,* Liangkun Ma,2,* Ai Min Yao,3 Xiao Yan Chen,4 Yi Xuan Hou,5 Li Ping Wu,5 Liang Yu Xia6 1Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing 100730, People’s Republic of China; 3Department of Gynaecology and Obstetrics, Shunyi District Maternal and Child Health Hospital, Beijing, People’s Republic of China; 4Department of Gynaecology and Obstetrics, Quanzhou Maternal and Child Health Hospital, Fujian, People’s Republic of China; 5Peking Union Medical College School of Nursing, Beijing, People’s Republic of China; 6Department of Clinical Laboratory, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanping Liu; Liangkun Ma Tel +86-10-69159081Fax +86-10-69155551Email liuyp1227@vip.sina.com; maliangkun@pumch.cnPurpose: Red blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China.Methods: A total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms.Results: Participants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013– 6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms.Conclusion: Higher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.Keywords: gestational diabetes mellitus, folic acid, folate, red blood cell folate, methylenetetrahydrofolate reductase, MTHFR

Peng Ju Liu,1,* Yan Ping Liu,1,* Hui Kun Qin,2 Tong Xing,2 Shan Shan Li,1 Yuan Yuan Bao1 1Departments of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Nutrition, Pinggu Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background/aims: Low glycemic index (GI) diets may have beneficial effects on glycemic control and serum lipid levels in patients with type 2 diabetes, but whether its effect is affected by polymorphisms of genes associated with lipid metabolism remains unclear. This study investigated whether the effects of a low-GI diet on serum lipids and glycemic control in patients with diabetes are associated with polymorphisms of FABP2 Ala54Thr (rs1799883).Methods: A retrospective study was conducted involving 165 patients with type 2 diabetes mellitus (T2DM) who participated in two completed trials. Parameters reflecting the glycemic control, inflammatory factors, and fasting plasma lipids before and after intervention were measured, and the polymorphism of rs1799883 for each participant was genotyped using a MassARRAY. Differences between the genotypes of rs1799883 before or after the intervention were compared, and changes in the lipid profiles, glycemic control, inflammatory profiles, and dietary intake from baseline were analyzed using an analysis of covariance (generalized linear model).Results: When the data were analyzed as a whole, after 4–5 weeks of similar low-GI diet intervention, we found that the decrease of triglycerides (TG) in the homozygous Ala54 carriers was more significant than that in the Thr54 allele carriers ([−0.58±1.24] vs [−0.14±1.08], P=0.015) with the adjustment for potential confounding factors; furthermore, compared with the Thr54 carriers, there was a significant trend in the decrease of total cholesterol (TC) in the homozygous Ala54 carriers (P=0.057). Subgroup analysis revealed that in women the homozygous Ala54 carriers exhibited a significant decrease of serum TG, TC, fasting blood glucose, and glycated albumin in women, but this was not noted in men.Conclusion: The effect of FABP2 Ala54Thr polymorphism on response to blood lipids and glycemic control in low-GI diets is associated with gender among Han Chinese patients with T2DM. Keywords: type 2 diabetes mellitus, plasma lipids, fatty acid-binding protein 2, single-nucleotide polymorphism, low glycemic index diet

Context: The beneficial effects of probiotic supplementation on bone health in postmenopausal women require further validation., Objective: This study systematically reviewed and conducted a meta-analysis of randomized controlled trials (RCTs) to assess the relationship between probiotic supplementation and changes in bone mineral density (BMD) and bone turnover markers (BTMs) among postmenopausal women., Methods: A systematic search was conducted across four databases to retrieve data on lumbar spine BMD, hip BMD, collagen type 1 cross-linked C-telopeptide (CTX), receptor activator of nuclear factor-κB ligand (RANKL), osteocalcin (OC), osteoprotegerin (OPG), N-terminal propeptide of type 1 procollagen (P1NP), and bone-specific alkaline phosphatase (BALP) in postmenopausal women. Eligible RCTs were quantitatively analyzed using random-effects meta-analyses. Additional analyses, including subgroup, sensitivity, and meta-regression analyses, were performed., Results: Twelve RCTs involving 1183 postmenopausal women were included. Compared with the control group, postmenopausal women who received probiotic supplementation showed significantly greater BMD in both the lumbar spine (standardized mean difference [SMD] = 0.60, 95% confidence interval [CI] 0.14 to 1.05) and the hip (SMD = 0.74, 95%CI 0.15 to 1.33). Additionally, probiotic supplementation was associated with reduced levels of CTX (SMD = -1.51, 95%CI -1.88 to -0.41) and BALP (SMD = -1.80, 95%CI -2.78 to -0.81). No significant differences were found between the probiotic and control groups in terms of other BTMs. Subgroup analyses revealed that the increase in BMD due to probiotic supplementation was more significant in postmenopausal women with osteopenia than in those with osteoporosis. The meta-analysis results for both lumbar spine and hip BMD remained robust after conducting sensitivity analyses and meta-regressions., Conclusion: Supplementation with probiotics may increase BMD among postmenopausal women, with stronger evidence in women with osteopenia than osteoporosis. Further RCTs are suggested to confirm and refine these findings., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024576764., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wei and Liu.)

