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Amyloid-β (Aβ) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aβ produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aβ clearance remain largely unknown. The kidney is thought to be responsible for Aβ clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aβ in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aβ clearance via the kidney were assessed. We detected Aβ in the kidneys and urine of both humans and animals and found that the Aβ level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aβ deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aβ levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aβ from the blood, suggesting that facilitation of Aβ clearance via the kidney represents a novel potential therapeutic approach for AD.

Background Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. Methods This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. Results Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p p p p p p p p p p Conclusions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

Hyperphosphorylated tau is an important pathological agent in Alzheimer’s disease (AD). Tau effluxes from the brain to the blood could potentially stimulate the production of naturally occurring antibodies (NAbs). We aimed to investigate whether NAbs to tau (NAbs-tau) was generated in human blood and to figure out the alteration of plasma NAbs-tau level in AD patients. About 192 AD patients and 192 age-matched and non-demented controls (NC) were enrolled in the present study. Immunofluorescence staining and western blot assays were used to confirm the existence of NAbs-tau in human blood. The plasma level of NAbs-tau in NC and AD group was analyzed by ELISA. Immunofluorescence staining and western blot assays confirmed the existence of NAbs-tau in human blood. However, no significant difference in the plasma level of NAbs-tau was observed between NC and AD group. Furthermore, the plasma level of NAbs-tau had no significant correlation with MMSE scores. The present study confirmed that NAbs-tau exists in human blood but does not differ in level between the NC and AD group. Plasma NAbs-tau is not a reliable biomarker for AD. Refereed/Peer-reviewed

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19. Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13; controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81; controls: 3.15±0.39, p

Study Objective To describe the new“chopsticks technique”single-site laparoscopic surgery technique, and compare the Perioperative outcomes of “chopsticks technique” single-site laparoscopy versus traditional laparoscopy for endometrial cancer. Design A retrospective case-control study based on propensity score matching. Setting Department of gynecology at a tertiary medical center. Patients or Participants From August 2018 to August 2020, a total of 78 patients who accepted the laparoscopic staging of endometrial cancer were retrospectively analyzed. 26 cases conducted “chopsticks technique”single-site laparoscopic surgery(LESS) were matched with a cohort of 52 cases who underwent traditional multi-site laparoscopic surgery (CLS). Interventions A propensity score matching was performed to reduce the bias due to the imbalanced baseline features between the two groups and the perioperative outcomes were compared between matched cohorts. Measurements and Main Results A retrospective case–control study was conducted matched by age, BMI, history of surgery, FIGO staging. After matching, the variables were well balanced with no differences at baseline between groups. The operations in both groups were successfully completed without conversion to laparotomy. There were no statistically significant differences in the amount of intraoperative blood loss, pelvic lymph nodes, number of para-aortic lymph nodes removed, postoperative exhaust time, postoperative indwelling drainage time, postoperative hospital stay between the two groups (P>0.05). Meanwhile, Compared with the traditional multi-port laparoscopic group CLS, the “chopsticks technique” single-site laparoscopic group (LESS) has longer operation time (197.3±55.7 vs. 164.7±62.7, p=0.043) , a pain score of 24-hour after surgery (3 (3,2) vs3 (4,2) , p=0.031) and a more satisfactory postoperative cosmetic effect (6.9±0.5 vs. 6.12±0.7, p=0.023) , of which the difference was statistically significant (P Conclusion It is safe and feasible for staging endometrial cancer to employ the“chopsticks technique”single-site laparoscopic with minimum scars from abdominal incisions, which results in less pain and outstanding cosmetic effects. However, further prospective, randomized studies with larger samples are needed.

Previous studies have suggested that cardiovascular functions might play a critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship among heart function, blood flow of cerebral vessels, and AD remains unclear. In the present study, AD patients (n = 34) and age- and gender-matched cognitively normal controls (n = 34) were recruited. Demographic and comorbidity information was collected. The ejection fraction was measured using echocardiography, and the mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar artery (BA), left terminal internal carotid artery (LTICA), and right terminal internal carotid artery (RTICA) were measured using transcranial Doppler. The data of lacunae, white matter changes, and plaques in the aortic arch and carotid arteries were collected from brain magnetic resonance imaging and computed tomography angiography images. Compared with normal controls, AD patients had lower ejection fractions and cerebral blood flow velocities and higher RI and PI in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid arteries. In the multivariate logistic regression analysis, the ejection fraction and the mean velocity of the BA and LTICA were independently associated with AD after adjusting for age, gender, education, vascular risk factors, arterial plaques, and brain ischemic lesions detected in the brain images. These findings suggest that heart function and vascular condition may play important roles in AD pathogenesis. Improving cardiovascular functions could be a promising approach for the prevention and treatment of AD.

Study Objective This study evaluated the feasibility, safety and short-term clinical outcomes from extraperitoneal sacral hysteropexy by transvaginal natural orifice transluminal endoscopic surgery in treating uterine prolapse. Design Retrospective study. Setting The First Affiliated Hospital of Third Military Medical University, Chongqing, China Patients or Participants The medical records of patients with POP-Q stage 2 or greater uterine prolapse who were treated with vNOTES-ESH between December 2016 to June 2018(to ensure 1-year follow-up or more) in the Southwest Hospital at the Third Military Medical University were reviewed retrospectively. Interventions Extraperitoneal sacral hysteropexy were performed by vNOTES. Measurements and Main Results 21 patients underwent surgery; 20 were successfully completed, and one that could not maintain pressure at the extraperitoneal cavity site due to peritoneal rupture during surgery who underwent multi-port laparoscopic surgery. Median patient age was 50 years. The body mass index (BMI) was 23.7 kg/m2, the median operative time was 126 min, and the median intraoperative blood loss was 60 mL. One case had presacral hemorrhage that was circumvented by bipolar electrocoagulation. Preoperative POP-Q scores were: Aa-0, Ba-1, C-2, Ap-3, and Bp-3. The average post-operative follow-up was 12 months. The POP-Q scores were: Aa-2, Ba-2, C-7, Ap-3, and Bp-3. Associated symptoms disappeared or improved significantly without sexual discomfort or pain on intercourse, mesh erosion, exposure, infection or other complications. The objective cure rate was 100 percent. Conclusion vNOTES was a feasible approach in completing extraperitoneal sacral hysteropexy for apical support, with promising short-term efficacy and safety. However, further studies across multiple sites are needed in evaluating long-term efficacy and safety profile of vNOTES extraperitoneal sacrocolpopexy.

