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We examined the mechanism by which lithium chloride (LiCl) attenuates the impaired learning capability and memory function of dual‐transgenic APP/PS1 mice. Six‐ or 12‐month‐old APP/PS1 and wild‐type (WT) mice were randomized into four groups, namely WT, WT+Li (100 mg LiCl/kg body weight, gavage once daily), APP/PS1 and APP/PS1+Li. Primary rat hippocampal neurons were exposed to β‐amyloid peptide oligomers (AβOs), LiCl and/or XAV939 (inhibitor of Wnt/β‐catenin) or transfected with small interfering RNA against the β‐catenin gene. In the cerebral zone of APP/PS1 mice, the level of Aβ was increased and those of α7 nicotinic acetylcholine receptors (nAChR), phosphor‐GSK3β (ser9), β‐catenin and cyclin D1 (protein and/or mRNA levels) reduced. Two‐month treatment with LiCl at ages of 4 or 10 months weakened all of these effects. Similar expression variations were observed for these proteins in primary neurons exposed to AβOs, and these effects were attenuated by LiCl and aggravated by XAV939. Inhibition of β‐catenin expression lowered the level of α7 nAChR protein in these cells. LiCl attenuates the impaired learning capability and memory function of APP/PS1 mice via a mechanism that might involve elevation of the level of α7 nAChR as a result of altered Wnt/β‐catenin signalling.

Introduction The lack of an effective continuing professional development programme for qualified surgeons, specifically one that enhances non-technical skills (NTS), is an issue receiving increased attention. Peer-based coaching, used in multiple professions, is a proposed method to deliver this. The aim of this study was to undertake a systematic review of the literature to summarize the quantity and quality of studies involving surgical coaching of NTS in qualified surgeons. Methods A systematic search of the literature was performed through MEDLINE, EMBASE, Cochrane Collaboration and PsychINFO. Studies were selected based on predefined inclusion and exclusion criteria. Data for the included studies was independently extracted by two reviewers and the quality of the studies evaluated using the Medical Education and Research Study Quality Instrument (MERSQI). Results Some 4319 articles were screened from which 19 met the inclusion criteria. Ten studies involved coaching of individual surgeons and nine looked at group coaching of surgeons as part of a team. Group coaching studies used non-surgeons as coaches, included objective assessment of NTS, and were of a higher quality (average MERSQI 13.58). Individual coaching studies focused on learner perception, used experienced surgeons as coaches and were of a lower quality (average MERSQI 11.58). Individual coaching did not show an objective improvement in NTS for qualified surgeons in any study. Conclusion Surgical coaching of qualified surgeons’ NTS in a group setting was found to be effective. Coaching of individual surgeons revealed an overall positive learner perception but did not show an objective improvement in NTS for qualified surgeons.

Background Surgical outpatient consultations are demanding for the surgeon and patients without a definite formula for success. Various factors have been identified regarding factors that influence patient satisfaction and engagement. We aimed to examine the modern-day surgical outpatient consultation and report on these factors. Methods An observational cross-sectional study was performed by reviewing video recordings of 182 surgical consultations by 12 surgeons at The Queen Elizabeth Hospital, South Australia, Australia. Results The mean consultation time was 12.3 min, with pre-surgical consultations being the longest. There were 107 consultations for benign conditions (58%). Proportionally, the consultant spoke most (51.9% of total consultation time), followed by the patient (19.5%) and then companion (8.2%). Forty-eight (26.4%) patients brought a companion to the clinic but monopolisation of the consultation by the companion was rare. When a companion was present, there was more mutual eye gaze between the consultant and the patient. Interruptions were present in 23.6% of consultations and were associated with a significant increase of the length of the consultation. Table positioning did not seem to affect the dynamics of the outpatient consultation. Conclusion Companions are highly valuable for promoting patient engagement and their presence should be encouraged in surgical outpatients. Interruptions should be kept to a minimum to avoid unnecessary delays. Further studies should be conducted to investigate the effect of companions, interruptions and table positioning during a consultation on patient outcomes.

BACKGROUND At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

Sexual transmission is currently the main mode of transmission of the human immunodeficiency virus (HIV). In this study, 181 HIV-infected female cross-border travelers entering Yunnan province were recruited between 2003 and 2012. HIV RNAs were extracted from their frozen serum and gag-pol gene sequences were obtained for phylogenetic and recombination analyses. In total, 131 gag-pol gene sequences were obtained successfully, at a rate of 72.4%. The most prevalent subtypes were CRF01_AE, followed by CRF08_BC, subtypes B and C. The other 4 subjects were classified as undefined subtypes and other recombinants. The subtype distribution of intravenous drug users (IDUs) was significantly different from that of sexually transmitted infections (STIs) and unknown groups. The genetic distances of subtype B, C, and CRF01_AE strains were all close to the reference sequences from Yunnan province and Southeast Asian countries. Gene diversity and co-circulation of multiple subtypes were observed in female cross-border travelers, and CRF01_AE was the dominant epidemic subtype. The advantages of these subtype preferences for sexual transmission were obvious in HIV infection and transmission among this population. Our findings also suggest that close attention should be given to the HIV infection status of the female migrant population. In addition, description of their epidemic characteristics is significant for the surveillance and prevention of AIDS (acquired immunodeficiency syndrome) in the Yunnan province. This article is protected by copyright. All rights reserved.

Zonula occludens (ZO)-1 and ZO-2 are involved in epithelial polarity maintenance, gene transcription, cell proliferation and tumor cell metastasis. Regulating ZO-1/2 expression influences the early embryonic development of mice, but whether they are involved in oocyte maturation is still poorly understood. In the present study, the expression patterns of ZO-1 and ZO-2 in porcine cumulus cells and oocytes matured in vitro and early embryos from parthenogenetic activation were detected by qRT-PCR or Western blot, and then their roles in porcine oocyte maturation and early embryo development were investigated by shRNA technology. ZO-1 and ZO-2 were found to be expressed in cumulus cells, oocytes and early embryos, while ZO-1α+ was expressed only in cumulus cells, morula and blastocysts. During in vitro maturation (IVM), the abundance of ZO-1 and ZO-2 in oocytes was significantly higher than that in cumulus cells at 0 h (P 0.05). However, the blastocyst rate was reduced by treatment of COCs with ZO-1-shRNA1 but not ZO-2-shRNA2. The total cell number of blastocysts was decreased by downregulation of ZO-1 and ZO-2 (P 0.05). Altogether, the above results indicate that ZO-1 and ZO-2 display similar expression patterns during porcine oocyte IVM and are critical to porcine oocyte maturation and early embryonic development.