Colorectal cancer (CRC) is a common cancer worldwide with an increasing annual incidence. Cancer stem cells (CSCs) play important roles in the occurrence, development, recurrence, and metastasis of CRC. The molecular mechanism regulating the development of colorectal CSCs remains unclear. The discovery of human induced pluripotent stem cells (hiPSCs) through somatic cell reprogramming has revolutionized the fields of stem cell biology and translational medicine. In the present study, we converted hiPSCs into cancer stem-like cells by culture with conditioned medium (CM) from CRC cells. These transformed cells, termed hiPSC-CSCs, displayed cancer stem-like properties, including a spheroid morphology and the expression of both pluripotency and CSC markers. HiPSC-CSCs showed tumorigenic and metastatic abilities in mouse models. The epithelial-mesenchymal transition phenotype was observed in hiPSC-CSCs, which promoted their migration and angiogenesis. Interestingly, upregulation of C-MYC was observed during the differentiation of hiPSC-CSCs. Mechanistically, CREB binding protein (CBP) bound to the C-MYC promoter, while histone deacetylase 1 and 3 (HDAC1/3) dissociated from the promoter, ultimately leading to an increase in histone acetylation and C-MYC transcriptional activation during the differentiation of hiPSC-CSCs. Pharmacological treatment with a CBP inhibitor or abrogation of CBP expression with a CRISPR/Cas9-based strategy reduced the stemness of hiPSC-CSCs. This study demonstrates for the first time that colorectal CSCs can be generated from hiPSCs. The upregulation of C-MYC via histone acetylation plays a crucial role during the conversion process. Inhibition of CBP is a potential strategy for attenuating the stemness of colorectal CSCs., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The authors declare that all methods were performed in accordance with the relevant guidelines and regulations. The procedures for collecting human blood samples were approved by the Institutional Review Board of the National Taiwan University Hospital. Signed informed consent was obtained from all participants. Additionally, the authors have obtained written informed consent for publication of the images., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Although lifestyle interventions are recommended as the frontline therapeutic strategy for women with gestational diabetes mellitus (GDM), the optimal dietary regimen or form of exercise has yet to be definitively established. We aimed to compare the effectiveness of lifestyle therapies for GDM. Four databases (PubMed, Web of Science, EMBASE, and Cochrane Library) were systematically searched by multiple researchers for randomized controlled trials (RCTs). RCTs comparing lifestyle therapies to treat GDM with control or another treatment were included. Data extraction and synthesis were performed, estimating mean differences (MDs) or relative risk (RR) through pair-wise and network meta-analysis with a randomized or fixed-effects model when appropriate. The primary outcomes were maternal glucose control, birth weight of newborns, macrosomia and preterm birth rate, and rate of need for insulin therapy. In total, 39 trials with information obtained from 2712 women assessed 15 treatments. After sensitivity analysis, we confirmed the dietary approaches to stop hypertension (DASH) diet [MD: -11.52; 95% credible intervals (CrIs): -14.01, -9.07, very low certainty of evidence (CoE)] and low glycemic index (GI) diets (MD: -6.3; 95% CrI: -9.9, -2.7, low CoE) have shown significant advantages in fasting plasma glucose and 2-h postprandial glucose control, respectively. Furthermore, the DASH diet and resistance exercise reduced insulin requirements independently by 71% (95% CrI: 52%, 84%) and 67% (95% CrI: 48%, 85%), respectively. Additionally, both the DASH (MD: -587.6; 95% CrI: -752.12, -421.85, low CoE) and low GI diets (MD: -180.09, 95% CrI: -267.48, -94.65, low CoE) reduced birth weight significantly, with the DASH diet also demonstrating effects in reducing macrosomia by 89% (95% CrI: 53%, 98%) and lowering the cesarean section rate by 46% (95% CI: 27%, 60%). However, exercise did not affect infant outcomes. Our findings suggest that the DASH diet and low GI diet and resistance exercise may be beneficial for maternal outcomes in pregnancies with GDM. The impact on infants is primarily observed through dietary interventions. Future research, characterized by higher quality and evidence grades, is necessary to complement and substantiate our findings. This study was registered with PROSPERO as CRD 42024527587., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) -2.13 kg/m 2 , 95% credible interval (CrI) [-2.7, -1.57]), waist circumference (MD -1.34 cm, 95% CrI [-2.33, -0.35]), total cholesterol (MD -6.55 mg/dL, 95% CrI [-10.61, -2.45]), triglycerides (MD -3.71 mg/dL, 95% CrI [-5.76, -1.67]), leptin (MD -3.99 ng/mL, 95% CrI [-4.68, -3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD -1.21 mg/L, 95% CrI [-1.45, -0.97]). Synbiotics were effective in reducing BMI-z score (MD -0.07, 95% CrI [-0.10, -0.04]) and LDL-C (MD -1.54 mg/dL, 95% CrI [-1.98, -1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings.

Given the growing interest in the metabolic heterogeneity of hepatocellular carcinoma (HCC) and portal vein tumour thrombus (PVTT). This study comprehensively analysed the metabolic heterogeneity of HCC, PVTT, and normal liver samples using multi-omics combinations. A single-cell RNA sequencing dataset encompassing six major cell types was obtained for integrated analysis. The optimal subtypes were identified using cluster stratification and validated using spatial transcriptomics and fluorescent multiplex immunohistochemistry. Then, a combined index based meta-cluster was calculated to verify its prognostic significance using multi-omics data from public cohorts. Our study first depicted the metabolic heterogeneity landscape of non-malignant cells in HCC and PVTT at multiomics levels. The optimal subtypes interpret the metabolic characteristics of PVTT formation and development. The combined index provided effective predictions of prognosis and immunotherapy responses. Patients with a higher combined index had a relatively poor prognosis (p <0.001). We also found metabolism of polyamines was a key metabolic pathway involved in conversion of metabolic heterogeneity in HCC and PVTT, and identified ODC1 was significantly higher expressed in PVTT compared to normal tissue (p =0.03). Our findings revealed both consistency and heterogeneity in the metabolism of non-malignant cells in HCC and PVTT. The risk stratification based on cancer-associated fibroblasts and myeloid cells conduce to predict prognosis and guide treatment. This offers new directions for understanding disease development and immunotherapy responses., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Purpose: To assess the efficacy of electronic health record (EHR) messaging for re-engaging patients with ophthalmology care after a missed appointment., Design: Prospective, randomized clinical trial., Methods: The study setting was an academic ophthalmology department. The patient population comprised of return patients age 18 years or older with an appointment "no show," or missed appointment. Over 2 phases of recruitment, 362 patients with an active patient portal in the EHR were selected consecutively each business day. Patients were randomized using a web-based tool to receive a reminder to reschedule via a standard mailed letter only (control) or the mailed letter plus an electronic message through the EHR within 1 business day of the missed appointment (intervention). Reengagement with eye care was defined as attendance of a rescheduled appointment within 30 days of the no-show visit. Patient charts were reviewed for demographic and clinical data., Results: The average age of recruited patients was 59.9 years, just under half of the sample was male (42.5%, 154/362), and most patients were White (56.9%, 206/362) or Black (36.2%, 131/362). Patients were most commonly recruited from the retina service (39.2%, 142/362) followed by the glaucoma service (29.3%, 106/362). Many patients in this study had previous no-show appointments, with an average no-show rate of 18.8% out of all scheduled visits across our health system. In total, 22.2% (42/189) of patients in the intervention group attended a follow-up appointment within 30 days of their no-show visit compared to 11.6% (20/173) of the control group (OR, 2.186; 95% CI, 1.225-3.898; P = .008). When including only the 74 patients in the intervention group who read the intervention message in the patient portal, 28.4% (21/74) attended a follow-up compared to 11.6% (20/173) of the control group (P = .001)., Conclusions: EHR-based reminder messages sent within a business day of a missed appointment may promote re-engagement in ophthalmology care after appointment no-show., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI) < 0.5 and 25 IVF cycles with FOI ≥ 0.5 were included in this study. Baseline demographic characteristics were compared between the two groups. Metagenomic sequencing was performed to analyze fecal microbial community profiles. Mice were used to evaluate the effect of Bifidobacterium&#95;longum on ovarian response to stimulation. Compared with FOI < 0.5 group, women in group with FOI ≥ 0.5 had significant more oocytes retrieved (p < 0.01). Prevotella&#95;copri, Bateroides&#95;vulgatus, Escherichia&#95;coli and Bateroides&#95;stercoris were more abundant in FOI < 0.5 group while Bifidobacterium&#95;longum, Faecalibacterium&#95;prausnitzii, Ruminococcus&#95;gnavus and Bifidobacterium&#95;pseudocatenula were more abundant in FOI ≥ 0.5 group. After adjusting for women's age and BMI, Pearson correlation analysis indicated alteration of gut microbiome was related with serum E2, FSH, number of oocytes retrieved and clinical pregnancy rate. Animal study showed ovarian response will be improved after Bifidobacterium&#95;longum applied. An increased abundance of Bacteroidetes and Prevotella copri, as well as a decreased abundance of Bifidobacterium longum, have been found to be associated with poor ovarian responsiveness. Changes in gut microbiomes have been observed to be correlated with certain clinical characteristics. The potential enhancement of ovarian response may be facilitated by the integration of Bifidobacterium longum., (© 2024. The Author(s).)

Mammalian kidneys are responsible for removing metabolic waste and maintaining fluid and electrolyte homeostasis via selective filtration. One of the proteins closely linked to selective renal filtration is myosin 1e (Myo1e), an actin-dependent molecular motor found in the specialized kidney epithelial cells involved in the assembly and maintenance of the renal filter. Point mutations in the gene encoding Myo1e, MYO1E, have been linked to familial kidney disease, and Myo1e knockout in mice leads to the disruption of selective filtration. In this review, we discuss the role of the actin cytoskeleton in renal filtration, the known and hypothesized functions of Myo1e, and the possible explanations for the impact of MYO1E mutations on renal function., (© 2024 Wiley Periodicals LLC.)

In recent years, with sinomenine hydrochloride as the main ingredient, Qingfengteng had been formulated as various dosage forms for clinical treatment. Subsequent findings confirmed a variety of biological roles for sinomenine. Here, 15 H 2 S-donating sinomenine derivatives were synthesized. Target hybrids a11 displayed substantial cytotoxic effects on cancer cell lines, particularly against K562 cells, with an IC 50 value of 1.36 μM. In-depth studies demonstrated that a11 arrested cell cycle at G1 phase, induced apoptosis via both morphological changes in nucleus and membrane potential collapse in mitochondria. These results indicated a11 exerted an antiproliferative effect through apoptosis induction via mitochondrial pathway.

CD4 + CD25 + regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4 + CD25 high CD127 low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 10 4 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS., (© 2024. The Author(s).)

Background: In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The β-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells., Methods: Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of β-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.)., Results: Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and β-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of β-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam-all of which are targets within the Wnt/β-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with β-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation., Conclusion: Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the β-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The optimal dietary regimen for polycystic ovary syndrome (PCOS) has not been identified. High-protein diets (HPDs) are effective for weight control in individuals with metabolic abnormalities, but no systematic meta-analyses have yet summarised the effects of HPDs on PCOS. Seven electronic databases were searched from inception to 30 April 2023, and studies comparing the effects of HPDs and other diets on the anthropometrics, metabolic factors, and hormonal profiles for PCOS were identified. Data were pooled using random-effects models and expressed as weighted mean differences and 95% confidence intervals. The risk of bias was assessed by Cochrane Collaboration tool. Eight trials involving 300 women with PCOS were included. Compared with isocaloric balanced diets (BDs), HPDs significantly reduced fasting insulin (-2.69 μIU/mL, 95% CI [-3.81, -1.57], P < 0.0001, I 2  = 46%) and homoeostatic model assessment for insulin resistance (HOMA-IR-0.41, 95% CI [-0.80, -0.02], P = 0.04, I 2  = 94%) in women with PCOS. However, HPDs and BDs had comparable effects on weight loss, abdominal adiposity, lipid profiles, and reproductive hormones (all P ≥ 0.05). HPDs may benefit women with PCOS in terms of improving insulin resistance, supporting for their use as one of the dietary management options for PCOS, however further RCTs in larger and broader settings are required to confirm these observations and investigate the mechanism behind it., (© 2024. The Author(s).)