Studies on the association between healthy lifestyle and cancer risk are limited among the old Chinese population. The healthy lifestyle score was derived from smoking, drinking, diet, body mass index and physical activity among 23734 retired employees from the Dongfeng-Tongji Cohort. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). The rate advancement periods (RAPs) and the population attributable risk percentage (PAR%) were estimated to indicate the benefits of removing risk lifestyle factors. During a median follow-up of 8.16 years, 2023 cancer cases were identified. Compared with 0–2 points of the healthy lifestyle score, the HRs were 0.87 (95% CI: 0.76, 0.99), 0.83 (95% CI: 0.73, 0.94), and 0.74 (95% CI: 0.64, 0.86) for 3, 4, and 5 points, respectively, with the corresponding RAPs of −4.40 (95% CI: −8.39, −0.41), −5.84 (95% CI: −9.77, −1.90), and −9.14 (95% CI: −14.03, −4.25), respectively. Approximately 15% of incident cancer cases among total population and 22% among men would be prevented by following all 5 healthy lifestyle factors. The current study suggests that healthy lifestyle could reduce cancer risk in the retired Chinese population, especially in males.Key messagesHealthy lifestyle derived by smoking, drinking, diet, body mass index and physical activity presented a strong protective effect on cancer risk among the retired Chinese population, especially in males.We employed the rate advancement periods and the population attributable risk percentage to indicate the benefits of adopting healthy lifestyle and we found that following all 5 healthy lifestyle factors could delay the risk of developing cancer by 9.14 years and prevent 15% of incident cancer cases. Healthy lifestyle derived by smoking, drinking, diet, body mass index and physical activity presented a strong protective effect on cancer risk among the retired Chinese population, especially in males. We employed the rate advancement periods and the population attributable risk percentage to indicate the benefits of adopting healthy lifestyle and we found that following all 5 healthy lifestyle factors could delay the risk of developing cancer by 9.14 years and prevent 15% of incident cancer cases.

Cognitive impairment caused by diabetes has been gradually recognized. Generally, nicotinic acetylcholine receptors (nAChRs) play an important role in the pathogenesis in dementia disorders including Alzheimer's disease (AD). However, the expression of nAChRs in the brains of type 2 diabetes mellitus (T2DM) is unexplored. This study explored the alterations of nAChRs in the postmortem brains of patients with T2DM and brains of db/db mice. Morris water maze test was used to appraise the ability of spatial learning and memory; Western blotting and RT-qPCR were performed to determine the expressions of target protein and mRNA, respectively; TUNEL was used to detect the apoptosis of neurons. We found that the protein levels of nAChR α7 and α4 subunits were significantly decreased and the apoptosis rates in neurons elevated in the hippocampus of T2DM patients and db/db mice as comparison to controls. Furthermore, the db/db mice exhibited the impaired cognition, the elevated level of pro-apoptotic protein and the reduced level of anti-apoptotic and synaptic proteins. This study shows the lowered level of nAChR α7 and α4 subunits and the elevated apoptosis in the hippocampus of T2DM patients and db/db mice, which might help explain the impaired cognition in T2DM.

To investigate the neuroprotective role of silent mating-type information regulation 2 homolog 1 (SIRT1) in Alzheimer disease (AD), brain tissues from patients with AD and APP/PS1 mice as well as primary rat neurons exposed to oligomers of amyloid-β peptide were examined. The animals were treated with resveratrol (RSV) or suramin for 2 months. Cell cultures were treated with RSV, suramin, and the peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) stimulator ZLN005. Cells were transiently transfected with PGC-1α silencing RNA. The level of SIRT1 in brain tissues from patients with AD and APP/PS1 mice, including nuclear and mitochondrial proteins, as well as in primary neurons exposed to oligomers of amyloid-β peptide, was decreased. Overexpression of APP/PS1 impaired learning and memory of mice; produced more senile plaques, disrupted membranes, and resulted in broken or absent cristae of mitochondria in the brain; decreased levels of A disintegrin and metallopeptidase domain 10, beta-secretase 2, 8-oxoguanine DNA glycosylase-1, PGC-1α, and NAD+; and increased levels of beta-secretase 1 and apoptosis. Interestingly, these changes were attenuated significantly by RSV treatment but enhanced by suramin administration. By activating PGC-1α but inhibiting SIRT1, apoptotic cell death was significantly decreased; however, by activating SIRT1 but inhibiting PGC-1α with small interfering PGC-1α, these levels remained unchanged. These findings indicate that SIRT1 may protect against AD-associated neurotoxicity, which might involve PGC-1α regulation.