Objective: To investigate the effects of Ziyin Liangxue formula combined with prednisone on immune function and the ST2/IL-33 pathway in mice with immune thrombocytopenia., Methods: In 40 BALB/c mice, 32 were constructed as immune thrombocytopenia mouse models by antiplatelet serum injection. After successful modeling, the mice were randomly divided into model group, Ziyin Liangxue formula group (0.2 ml/10 g), prednisone group (0.2 ml/10 g), and Ziyin Liangxue formula + prednisone group (0.2 ml/10 g), 8 mice in each group, and the other 8 mice were set as control group. The drugs were administered by gavage at the dose, and the model group and control group were given equal amounts of saline by gavage once a day for 2 weeks of continuous intervention. Blood samples and spleen tissues were collected, the peripheral platelet count was measured by automatic hematology analyzer, the pathological changes in spleen tissue was observed by HE staining, the levels of serum transforming growth factor (TGF)-β, interleukin (IL)-17, and peripheral blood thrombopoietin (TPO) were detected by enzyme-linked immunosorbent assay (ELISA), the expression of IL-33, sST2, and ST2 in spleen tissue was detected by Western blot, and the cell counts of peripheral blood Th17 and Treg were detected by flow cytometry., Results: Compared with the control group, the number of platelets, the level of TPO, TGF-β, and Treg cells were significantly decreased ( P <0.05), while the level of IL-17, Th17 cells, and the expression of IL-33, sST2, and ST2 protein were significantly increased in the model group ( P <0.01). Compared with the model group, the number of platelets, the level of TPO, TGF-β, and Treg cells were significantly increased ( P <0.05), while the level of IL-17, Th17 cells, and the expression of IL-33, sST2, and ST2 protein were significantly decreased in the Ziyin Liangxue formula + prednisone group ( P <0.01)., Conclusion: Ziyin Liangxue formula + prednisone can effectively regulate Th17/Treg balance, thus effectively improve immune thrombocytopenia, and the mechanism may be related to the regulation of ST2/IL-33 signaling pathway.

Purpose: To assess the incidence, risk factors, and clinical consequences of loss to follow up (LTFU) among glaucoma patients at our institution over a 10-year period., Methods: This retrospective study examined LTFU among a cohort of glaucoma patients with a clinical encounter in 2010. LTFU was defined as 52 weeks or more without an encounter and without alternative reason for discontinued care, such as discharge, documented move, or death. Baseline demographic and clinical characteristics were collected and compared between LTFU and non-LTFU groups using a logistic regression model to identify risk factors for LTFU. Odds ratios (ORs) are reported with 95% confidence intervals. Clinical outcomes were documented for LTFU patients who returned after a lapse in care., Results: Among the 395 included patients, 132 (33%) were LTFU over the 10-year study period. Characteristics associated with LTFU in a logistic regression model included greater disease severity (OR = 1.03 [1.01-1.05], p = .023, for each worsening decibel of mean deviation) and in-state rather than out-of-state residence (OR = 2.76 [1.12-6.80], p = .027). Other potential risk factors that did not reach significance included male gender (OR = 1.39 [0.92-2.13], p = .124), Black race (OR = 1.40 [0.91-2.16] p = .123), and legal blindness (OR = 1.58 [0.91-2.76] p = .107). Among the 132 patients who were LTFU, only 23 (17%) later returned to care, two-thirds (15/23) of whom returned with disease progression or complication., Conclusion: One-third of glaucoma patients became LTFU over a 10-year period, and LTFU may be associated with poor clinical outcomes. More research is needed to understand reasons for LTFU and to promote regular glaucoma care.

The theft of controlled substances has been studied in the community and healthcare settings including hospitals, pharmacies, hospice, and pain clinics. However, research on these thefts in long-term care homes has yet to be published. This exploratory study makes first steps toward bridging this gap. Using 107 Minnesota Department of Health's investigation reports substantiated as "drug diversion" between 2013 and 2021 in assisted living residences and nursing homes, we found that 11,328.5 tablets were stolen from 368 residents (97.5% were controlled substances), with over 30 tablets stolen per resident. We also identified the types of medications stolen, duration of theft, extent to which nurses stole the medications or were those initially suspecting thefts, and the role of surveillance cameras in confirming allegations. The findings could raise awareness to this form of elder mistreatment in long-term care homes and call for action to address it.

Global reef degradation is a critical environmental health issue that has triggered intensive research on ocean warming, but the implications of emerging contaminants in coral habitats are largely overlooked. Laboratory experiments assessing organic ultraviolet (UV) filter exposure have shown that these chemicals negatively affect coral health; their ubiquitous occurrence in association with ocean warming may pose great challenges to coral health. We investigated both short- (10-day) and long-term (60-day) single and co-exposures of coral nubbins to environmentally relevant organic UV filter mixtures (200 ng/L of 12 compounds) and elevated water temperatures (30 °C) to investigate their effects and potential mechanisms of action. The initial 10-day exposure of Seriatopora caliendrum resulted in bleaching only under co-exposure conditions (compounds + temperature). The 60-day mesocosm study entailed the same exposure settings with nubbins of three species (S. caliendrum, Pocillopora acuta and Montipora aequituberculata). Bleaching (37.5 %) and mortality (12.5 %) of S. caliendrum were observed under UV filter mixture exposure. In the co-exposure treatment, 100 % S. caliendrum and P. acuta bleached associating with 100 % and 50 % mortality, respectively, and significant increase of catalase activities in P. acuta and M. aequituberculata nubbins were found. Biochemical and molecular analyses indicated significant alteration of oxidative stress and metabolic enzymes. The results suggest that upon the adverse effects of thermal stress, organic UV filter mixture at environmental concentrations can cause bleaching in corals by inducing a significant oxidative stress and detoxification burden, suggesting that emerging contaminants may play a unique role in global reef degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Patients on hemodialysis (HD) or peritoneal dialysis (PD) often have insufficient energy and protein intake, resulting in poor nutritional status and adverse outcomes. Oral nutritional supplements (ONSs) are the most commonly used to increase such patients' energy and protein intakes., Methods: In this systematic review and meta-analysis, we analyzed studies on nutritional status, inflammatory markers, and electrolyte levels in patients on dialysis receiving ONSs. We searched four electronic databases from inception until 31 December 2022, for randomized controlled trials comparing ONS treatment versus placebo or routine care., Results: 22 studies with 1185 patients on dialysis were included in our meta-analysis. Compared with the control group, the ONS group exhibited significantly increased serum albumin levels [1.26 g/l (95%CI, 0.50-2.02, P  < 0.0001; I 2  = 80.4%)], body mass indexes (BMIs) [0.30 kg/m 2 (95%CI, 0.09-0.52, P  = 0.005; I 2  = 41.4%)], and handgrip strength (HGS) [0.96 kg (95%CI, 0.07-1.84, P  = 0.034; I 2  = 41.4%)] from baseline to the end of intervention. No significant differences were observed between the groups in lean body mass, phase angle, C-reactive protein, and serum phosphorus and potassium levels. In terms of improving albumin, the subgroup analyses show that ONS use seems to be more inclined to three variations: HD patients, short-term use, and non-intradialytic supplementation., Conclusion: In conclusion, ONS use can improve the nutritional status of patients on dialysis in terms of their serum albumin, BMI, and HGS without significant effects on serum phosphorus, potassium, and C-reactive protein levels. However, it remains uncertain whether these results translate to improvement in clinically relevant outcomes. Large-scale high-quality studies are still required in this population., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Increasing evidence indicates the importance of CD8 + T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8 + memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity., Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8 + memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS., Results: We found that MS patients had elevated frequency of MOG-specific CD8 + T cells, MOG-specific central memory T cells (T CM ), MOG-specific CD8 + effector memory T cells (T EM ), and MOG-specific CD8 + terminally differentiated cells (T EMRA ); elevated granzyme B expression on MOG-specific CD8 + T CM ; and, on MOG-specific CD8 + T EM , elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8 + T CM , granzyme B expression in CD8 + T CM , and granzyme B and perforin expression on CD8 + T EM , but with reduced PD-1 expression on CD8 + T EM ., Conclusion: The dysregulation of antigen-specific CD8 + memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Yang, Fan, Yuan, Ma, Wang, Lu, Yuan, Zou, Zhang and Liu.)