Background: Both the silent information regulator-1 (SIRT1) and α7 nicotinic acetylcholine receptors (α7 nAChR) play important roles in the pathogenesis of Alzheimer's disease (AD), but interactions between these two remain largely unknown. Our present aim was to determine whether the neuroprotective effect of SIRT1, due to inhibition of aggregation of the β-amyloid peptide (Aβ), involves activation of α7 nAChR. Methods: In present study, four-month-old mice carrying the APP/PS1 mutation were administered resveratrol (RSV, a stimulator of SIRT1) or suramin (an inhibitor) once daily for two months, following which their spatial learning and memory were assessed using the Morris water maze test. Deposits of Aβ in vivo were detected by near-infrared imaging (NIRI) and confocal laser scanning. SH-SY5Y cells over-expressing human APP670/671 (SH-SY5Y/APPSWE cells) were treated with RSV, suramin, U0126 (an inhibitor of the MAPK/ERK1/2 pathway) or methyllycaconitine (MLA, an inhibitor of α7 nAChR), as well as transiently transfected with SIRT1 silencing RNA. Levels of proteins and mRNA were determined by Western blotting and qRT-PCR, respectively. Findings: The results show that the learning and memory of mice carrying the APP/PS1 mutation had declined by 6 months of age and the levels of SIRT1 and α7 nAChR in their hippocampus and cortex were lowered. Activation of SIRT1 improved their spatial learning and memory and reduced the production and aggregation of Aβ in the hippocampus and cerebral cortex; whereas inhibition of SIRT1 had the opposite effects. In addition, activation of SIRT1 increased the levels of both α7 nAChR and αAPP in the brains these animals. Finally, activation of SIRT1 elevated the levels of phosphor-ERK1/2, while inhibition of ERK1/2 counteracted the increase in α7 nAChR caused by RSV. Interpretation: These findings indicate that neuroprotection by SIRT1 may involve increasing levels of α7 nAChR through activation of the MAPK/ERK1/2 signaling pathway. Funding Statement: This work was financed by grants from the Natural Science Foundation of China (U1812403), and the Foundation of Guizhou Province of China (2014-06, 2014-6008, 2016-4001). Declaration of Interests: The authors declare that they have no competing interests. Ethical Approval Statement: All animal experimental procedures were performed in accordance with the guidelines of the Animal Ethical and Experimental Committee of Guizhou Medical University.

Supplemental material, sj-docx-1-cll-10.1177_09636897221102902 for Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing by Andi Wang, Wenjun Li, Fei Zhao, Zhongzheng Zheng, Ting Yang, Sanbin Wang, Jinsong Yan, Jianpin Lan, Shengjin Fan, Mingfeng Zhao, Jianpin Shen, Xin Li, Tonghua Yang, Quanyi Lu, Ying Lu, Hai Bai, Haiyan Zhang, Dali Cai, Ling Wang, Zhiyang Yuan, Erlie Jiang, Fang Zhou and Xianmin Song in Cell Transplantation

BACKGROUND To reveal the mechanism underlying the effect of alpha7 nicotinic acetylcholine receptor (nAChR) on neurodegeneration in Alzheimer disease (AD), the influence of the receptor on recognition in APP/PS1 mice was evaluated by using its selective agonist (PNU-282987). MATERIAL AND METHODS APP/PS1 and wild-type (WT) mice were treated with PNU or saline, respectively, for 7 days at the ages of 6 and 10 months. RESULTS Morris water maze analysis showed that both at 6 and 10 months of age, PNU treatment enhanced the learning and memory of APP/PS1 mice. However, PNU treatment did not alter the number of senile plaques. Furthermore, a higher protein expression of Nrf2/HO-1, ADAM10, SYP, and SNAP-25, and a lower level of oxidative stress, were observed in the hippocampus of APP/PS1 mice treated with PNU compared with the control group. CONCLUSIONS The results indicated that the activation of alpha7 nAChR by PNU improved the learning and memory of mice carrying the APP/PS1 mutation, regulated the levels of enzymes that mediate APP metabolization to reduce ß-amyloid peptide damage, and decreased the level of oxidative stress and maintained synaptic plasticity, in which the mechanism might be enhancement of the Nrf2/HO-1 pathway.

Radiologic technologists face various types of patients during multi-detector computed tomography (CT) examinations. In emergency departments, it is common to have patients who cannot follow instructions for the examinations. The asymmetric axial view of the head CT might affect the correctness of the clinician’s diagnosis. This study aimed to assess the impact of head positioning on the image quality of head CT using two phantoms. All scans were performed on a 16-slice CT scanner. In the control group, the tilted angle of the phantoms was 0[Formula: see text], and no multiplanar reconstruction (MPR) was performed. In the experimental groups, the tilted angles of the phantoms were 5[Formula: see text], 10[Formula: see text] and 15[Formula: see text], respectively, and MPR was performed afterwards. The results showed that if the head was tilted during the head CT examinations, image asymmetry and artifacts appeared without MPR. After MPR, one phantom showed that there were significant differences and the other phantom showed no significant differences quantitatively in image symmetry and artifacts between experimental groups and the control group, while both phantoms showed no significant differences qualitatively in image symmetry and artifacts between experimental groups and the control group. Although MPR can correct the image asymmetry and artifacts caused by tilted head positioning to some extent, it consumes time. Therefore, technologists should position the head as exactly as possible when performing head CT examinations.

Xin-Ying Li,1 Shuang Yao,1 Yang-Ting He,1 Song-Qing Ke,1 Yi-Fei Ma,2 Ping Lu,3 Shao-Fa Nie,1 Shao-Zhong Wei,2 Xin-Jun Liang,3 Li Liu1 1Department of Epidemiology and Biostatistics, The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Gastrointestinal Oncology Surgery, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Abdominal Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Li LiuDepartment of Epidemiology and Biostatistics, the Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel/Fax +86-27-83693763Email liul2012@hust.edu.cnXin-Jun LiangDepartment of Abdominal Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel/Fax +86-27-87671663Email doctorlxj@163.comPurpose: This study was designed to investigate the prognostic value of the combination of high-sensitivity C-reactive protein, lymphocyte, and albumin in patients with resectable colorectal cancer.Patients and Methods: Seven-hundred-and-nineteen patients who underwent colorectal cancer resection in Hubei Cancer Hospital were included. Inflammation-Immunity-Nutrition score (0– 6) was constructed based on preoperative high-sensitivity C-reactive protein, lymphocyte, and albumin. Time-dependent receiver operating characteristic curve, decision curve, Kaplan-Meier survival curve, Cox regression, and C-index were conducted to detect the prognostic values of inflammation-immunity-nutrition score. The prognostic values of inflammation-immunity-nutrition score in different subgroups by sex, location of tumor, pathologic stage, and KRAS mutation were also explored. The prognostic performance of inflammation-immunity-nutrition score was further compared with that of other traditional prognostic indicators.Results: The median follow-up time was 40 months. High inflammation-immunity-nutrition score (> 2 scores) presented worse survival, with the adjusted hazard ratios (95% confidence intervals) of 3.106 (2.202– 4.380) for overall survival and 2.105 (1.604– 2.764) for disease-free survival. Besides, the associations of high inflammation-immunity-nutrition score with overall survival were even stronger in cases with wild type KRAS, with the adjusted hazard ratios (95% confidence intervals) of 4.018 (2.355– 6.854). Considering the AUCs, C-indices, and hazard ratios estimates, inflammation-immunity-nutrition score presented better prognostic performance than high-sensitivity modified Glasgow prognostic score, high-sensitivity C-reactive protein to albumin ratio, prognostic nutrition index, carcinoembryonic antigen, and carbohydrate antigen 19-9 for overall survival.Conclusion: Inflammation-immunity-nutrition score might serve as a powerful prognostic score in patients with colorectal cancer for overall survival, particularly in patients with wild type KRAS.Keywords: high-sensitivity C-reactive protein, survival, colorectal cancer, inflammation

The mix-based activated carbon derived from corn stalk and walnut shell was prepared by chemical activation method using phosphoric acid as the activator. The optimized conditions for preparation were obtained by the orthogonal experiment, the characterizations of the activated carbon were performed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy(FTIR), Boehm’s titration method and nitrogen adsorption. For the prepared mix-based activated carbon, the highest iodine number, methylene blue number and BET surface area are 720.5 mg/g, 195.0 mg/g and 1187 m2/g, respectively, and the pores are mainly mesopores. The mix-based activated carbon shows the higher adsorption capacity for malachite green than the raw materials, the activated carbons prepared only from corn stalk or walnut shell and the commercial activated carbon. The kinetics and thermodynamics of the adsorption can be satisfactorily described by the Pseudo-second-order kinetic model and the Langmuir isotherm model, separately.

Post-operative hypoxia is a fairly common clinical complication with severe consequences that can result in permanent organ damage, increased morbidity, increased cost, poor prognosis, and increased fatality. To effectively understand the factors that contribute to such a disease, we conducted a study to determine if obesity is a risk factor of post-operative hypoxia. A thorough search for articles was conducted on various databases. A total of 15658 potential studies were identified out of which 8 were included in this meta-analysis. Data was extracted and analyzed which included 2500 subjects; 1265 subjects in the obese group, and 1235 subjects in the lean group. The combined effect size was 0.19. The results showed that the incidence of post-operative hypoxia in obese was not significantly higher than the lean patients. In conclusion, the meta-analysis reveals that there is no significant correlation between obesity and postoperative hypoxia. Key words: Meta-analysis; Hypoxia; Obesity; Postoperative; Risk factor Citation: Ting Y, Bin L. Association of obesity with postoperative hypoxia: A meta-analysis. Anaesth. Pain intensive care 2021;25(1):55-62. DOI: 10.35975/apic.v25i1.1335 Received: 18 February 2020, Reviewed: 16 March 2020, Accepted: 30 April 2020

Background & aimsImpaired exercise tolerance is a clinical feature of chronic obstructive pulmonary disease (COPD) associated with disease progression and increased mortality. The 6-minute walk test (6MWT) is a reliable and widely used measure of exercise capacity. However, it is not commonly used in primary medical institutions because it requires a suitable venue and professional training. Developing a simple tool to assess exercise tolerance is important. Molecular biomarkers show potential for evaluating the clinical outcomes (mortality, exacerbation) of COPD patients. The aim of this study was to identify simple and effective biomarkers to predict poor exercise tolerance in COPD patients.MethodsTen genes were selected by weighted correlation network analysis and differentially expressed gene analysis. Validation in an independent dataset led to the identification of PLA2G7, which was verified as a potential biomarker in COPD by bioinformatics analysis. The concentration of lipoprotein-associated phospholipase A2 (Lp-PLA2), which is encoded by the PLA2G7 gene, was assessed by enzyme-linked immunosorbent assay in a prospective validation cohort. The predictive capacity of Lp-PLA2 for 6-minute walk distance (6MWD)

Chronic fluorosis is an endemic disease that severely impairs human health. Studies have proved that the change of various receptors in the body is attributed to excessive fluoride intake. For instance, it will reduce the expression of acetylcholine receptor that affects the release of neurotransmitters and will cause changes of N-methyl-D-aspartic acid receptor that impacts cellular Ca2+ influx and of advanced glycation end product receptor, augmenting the inflammatory response of the body, etc. These changes are the key mechanism of multi-system injuries caused by fluorosis. With the increased attention on more and more receptors in recent years, the role they played in the pathogenesis of chronic fluorosis is becoming ever more essential. Therefore, an in-depth study of its mechanism of action is possibly vital to uncover the injury of chronic fluorosis and can also provide a theoretical basis for prevention and clinical treatments.

Introduction: Recent studies have shown elimination of senescent cells, so-called "senolysis" has the potential to become a novel therapy for aging and age-related disorders. However, there is no senolytic drug available in clinical settings currently. Purpose: The present study was aimed to identify a novel senolytic reagent effective for cardiometabolic disease among compounds already available in clinical settings. Here we identified a compound called "seno-7284" which exhibits senolytic effect in murine models of aging and age-related cardiometabolic disorders. Methods: We generated diet-induced obese(DIO) mice model by imposing high-fat diet, atherosclerotic mice model by imposing western diet to ApoE knockout mice. We administered seno-7284 mixed in the diet (0.03% w/w) to each mouse model for 1, 2 or 4 weeks. We harvested tissue samples for molecular biological analysis after measuring glucose/insulin tolerance. We also administered seno-7284 to Zmpste24 homozygous knockout mice as a progeroid mice model from 12-week-old to measure lifespan and to wild-type mice from 1-year-old for 20 weeks to measure physical function. Results: Seno-7284 reduced accumulation of senescent cells in visceral adipose tissue of DIO mice as senescence-associated beta-galactosidase (SA-beta-gal) staining exhibits (figure(fig) a), resulting in improvement of glucose metabolism (fig b). We also found seno-7284 reduced accumulation of senescent cells in the aorta of atherosclerotic mice model (fig c) and inhibited advancing atherosclerosis (fig d). Furthermore, Seno-7284 improved lifespan of progeroid mice (fig e) and physical function of aged mice (fig f). Further analysis including RNA-seq speculated seno-7284 stimulates endogenous senolytic function of immune cells. Conclusion: Our results indicate that seno-7284 would become a promising senolytic drug that exhibits novel therapeutic machinery for aging and age-related cardiometabolic diseases.