Background: As a highly prevalent malignancy among women worldwide, breast cancer, remains a critical public health issue necessitating the development of novel therapeutics and biomarkers. Kruppel Like Factor 2 (KLF2), a member of the Kruppel family of transcription factors, has been implicated in various types of cancer due to its diminished expression; however, the potential implications of KLF2 expression in relation to breast cancer progression, prognosis, and therapy remain unclear. Methods: The present study employed the Tumor Immune Estimation Resource (TIMER) and The Human Protein Atlas databases to investigate the expression pattern of KLF2 in pan-cancer. The relationship between KLF2 expression and clinical features or immune infiltration of The Cancer Genome Atlas (TCGA) breast cancer samples was evaluated using Breast Cancer Integrative Platform (BCIP) and TIMER. The expression levels of KLF2 in breast cancer were validated via immunohistochemical staining analysis. Gene Set Enrichment Analysis (GSEA) to study the KLF2-related gene ontology. STRING database was employed to construct a protein-protein interaction (PPI) network of KLF2 in relation to vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1α (HIF1α). The expression of KLF2 following diverse breast cancer therapies was analyzed in the Gene Expression Omnibus (GEO) databases. The expression of KLF2 following treatment with simvastatin was validated via immunofluorescence and western blotting. Results: Our study reveals that KLF2 displays significantly reduced expression in cancerous tissues compared to non-cancerous controls. Patients with low KLF2 expression levels exhibited poor prognosis across multiple cancer types. KLF2 expression levels were found to be reduced in advanced cancer stages and grades, while positively correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and tumor size in breast cancer. KLF2 expression is associated with diverse immune infiltration cells, and may impact the breast tumor immune microenvironment by regulating dendritic cell activation. Additionally, we observed a negative correlation between KLF2 expression levels and angiogenesis, as well as the expression of VEGFA and HIF1α. Notably, the anticancer drug simvastatin could induce KLF2 expression in both breast cancer. Conclusion: Based on our observations, KLF2 has potential as a diagnostic, prognostic, and therapeutic biomarker for breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor, YZ, declared a shared parent affiliation with the authors Y-ZL, R-QW, Y-QG, P-JL, and JL at the time of review., (Copyright © 2023 Li, Xie, Wang, Gao, Liu and Liu.)

Cancer is a leading cause of mortality worldwide. Over 50% of cancers are diagnosed late, rendering many treatments ineffective. Existing liquid biopsy studies demonstrate a minimally invasive and inexpensive approach for disease detection but lack parsimonious biomarker selection, exhibit poor cancer detection performance and lack appropriate validation and testing. We established a tailored machine learning pipeline, DEcancer, for liquid biopsy analysis that addresses these limitations and improved performance. In a test set from a published cohort of 1,005 patients including 8 cancer types and 812 cancer-free individuals, DEcancer increased stage 1 cancer detection sensitivity across cancer types from 48 to 90%. In addition, with a test set cohort of patients from a high dimensional proteomics dataset of 61 lung cancer patients and 80 cancer-free individuals, DEcancer's performance using a 14-43 protein panel was comparable to 1,000 original proteins. DEcancer is a promising tool which may facilitate improved cancer detection and management., Competing Interests: A.H. is a founder, an employee, and shareholder of Oxford Cancer Analytics Ltd. L.H. is an employee of Oxford Cancer Analytics Ltd. Z.L. is an employee of Oxford Cancer Analytics Ltd. F.P. was an employee and is a shareholder of Oxford Cancer Analytics Ltd. D.S. is an employee and shareholder of Oxford Cancer Analytics Ltd. E.M. is an employee of Oxford Cancer Analytics Ltd. G.L. declares no competing interests. B.K. is a shareholder and member of the Scientific Advisory Board of Oxford Cancer Analytics Ltd. J.S. is an employee of Oxford Cancer Analytics Ltd. P.J.L. is a founder, an employee and shareholder of Oxford Cancer Analytics Ltd. A.H. and P.J.L. are co-inventors of the patent “A METHOD AND SYSTEM DETECTING A HEALTH ABNORMALITY IN A LIQUID BIOPSY SAMPLE” (International Patent Application Number: PCT/EP2022/075710)., (© 2023 The Authors.)