Protein-glutaminase (PG) is a promising protein deaminase. It only hydrolyzes the side chain amido groups of protein-bound to generate ammonia and protein-L-glutamic acid and does not catalyze any other undesirable changes in protein structures. Deamidation of proteins via PG can influence the solubility, emulsification, foaming, and gelation properties of proteins, which are important properties for some food proteins. Therefore, there is great potential for the application of PG in the food industry. PG is derived from Chryseobacterium proteolyticum (C. proteolyticum); however, wild strains are difficult to industrialize because of their low levels of enzyme production. In this article, we studied different strategies for PG expression in B. subtilis. Results showed that PG produced from C. proteolyticum could be successfully secreted in B. subtilis WB800N, and actively secreted in B. subtilis 168(BS168) or DB403 containing a pro-peptide (pro-PG). The secreted PG from B. subtilis WB800N was inactive unless digested by exogenous proteases, such as trypsin, alkaline protease, and neutral protease. However, active PG was secreted by the self-processing of BS168 and DB403. The specific activity of purified PG reached 20.9 U/mg. PG showed maximum activity at pH 5.5, 55 °C and more than 80% of PG activity was retained within a range of pH 3.5–6.5. When Cbz-Gln-Gly was used as the substrate, PG activity was 31.1 ± 0.9 μM min−1 mg−1. Mg2+, Ca2+, and Zn2+ stabilized and even activated PG activity. These strategies concerning PG expression in B. subtilis and the enzymatic properties of PG provide efficient alternatives for PG research and contribute to the industrial-scale production of PG.

Caecal volvulus represents 25–40% of all colonic volvulus. Symptoms include abdominal distension, constipation, nausea and vomiting where it may be intermittent. Abdominal X-rays and computed tomography (CTs) may help with diagnosis and recommended treatment is resection of mobile caecum. A 70-year old comorbid woman with previous open bariatric surgery and known incisional hernia presented with symptoms of bowel obstruction. CT showed caecal volvulus contained within the ventral hernia confirmed intra-operatively. Patient recovered well and was discharged on Day 6 of admission. This is the second case described in literature of a caecal volvulus occurring in an incisional hernia. The altered normal anatomy may have contributed to caecal mobility. Diagnosis of caecal volvulus can be challenging, more so in the presence of a more clinically apparent pathology. We present a second known case of caecal volvulus in a giant incisional hernia, where there were unique challenges to management.

Background To reveal the underling molecular mechanism in brain damage induced by chronic fluorosis, the neurotoxicity and its correlation were investigated by transcriptomics and proteomics. Methods Sprague-Dawley rats were treated with fluoride at different concentrations (0, 5, 50 and 100 ppm, prepared by NaF) for 3 months. Spatial learning and memory were evaluated by Morris water maze test; neuronal morphological change in the hippocampus was observed using Nissl staining; and the level of oxidative stress including reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by biological methods. The high-throughput transcriptome sequencing (RNA-Seq) and tandem mass tag (TMT) proteomic sequencing were performed to detect the expression of differentially expressed genes and proteins, respectively. Results The results showed that compared with control group, rats exposed to high-dose fluoride exhibited declined abilities of learning and memory, decreased SOD activity and increased ROS and MDA levels, with lighter colored Nissl bodies. A total of 28 important differentially expressed genes (DEGs) were screened out by transcriptomics. Then, functional enrichment analyses showed that upregulated proteins enriched in cellular transport, while downregulated proteins enriched in synapse-related pathways. Thirteen corresponding DEGs and DAPs (cor-DEGs-DAPs) were identified by differential expressions selected with positively correlated genes/proteins, most of which were related to neurodegenerative changes and oxidative stress response. Conclusion These results provide new omics evidence that rats chronically exposed to high-dose fluoride can induce neurotoxicity in the brains through changes in the cholinergic pathway and oxidative stress.

AimsThis study was designed to explore the expression and distribution of silent information regulator 1 (SIRT1) and superoxide dismutase 1 (SOD-1) in various regions of the brains of patients with Alzheimer's disease (AD), as well as to assess potential correlations between the levels of these proteins and also between these proteins and the Braak stage of AD.MethodsIn the temporal and frontal cortices, hippocampus and cerebellum of 10 patients with AD and 10 age-matched control subjects, expression of SIRT1 and SOD-1, together with histopathology, were assessed by immunohistochemical and immunofluorescent stainings. Relationships between variables were examined with the Pearson correlation test.ResultsThe numbers of both SIRT1-positive and SOD-1-positive neurons and integrated optical density of immunohistochemical staining for these proteins in the temporal and frontal cortices, and hippocampus of patients with AD were significantly decreased than those in corresponding controls. In the case of the cerebellum, very weak expression of SIRT1 and obvious expression of SOD-1 were observed in granule cells, with no significant difference between AD and the control group. Interestingly, the protein levels between SIRT1 and SOD-1, as well as the level of SIRT1 or SOD-1 and Braak stage, were significantly correlated in neurons in all regions of the AD brains investigated except for the cerebellum.ConclusionsThese findings indicate that the reduced level of SIRT1 in the brains of patients with AD may be related to the decline in SOD-1 and neuropathological changes of this disorder.

Aim: The aim of this study is to investigate whether lithium chloride (LiCl) can regulate glycogen synthase kinase-3β (GSK3β)/nuclear factor E2 related factor（Nrf2）/heme oxygenase-1 (HO-1) pathway ...

Ribonucleotide reductases (RNRs) convert ribonucleotides to deoxynucleotides, a process essential for DNA biosynthesis and repair. Class Ia RNRs require two dimeric subunits for activity: an α2 subunit that houses the active site and allosteric regulatory sites and a β2 subunit that houses the diferric tyrosyl radical cofactor. Ribonucleotide reduction requires that both subunits form a compact α2β2 state allowing for radical transfer from β2 to α2. RNR activity is regulated allosterically by dATP, which inhibits RNR, and by ATP, which restores activity. For the well-studied Escherichia coli class Ia RNR, dATP binding to an allosteric site on α promotes formation of an α4β4 ring-like state. Here, we investigate whether the α4β4 formation causes or results from RNR inhibition. We demonstrate that substitutions at the α–β interface (S37D/S39A-α2, S39R-α2, S39F-α2, E42K-α2, or L43Q-α2) that disrupt the α4β4 oligomer abrogate dATP-mediated inhibition, consistent with the idea that α4β4 formation is required for dATP's allosteric inhibition of RNR. Our results further reveal that the α–β interface in the inhibited state is highly sensitive to manipulation, with a single substitution interfering with complex formation. We also discover that residues at the α–β interface whose substitution has previously been shown to cause a mutator phenotype in Escherichia coli (i.e. S39F-α2 or E42K-α2) are impaired only in their activity regulation, thus linking this phenotype with the inability to allosterically down-regulate RNR. Whereas the cytotoxicity of RNR inhibition is well-established, these data emphasize the importance of down-regulation of RNR activity.

Expressions of N-methyl-d-aspartic acid receptors (NMDARs) in the brains of rats and primary neurons exposed to high fluoride were investigated. Sprague-Dawley rats were divided randomly into a fluorosis group (50ppm fluoride in the drinking water for 6 months) and controls (

PURPOSE: The purpose of this study is to identify the immediate effect of posterior pelvic tilt taping on anterior pelvic inclination, gait function, and balance in chronic stroke patients. METHODS: Fourteen chronic stroke subjects were enrolled in this study. Subjects who consented to participate in this cross-over experiment were assigned three interventions: posterior pelvic tilt taping, placebo taping, and no taping, in random order. After tape application, subjects were asked to complete: 1) Anterior pelvic tilt measurement, 2) 10-Meter Walk test, and 3) Limits of stability (LOS) test. To eliminate the learning effect of the tape after tearing off the tape, a 10 minute break was given between posterior pelvic tilt taping intervention and placebo taping intervention. RESULTS: Significant decreases were observed for the anterior pelvic inclination on both sides after posterior pelvic tilt taping application compared with placebo taping and no taping application (p .05). CONCLUSION: Posterior pelvic tilt taping in chronic stroke patients decreases the inappropriate anterior pelvic inclination immediately and improves gait function, but it has little effect on balance.

Pelvic organ prolapse (POP) is a common condition affecting older women. POP can cause hydronephrosis in some patients. Although rare, especially in the subset of patients with vaginal vault prolapse, unrecognized obstructive hydronephrosis can result in renal impairment and urosepsis. We present a case of a 69-year-old female with obstructive urosepsis on a background of vaginal vault prolapse. The case highlights the importance of early recognition and intervention of obstructive urosepsis in patients with severe POP disease. Level of evidence: Not applicable for this multicentre audit.

To satisfy the need to accurately monitor emotional stress, this paper explores the effectiveness of the attention mechanism based on the deep learning model CNN (Convolutional Neural Networks)-BiLSTM (Bi-directional Long Short-Term Memory) As different attention mechanisms can cause the framework to focus on different positions of the feature map, this discussion adds attention mechanisms to the CNN layer and the BiLSTM layer separately, and to both the CNN layer and BiLSTM layer simultaneously to generate different CNN–BiLSTM networks with attention mechanisms. ECG (electrocardiogram) data from 34 subjects were collected on the server platform created by the Institute of Psychology of the Chinese Academy of Science and the researches. It verifies that the average accuracy of CNN–BiLSTM is up to 0.865 without any attention mechanism, while the highest average accuracy of 0.868 is achieved using the CNN–attention–based BiLSTM.

Background 100 mg rectal nonsteroidal anti-inflammatory drugs (NSAIDs) and pancreatic stents both significantly reduce the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Direct comparison of randomized controlled trials (RCTs) between them in high-risk patients is absent. We conducted this network meta-analysis to indirectly compare the efficacies of 100 mg rectal NSAIDs and pancreatic stents in preventing post-ERCP pancreatitis (PEP) in high-risk patients and help us decide which is preferred in clinical practice. Methods A comprehensive search was done to identify RCTs published in English full-text. Interventions included 100 mg rectal NSAIDs (diclofenac or indomethacin) and pancreatic stents. Only studies with high-risk patients of PEP were included. Meta-analyses of NSAIDs and pancreatic stents were conducted respectively. A network meta-analysis using the Bayesian method was performed. Results We included 14 RCTs, 8 on pancreatic stents and 6 on 100 mg rectal NSAIDs in high-risk patients. There was no direct comparison between them. After excluding an outlier study on NSAIDs (n = 144), meta-analyses showed they both significantly and statistically reduced the incidence of PEP in high-risk patients (pancreatic stents: n = 8 studies, random-effects risk ratio (RR)0.41, 95%CI 0.30-0.56, I = 0%; NSAIDs: n = 5 studies, random-effects RR 0.37, 95%CI 0.25-0.54, I = 0%). And network meta-analysis showed efficacy of 100 mg rectal NSAIDs was equal to pancreatic stents (random-effects RR 0.94, 95%CI 0.50-1.8). Conclusions The efficacy of 100 mg rectal NSAIDs (diclofenac or indomethacin) seems equally significant to pancreatic stents in preventing PEP in high-risk patients. Considering the cost-effectiveness and safety, 100 mg diclofenac or indomethacin may be preferred.