People are fundamentally social beings and enjoy connecting with others. Sometimes, people reach out to others-whether simply to check-in on how others are doing with brief messages or to show that they are thinking of others by sending small gifts to them. Yet, despite the importance and enjoyment of social connection, do people accurately understand how much other people value being reached out to by someone in their social circle? Across a series of preregistered experiments, we document a robust underestimation of how much other people appreciate being reached out to. We find evidence compatible with an account wherein one reason this underestimation of appreciation occurs is because responders (vs. initiators) are more focused on their feelings of surprise at being reached out to. A focus on feelings of surprise in turn predicts greater appreciation. We further identify process-consistent moderators of the underestimation of reach-out appreciation, finding that it is magnified when the reach-out context is more surprising: when it occurs within a surprising (vs. unsurprising) context for the recipient and when it occurs between more socially distant (vs. socially close) others. Altogether, this research thus identifies when and why we underestimate how much other people appreciate us reaching out to them, implicating a heightened focus on feelings of surprise as one underlying explanation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective: To analyze the factors influencing the distribution of 131-I in the liver of patients with advanced hepatic carcinoma treated with the combination of Licartin ( 131 I Metuximab) and transcatheter arterial chemoembolization (TACE). This study provides a reference and basis for the clinic on how to choose the best time for the treatment of Licartin and how to reduce other possible factors affecting the role of Licartin., Methods: Data from 41 patients with advanced hepatic carcinoma treated with the combination of Licartin and TACE in the Interventional Department of our hospital from March 2014 to December 2020 were collected. This included general characteristics, history of open and interventional surgery, interval between the last interventional surgery and the Licartin treatment, selected arteries in the Licartin perfusion, and 131-I distribution in the liver. Regression analysis was conducted to investigate the factors affecting the distribution of 131 I in the liver., Results: In 14 cases (34.1%), 131-I was evenly distributed in the liver, and there was no correlation between the cause of even distribution with age(OR=0.961, P = 0.939), previous open surgery history(OR=3.547,P= 0.128), previous history of interventional therapy(OR=0.140,P = 0.072), the interval between the last interventional surgery and the Licartin treatment(OR=0.858,P = 0.883), or the choice of the perfusion artery in the Licartin treatment (OR=1.489,P = 0.419). In 14 cases (34.1%), there was higher aggregation in the tumor than in the normal liver, which was related to previous interventional surgery (OR=7.443,P = 0.043). In 13 cases (31.7%), there was lower aggregation in the tumor than in the normal liver, which was related to the selected vessels in the Licartin perfusion (OR=0.23,P = 0.013)., Conclusion: The effective aggregation of 131-I in the liver, even in tumors, the previous history of TACE, and the choice of vessels in the Licartin infusion might be the factors influencing the distribution of 131-I in the liver during hepatic artery infusion of Licartin in combination with TACE therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Li, Li, Lv, Chen, Zhu and Liu.)

The neurotrophin brain-derived neurotrophic factor (BDNF), which acts as a transducer, is responsible for improving cerebral stroke, neuropathic pain, and depression. Exercise can alter extracellular nucleotide levels and purinergic receptors in central nervous system (CNS) structures. This inevitably activates or inhibits the expression of BDNF via purinergic receptors, particularly the P2X receptor (P2XR), to alleviate pathological progression. In addition, the significant involvement of sensitive P2X4R in mediating increased BDNF and p38-MAPK for intracerebral hemorrhage and pain hypersensitivity has been reported. Moreover, archetypal P2X7R blockade induces mouse antidepressant-like behavior and analgesia by BDNF release. This review summarizes BDNF-mediated neural effects via purinergic receptors, speculates that P2X4R and P2X7R could be priming molecules in exercise-mediated changes in BDNF, and provides strategies for the protective mechanism of exercise in neurogenic disease., (© 2022. The Author(s).)

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer (CRC). In this study, we identified reduced microvessel density (MVD) and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance. We focused on the effect of metformin on MVD, vascular maturity, and endothelial apoptosis of CRCs with a non-angiogenic phenotype, and further investigated its effect in overcoming chemoresistance. In situ transplanted cancer models were established to compare MVD, endothelial apoptosis and vascular maturity, and function in tumors from metformin- and vehicle-treated mice. An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis. Transcriptome sequencing was performed for genetic screening. Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage, immaturity, reduced MVD, and non-hypoxia. This phenomenon had also been observed in human CRC. Furthermore, non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro. By suppressing endothelial apoptosis, metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity. Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling, which was abrogated by metformin administration. These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC. By suppressing endothelial apoptosis, metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

Osteoarthritis (OA) is a degenerative disease that occurs mostly in the elderly, and its specific pathogenesis is still unknown, but recent studies have found that circular RNA generally display aberrant expression in OA. Our study explored the expression characteristics and mechanism of action of circ-NT5C2 in OA. Circ-NT5C2, microRNA-142-5p (miR-142-5p), and nicotinamide phosphoribosyltransferase (NAMPT) mRNA levels were measured using RT-qPCR. Western blot was employed to assess the protein level of NAMPT and extracellular matrix (ECM) production-related markers. The viability, proliferation, apoptosis and inflammation were examined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Relationship between miR-142-5p and circ-NT5C2 or NAMPT was demonstrated by dual-luciferase reporter system and RNA immunoprecipitation assay. We reported that circ-NT5C2 and NAMPT were greatly upregulated, and miR-142-5p level was constrained in OA tissues and in a cell model. Circ-NT5C2 silencing alleviated IL-1β-induced inhibitory effects on chondrocyte proliferation and ECM generation, meanwhile the promotional role of IL-1β on chondrocyte apoptosis and inflammation was also weakened. The targeting relationship of miR-142-5p with either circ-NT5C2 or NAMPT was confirmed. Knockdown of miR-142-5p reversed the suppressive effects of circ-NT5C2 silencing on the OA progression in vitro, and NAMPT overexpression also attenuated the effects of miR-142-5p upregulation in an OA cell model. Collectively, circ-NT5C2 accelerated the OA process by targeting the miR-142-5p/NAMPT axis. This study provides valuable information to find a better treatment for OA., (© 2022 The Societies and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P <0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P <0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E ( P =0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P <0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