Protection of Resveratrol (RSV) against the neurotoxicity induced by high level of fluoride was investigated. Sprague-Dawley (SD) rats and their offspring, as well as cultures of primary neurons were divided randomly into four groups: untreated (control); treated with 50 mg RSV/kg/ (once daily by gavage) or (20 M in the cultured medium); exposed to 50 ppm F- in drinking water or 4 mmol/l in the cultured medium; and exposed to fluoride then RSV as above. The adult rats were treated for 7 months and the offspring sacrificed at 28 days of age; the cultured neurons for 48 h. For general characterization, dental fluorosis was assessed and the fluoride content of the urine measured (by fluoride-electrode) in the rates and the survival of cultured neurons monitored with the CCK-8 test. The spatial learning and memory of rats were assessed with the Morris water maze test. The levels of α7 and α4 nicotinic acetylcholine receptors (nAChRs) were quantified by Western blotting; and the activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) and H2O2 assayed biochemically. The results showed that chronic fluorosis resulted in the impaired learning and memory in rats and their offspring, and more oxidative stress in both rat brains and cultured neurons, which may be associated the lower levels of α7 and α4 nAChR subunits. Interestingly, RSV attenuated all of these toxic effects by fluorosis, indicating that protection against the neurotoxicity of fluoride by RSV might be in mechanism involved enhancing the expressions of these nAChRs.

Second primary breast cancer (SPBC) is becoming one of the major obstacles to breast cancer (BC) control. This study was aimed to determine the trend of SPBC incidence over time and the risk of developing SPBC in site-specific primary cancer survivors in the United States. The Surveillance, Epidemiology, and End Results (SEER) 13 registry (1992-2015) was used to identify SPBC patients with previous malignancies. Standardized incidence ratio (SIR) was computed to compare the incidence rates of the observed cases of SPBC in cancer survivors over the expected cases in the general population. Elevated risk of SPBC was observed in women with previous BC (SIR = 1.74) or thyroid cancer (SIR = 1.17). Women with initial skin melanoma in older age (≥50 years) (SIR = 1.11), or White race (SIR = 1.11) presented an elevated incidence of SPBC than the general female population. Besides, Asian/Pacific Islander (API) women with cancer of corpus uteri, ovary, bladder, or kidney were prone to developing SPBC when compared with the general population, with SIRs of 1.61, 1.35, 1.48, and 1.70, respectively. Male BC patients showed profound risk of developing SPBC (SIR = 34.86). Male leukemia patients also presented elevated risk of developing SPBC (SIR = 2.06). Our study suggests significant increase of SPBC in both sexes in the United States. Elevated risk of SPBC exists in survivors with primary BC, female thyroid cancer, male leukemia, and API female cancer patients with primary genitourinary cancer. Our study is helpful in developing strategies for BC control and prevention on specific first primary cancer survivors with an elevated risk of SPBC.

Background Oily skin is one of the most common dermatological complaints. Oily skin may be accompanied by enlarged pores, acne, and seborrheic dermatitis. Moreover, oily skin has negative effects on self-perception. Most therapeutic approaches used to treat oily skin have had varying degrees of efficacy and include topical treatments, such as photodynamic therapy and lasers. However, certain of these therapies for oily skin may lead to severe side effects. With the expanding use and high safety profile of botulinum toxin type A (BoNT-A), its use in the treatment of oily skin has caused significant concerns; moreover, relevant reports have gradually accumulated to address the efficacy of BoNT-A and explore its mechanisms of action. Aims The objective of this article was to review the efficacy and possible treatment mechanisms of BoNT-A on oily skin. Methods A retrospective review of the published data was conducted. Results Most studies have suggested that the intradermal injection of BoNT-A decreased sebum production and pore size. Furthermore, this treatment attained high patient satisfaction without significant side effects. BoNT-A effectively decreased sebum production and excretion, which was in keeping with previous studies, possibly via its blockade of cholinergic signaling and its neuromodulatory effects. Conclusions Intradermal BoNT-A injection may represent a promising new treatment for oily skin and other relevant dermatological problems, such as enlarged pores, acne, and seborrheic dermatitis. Further study is still needed to determine the specific mechanisms of BoNT-A and the optimal injection techniques and doses for oily skin and other relevant cosmetic concerns.

Background Heart conditions impose physical, social, financial and health-related quality of life limitations on individuals in Brazil. Objectives This study assessed the economic burden of four main heart conditions in Brazil: hypertension, heart failure, myocardial infarction, and atrial fibrillation. In addition, the cost-effectiveness of telemedicine and structured telephone support for the management of heart failure was assessed. Methods A standard cost of illness framework was used to assess the costs associated with the four conditions in 2015. The analysis assessed the prevalence of the four conditions and, in the case of myocardial infarction, also its incidence. It further assessed the conditions’ associated expenditures on healthcare treatment, productivity losses from reduced employment, costs of providing formal and informal care, and lost wellbeing. The analysis was informed by a targeted literature review, data scan and modelling. All inputs and methods were validated by consulting 15 clinicians and other stakeholders in Brazil. The cost-effectiveness analysis was based on a meta-analysis and economic evaluation of post-discharge programs in patients with heart failure, assessed from the perspective of the Brazilian Unified Healthcare System (Sistema Unico de Saude). Results Myocardial infarction imposes the greatest financial cost (22.4 billion reais/6.9 billion USD), followed by heart failure (22.1 billion reais/6.8 billion USD), hypertension (8 billion reais/2.5 billion USD) and, finally, atrial fibrillation (3.9 billion reais/1.2 billion USD). Telemedicine and structured telephone support are cost-effective interventions for achieving improvements in the management of heart failure. Conclusions Heart conditions impose substantial loss of wellbeing and financial costs in Brazil and should be a public health priority.

Background The costs for treating coronary artery disease (CAD) are high worldwide. We performed a prespecified analyses of cost-effectiveness of three therapeutic strategies for multivessel CAD. Methods From May 1995 to May 2000, a total of 611 patients were randomly assigned to coronary artery bypass graft (CABG), n = 203; percutaneous coronary intervention (PCI), n = 205; or medical treatment (MT), n = 203. This cost analysis study was based on the perspective of the Public Health Care System. Initial procedural and follow-up costs for medications, cardiology examinations, and hospitalizations for complications were calculated after randomization. Life-years and quality-adjusted life years (QALYs) were used as effectiveness measures. Incremental cost-effectiveness ratios (ICER) were obtained by using nonparametric bootstrapping methods with 5000 resamples. Results Initial procedural costs were lower for MT. However, the subsequent 5-year cumulative costs were lower for CABG. Compared with baseline, the three treatment options produced significant improvements in QALYs. After 5 years, PCI and CABG had better QALYs results compared with MT. The ICER results favored CABG and PCI, and favored PCI over CABG in 61% of the drawings. On the other hand, sensitivity analysis showed MT as the preferred therapy compared with CABG and PCI, in the analysis considering higher costs. Conclusions At 5-year follow-up, the three treatment options yielded improvements in quality of life, with comparable and acceptable costs. However, despite higher initial costs, the comparison of cost-effectiveness after 5 years of follow-up among the three treatments showed both interventions (CABG and PCI) to be cost-effective strategies compared with MT. Trial registration ISRCTN, ISRCTN66068876, Registered 06/10/1994, http://www.controlled-trials.com/ISRCTN66068876

In the study, we examined whether the silent information regulator 1 (SIRT1) can attenuate oxidative stress in the brains of mice carrying the APP/PS1 double mutation and/or in primary neonatal rat neurons exposed to oligomers of amyloid-β peptide (AβOs). Starting at 4 or 8 months of age, the transgenic mice were treated with resveratrol (RSV, a stimulator of SIRT1) or suramin (an inhibitor) (each 20 mg/kg BW/day) for two months. The primary neurons were exposed to AβOs (0.5 μM) for 48 h and thereafter RSV (20 μM) or suramin (300 mg/ml) for 24 h. Cell viability was assessed by the CCK-8 assay; SIRT1 protein and mRNA determined by western blotting and real-time PCR, respectively; senile plaques examined immunohistochemically; ROS monitored by flow cytometry; and the contents of OH-, H2O2, O2·-, and MDA, and the activities of SOD and GSH-Px measured by standard biochemical procedures. In comparison to wild-type mice or untreated primary neurons, the expression of SIRT1 was significantly lower in the brains of APP/PS1 mice or neurons exposed to AβOs. In these same systems, increased numbers of senile plaques and a high level of oxidative stress were apparent. Interestingly, these two latter changes were attenuated by treatment with RSV, but enhanced by suramin. These findings indicate that SIRT1 may be neuroprotective.

We introduce a new approach for jet physics studies using subtracted cumulants of jet substructure observables, which are shown to be insensitive to contributions from soft-particle emissions uncorrelated with the hard process. Therefore, subtracted cumulants allow comparisons between theoretical calculations and experimental measurements without the complication of large background contaminations such as underlying and pileup events in hadron collisions. We test our method using subtracted jet mass cumulants by comparing Monte Carlo simulations to analytic calculations performed using soft-collinear effective theory. We find that, for proton-proton collisions, the method efficiently eliminates contributions from multiparton interactions and pileup events. We also find within theoretical uncertainty that our analytic calculations are in good agreement with the subtracted cumulants calculated by using ATLAS jet mass measurements.

This paper proposes a novel method for evaluating the video-based learning performance by using brain computer interface (BCI). We develop Interactive Brain Tagging system (IBTS) to collect learns’ physiological affective metadata: attention. IBTS uses the EEG headset to measure learners’ brainwave and convert it into the evaluable attention value. When learners are watching video, their attention values are recorded every one second and marked in each corresponding video clip. We visaulize the variation of attention and tried to find out the continuous duration of higher attention level in a video. We used a 15 min’ video to conduct the experiment with 31 subjects. The result presented the difference of individual and collective attention duration. Moreover, in our case, the collected result suggested that the appropriate video time with higher attention may locate in 232 s.

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by aberrant tau protein hyperphosphorylation, which eventually leads to the formation of neurofibrillary tangles. Hyperphosphorylated tau protein is considered as a vital factor in the development of AD and is highly associated with cognitive impairment. Therefore, it is recognized to be a potential therapeutic target. Quercetin (QUE) is a naturally occurring flavonoid compound. In the present study, the inhibitory effect of QUE on okadaic acid (OA)-induced tau protein hyperphosphorylation in HT22 cells was explored. Western blotting results indicated that QUE significantly attenuated OA‑induced tau protein hyperphosphorylation at the Ser396, Ser199, Thr231 and Thr205 sites. Further experiments demonstrated that QUE inhibited the activity of cyclin‑dependent kinase 5 (CDK5), a key enzyme in the regulation of tau protein, and blocked the Ca2+‑calpain‑p25‑CDK5 signaling pathway. These observations indicate the ability of QUE to decrease tau protein hyperphosphorylation and thereby attenuate the associated neuropathology. In conclusion, these results support the potential of QUE as a therapeutic agent for AD and other neurodegenerative tauopathies.

To reveal the molecular mechanism of deficit in learning and memory induced by chronic fluorosis, the expression of muscarinic acetylcholine receptors (mAChRs) and oxidative stress were investigated. Sixty Sprague-Dawley (SD) rats were divided randomly into two groups (30 cases in each), i.e., the control group (0.5 ppm fluoride in drinking water) and the fluoride group (50 ppm fluoride) for 10 months of treatment. The pups born from SD mothers with or without chronic fluorosis were selected at postnatal days 1, 7, 14, 21 and 28 for experiments (10 for each age). Spatial learning and memory were evaluated by Morris water maze test. The expressions of M1 and M3 mAChRs at the protein and mRNA levels were determined by Western blotting and real-time PCR, respectively. In addition, the contents of (·)OH, H2O2, O2(·-) and malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in brains were quantitated by biochemical methods. Our results showed that as compared to controls, the abilities of learning and memory were declined in the adult rats and the offspring rats of postnatal day 28 in the fluoride groups; the expressions of both M1 and M3 mAChRs were significantly reduced at protein and mRNA levels; and the levels of (·)OH, H2O2, O2(·-) and MDA were significantly increased, while the activities of SOD and GSH-Px decreased. Interestingly, the decreased protein levels of M1 and M3 mAChRs were significantly correlated with the deficits of learning and memory and high level of oxidative stress induced by chronic fluorosis. Our results suggest that the mechanism for the deficits in learning and memory of rats with chronic fluorosis may be associated with the decreased expressions of M1 and M3 in mAChRs, in which the changes in the receptors might be the result of the high level of oxidative stress occurring in the disease.