In this study, we collected plant material from Pseudotsuga sinensis in Guizhou, China, and sequenced it. The complete chloroplast genome consisted of 122,243 bp, including a large single-copy (LSC) region, a small single-copy (SSC) region, and two inverted repeat regions like those in P. sinensis var. wilsoniana . The GC content of P. sinensis and P. sinensis var. wilsoniana are 38.7% and 38.8%, respectively. The reconstructed phylogenetic tree reveals that P. sinensis was a sister species to P. sinensis var. wilsoniana . Hence, the availability of the chloroplast genome of P. sinensis will promote further phylogenetic studies of the family Pinaceae., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Sarcopaenia is an age-related disease affected by many factors, nutrition being one. Reduced protein intake and decreased diet quality are correlated with sarcopaenia. Protein, amino acid, or peptide supplementation is a commonly used clinical practice to increase protein intake. However, whether supplementation plays a key role in preventing and treating sarcopaenia and whether it needs to be combined with other interventions is worthy of study. This review focuses on protein, amino acid, and peptide supplementation for the prevention and treatment of sarcopaenia.

Using a mix-method design, we examined participants' willingness to respond to mass marketing scams (MMS). In Experiment 1, we examined the effect of age (young versus older) and letter style ("hot" versus "cold") on the intention to respond. The intention of responding was negatively associated with risk ( p  < .001) and having at least a high school education was positively associated with perception of benefits (b = .684, p  < .001). In Experiment 2, we examined reward sensitivity on the intention to respond by manipulating reward amounts (low versus high) and the presence of an activation fee. The presence of an activation fee decreased intent to contact, but percentages remained high (25.75%). Analyses of qualitative data indicated that risk and benefit were both predicted by perceived self-efficacy. The results indicate that consumers' beliefs about their ability to control the outcomes of future interactions affected how they behaved when provided with MMS materials.

Introduction: Social determinants of health can limit access to regular eye care, but their role in ophthalmology is underexamined. The purpose of this study is to assess the relationship between patient characteristics and self-reported barriers to eye care., Methods: This anonymous, cross-sectional survey was conducted at a 2-day free eye clinic event in Pittsburgh, Pennsylvania. Adult patients presenting for vision screening were eligible to participate. Patient characteristics (demographics, health status) and self-reported barriers to eye care were collected. Predictors of barriers to eye care were analyzed using binary logistic regression., Results: Of 269 eligible, consecutive patients approached for survey completion, 183 comprised the volunteer sample. The 183 participants (105 female patients [59%]) had a mean (standard deviation) age of 53 (15) years and generally self-identified as Black (74, 46%) or White (67, 41%). While a third reported having no health insurance (60, 34%), the remaining two-thirds of participants had public (84, 48%) or private coverage (34, 19%). Three-quarters of respondents reported at least one barrier to receiving regular eye care (136, 76%), most commonly medical costs (89, 50%) and insurance issues (73, 41%). Not having health insurance or vision insurance was strongly associated with reporting at least one barrier to care (OR: 5.00, p = 0.002, and OR: 7.46, p < 0.001, respectively). Those with self-reported eye disease were more likely to report transportation difficulties (OR: 4.45, p = 0.013), and employed participants reported difficulty getting time off work to attend eye exams (OR: 7.73, p = 0.002). Finally, compared to Black race, White race was associated with a higher likelihood of reporting any barrier to care (OR: 2.79, p = 0.013)., Conclusion: Three-quarters of vision screening attendees reported at least one barrier to regular eye care, most commonly medical costs and insurance., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

In the past decade, the frequency of mass coral bleaching events has increased due to seawater temperature anomalies persisting for longer periods. Coral survival from temperature anomalies has been based on how each species in each location responds to stress, which is unique to individual species and may be due to the way stressful experiences accumulate through time in the form of ecological and physiological memory. A deeper understanding of ecological and physiological memory in corals is necessary to understand their survival strategies into the future. Laboratory experiments can help us simulate seawater temperatures experienced by corals in the past and compare their responses to those of the present and future. In this study, we sampled corals with different life history traits from one location perturbed by seawater temperature incursions (variable site) and from a second, relatively undisturbed location (stable site). We sampled across two seasons to observe the responses to bleaching threshold temperatures in the past (1998-29 °C), present (2018-31 °C), and future (2050-33 °C). Corals were healthy at 29 °C and 31 °C, but a fast-growing, temperature-susceptible coral species experienced high mortality at 33 °C compared to a slow-growing, temperature-resistant coral species. Moreover, corals from the variable site and during the spring season fared better under temperature stress. The results of this study provide insight into the possible role of life-history traits on coral's response to seasons and locations in terms of memory to long-term and short-term thermal anomalies and climate change., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study aimed to explore risk factors, clinical features, and prognosis of patients with hypertrophic cardiomyopathy (HCM) complicated by ischemic stroke (IS)., Methods: We conducted a retrospective analysis of all HCM patient data and a 1-year follow-up study., Results: Totally, 506 patients with HCM, including 71 with IS, were enrolled. Older age (≥63 years) was associated with an increased risk of IS in HCM patients (OR = 1.045, 95% CI: 1.018-1.072, p = 0.001). Among 37 patients complicated by IS, 22 (59.5%, 22/37) manifested as cardioembolism (CE) subtype, and 13 (35.1%, 3/37) small artery occlusion (SAO) subtype, according to TOAST classification. In the acute phase, the IS patients presented with NIHSS 4 (interquartile range: 1, 10). Multi-infarction was more common than single infarction (72.7 vs. 27.3%), while cortical + subcortical infarction (CE group: 50%) or subcortical infarction (SAO group: 53.8%) constituted most IS cases. Additionally, the blood supply areas of anterior circulation (CE group: 45.5%; SAO group: 92.3%) or anterior + posterior circulation (CE group: 50%) were mainly involved. The 1-year survival rate of HCM patients with concomitant IS was 81.8%, and IS was associated with 1-year all-cause death in HCM patients (HR = 5.689, 95% CI: 1.784-18.144, p = 0.003)., Conclusion: Older age is a risk factor for IS occurrence in HCM patients. Patients with HCM complicated by IS had mild or moderate neurologic deficits at disease onset. CE and SAO subtypes predominate in patients with concomitant IS, especially the former. Multiple cortical and subcortical infarctions are their neuroimaging characteristics, mainly involving the anterior circulation or anterior + posterior circulation. Is is a risk factor for all-cause death in HCM patients within 1 year., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Fan, Li, Wang, Ma, Yuan, Yang, Liu and Liu.)

Objective: To observe the effect of electroacupuncture (EA) on the pyrolysis of dopaminergic neurons in rats with Parkinson's disease (PD), so as to explore its underlying molecular mechanism., Methods: Male SD rats were randomly divided into the sham operation, model, EA, MCC950 and EA+MCC950 groups, with 12 rats in each group. The PD rat model was established by two-point injection of 6-OHDA. Rats in the MCC950 group were injected with MCC950 at the dose of 10 mg/kg, once a day; for rats of EA group, EA was applied to "Taichong" (LR3) and "Fengfu"(GV16) for 30 min, once a day; rats in the EA+ MCC950 group were given MCC950 injection and EA once a day. All above interventions were performed for 2 weeks. After the intervention, the behavioral changes of rats were observed using rotating induction experiment, rotating rod experiment and open field experiment; the positive expressions of dopaminergic neuronal markers tyrosine hydroxylase (TH) and α-Synuclein (α-Syn) in substantia nigra striatum were detected by immunohistochemistry; the damage of dopaminergic neurons in substantia nigra striatum was observed after HE staining; immunopositive coexpression of brain nucleotide-binding oligomerization domain like receptor protein 3 (NLRP3), Caspase-1 and ionized calcium binding adapter1 (Iba-1) were detected by immunofluorescence double staining; the levels of interleukin (IL)-1β and IL-18 in brain tissues were detected by ELISA; the protein expression levels of NLRP3, Cleaved Caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) in the substantia nigra striatum were detected by Western blot., Results: Compared with the sham operation group, the number of rotations of rotating induction experiment, the residence time in the central area of open field experiment, the positive expression of α-Syn, the positive co-expressions of NLRP3/Iba-1 and Caspase-1/Iba-1, the contents of IL-1β and IL-18 in brain tissues, and the protein expression levels of NLRP3, ASC and Cleaved Caspase-1 in substantia nigra striatum were significantly increased ( P <0.05), while the drop latency of rotating rod experiment, the rearing times and the total distance of open field experiment, and the positive expression of TH in substantia nigra striatum were significantly decreased ( P <0.05) in the model group. Compared with the model group, the above mentioned markers were reversed in EA, MCC950 and EA+MCC950 groups ( P <0.05), and the improvement of the EA+MCC950 group was more obvious than those of the MCC950 and EA groups. In the model group, the neurons were disorderly arranged, the number of neurons was reduced, the cytoplasm was swollen, and some of them were vacuolar degeneration; while the degree of neuronal arrangement disorder, cytoplasmic swelling and the vacuolar degeneration were reduced in varying degrees in the MCC950, EA and EA+MCC950 groups., Conclusion: The ameliorative effect of EA on dopaminergic neuron damage in PD rats may be related to its effects in inhibiting NLRP3/Caspase-1 mediated neuronal pyrosis.

Background: Myo1e is a nonmuscle motor protein enriched in podocytes. Mutations in MYO1E are associated with steroid-resistant nephrotic syndrome (SRNS). Most of the MYO1E variants identified by genomic sequencing have not been functionally characterized. Here, we set out to analyze two mutations in the Myo1e motor domain, T119I and D388H, which were selected on the basis of protein sequence conservation., Methods: EGFP-tagged human Myo1e constructs were delivered into the Myo1e-KO mouse podocyte-derived cells via adenoviral infection to analyze Myo1e protein stability, Myo1e localization, and clathrin-dependent endocytosis, which is known to involve Myo1e activity. Furthermore, truncated Myo1e constructs were expressed using the baculovirus expression system and used to measure Myo1e ATPase and motor activity in vitro ., Results: Both mutants were expressed as full-length proteins in the Myo1e-KO cells. However, unlike wild-type (WT) Myo1e, the T119I variant was not enriched at the cell junctions or clathrin-coated vesicles (CCVs). In contrast, D388H variant localization was similar to that of WT. The rate of dissociation of the D388H variant from cell-cell junctions and CCVs was decreased, suggesting this mutation affects Myo1e interactions with binding partners. ATPase activity and ability to translocate actin filaments were drastically reduced for the D388H mutant, supporting findings from cell-based experiments., Conclusions: T119I and D388H mutations are deleterious to Myo1e functions. The experimental approaches used in this study can be applied to future characterization of novel MYO1E variants associated with SRNS., (Copyright © 2022 by the American Society of Nephrology.)

Background and Objectives: Adult Protective Services (APS) are the frontline agencies investigating elder mistreatment and providing/coordinating postinvestigation services. Yet, their effectiveness in reducing different types of mistreatment in relation to services is unknown. This study aimed to address the knowledge gap by identifying services provided by mistreatment type, and examining the associations of services with mistreatment reduction., Research Design and Methods: A pretest-post-test design was implemented using the Identification, Services, and Outcomes (ISO) Matrix to assess mistreatment levels during case investigation and at case closure after services were provided. San Francisco and Napa APS participated in a 6-month data collection., Results: The 4 most prevalent types of mistreatment were examined: emotional, physical, financial abuse, and neglect by others. On average, level of mistreatment decreased across mistreatment types after APS intervention. Care/case management, mental health, and other services were most common, while specific services differed depending on type of mistreatment. Care/case management services were associated with physical and emotional abuse reduction, legal services further correlated with emotional abuse reduction; financial planning services were associated with financial abuse reduction; care/case management and other services were associated with neglect reduction., Discussion and Implications: This is the first study to address APS services by mistreatment type and the outcomes of services. Adoption of the ISO Matrix by APS programs opens the possibility of research and practice collaboration in APS outcomes research using a standardized approach., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.)