Study Objective This study aimed to describe the new “chopstick technique” in laparoendoscopic single-site radical hysterectomy (LESS-RH) and explore its feasibility, safety and perioperative outcomes in the treatment of early stage cervical cancer. Design Retrospective study. Setting The First Affiliated Hospital of Third Military Medical University, Chongqing, China. Patients or Participants Women with federation international of gynecology and obstetrics (FIGO) stage Ia1 with lymph vascular space invasion or stage Ia2-IIa2 cervical cancer. Interventions “Chopstick technique” was performed in LESS-RH and pelvic lymph node dissection. The demographic characteristics and perioperative efficacy of the patients were summarized and analyzed. Measurements and Main Results LESS-RH was attempted in 84 patients, and 83 (98%) patients underwent the procedure successfully. One patient underwent conversion to traditional laproscopic surgery secondary to phase IV endometriosis. “Chopstick technique” was used in all the 83 cases, wherein 40 cases used the single-incision three-channel laparoscopy platform, and 43 used the multichannel-tipped single port laparoscopy platform (HangT Port). The average operation time was 225.0±50.2min and the median intraoperative blood loss was 100mL. During the operations in the first 20 cases, 2 patients had intraoperative vascular injuries and 1 patient had bladder injury, and all were repaired under LESS. One case had ureterovaginal fistula 14 days after operation, and was successfully repaired by ureteroneocystostomy. The average number of pelvic lymph node dissections was 21, and the pathological examination of incisal edge was negative. Deep stromal invasion in 43 cases, LVSI in 16 cases,positive parametrium in 1 case, positive pelvic nodes in 15 cases. 33 patients were treated with postoperative chemotherapy and radiotherapy and 19 patients with intermediate risk factors were treated with radiotherapy postoperatively. Conclusion “Chopstick technique” under LESS was considered feasible for treating cervical cancer.

Parkinson’s disease (PD) is attributed to interactions among genes and environmental and lifestyle factors, but the genetic architecture of PD is complex and not completely understood. To evaluate whether the genetic profile modifies PD development and cerebrospinal fluid (CSF) pathological biomarkers, we enrolled 418 PD patients and 426 age- and sex-matched normal controls. Forty-six single nucleotide polymorphisms (SNPs) that were reported to be significantly associated with PD in large-scale genome-wide association studies (GWASs) were genotyped and analysed. The alleles associated with PD were used to build polygenic risk score (PRS) models to represent polygenic risk. The Cox proportional hazards model and receiver operating characteristic (ROC) analyses were used to evaluate the prediction value of the PRS for PD risk and age at onset. The CSF α-synuclein levels were measured in a subgroup of control subjects (n = 262), and its relationship with the PRS was analysed. We found that some SNPs identified from other populations had significant correlations with PD in our Chinese cohort. The PRS we built had prediction value for PD risk and age at onset. The CSF α-synuclein level had no correlation with the PRS in normal subjects.

Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Clearance of Aβ is a promising therapeutic strategy for AD. We have previously demonstrated that peripheral organs play important roles in the clearance of brain-derived Aβ. In the present study, we recruited 46 patients with liver cirrhosis and 46 normal controls and found that plasma Aβ40 and Aβ42 levels were significantly higher in the cirrhosis patients than in the normal controls. Notably, cirrhosis patients with hepatitis B virus (HBV) infection had higher plasma Aβ40 and Aβ42 levels than HBV-negative cirrhosis patients. Besides, cirrhosis patients had significantly higher plasma levels of interleukin-1β (IL-1β) and IL-6. Plasma tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) levels were not significantly different between the groups. Moreover, we found significant correlations of hepatic functions with plasma Aβ40 and Aβ42 levels. Plasma IL-6 levels were also significantly correlated with plasma Aβ40 levels. However, in the linear regression model, we found significant correlation of plasma Aβ40 levels with hepatic functions, but not with plasma IL-6 levels. Our results indicate that the hepatic dysfunctions might result in decreased peripheral Aβ clearance by the liver. Protecting hepatic functions might be helpful for the clearance of brain-derived Aβ in the blood.

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by parenchymal and vascular beta-amyloid (Aβ) burden, tau pathology, neuroinflammation, and loss of neurons and synapses. There is a clear sex difference in the prevalence of AD. However, sex differences in AD-type pathologies have not been systematically documented. Applying 12-month-old female and male APP/PS1 mice as a model, we investigated the sex dimorphism in these major pathological indices. Compared with male APP/PS1 mice, the females exhibited higher parenchymal Aβ burdens, with the sex difference in hippocampus being the most significant. Female APP/PS1 mice had more severe cerebral amyloid angiopathy and subsequent microhemorrhage. In addition, female APP/PS1 mice also showed higher levels of phosphorylated tau and proinflammatory cytokines, more severe astrocytosis and microgliosis, and greater neuronal and synaptic degenerations. The present study systematically described a sex dimorphism in AD-type pathologic indices, suggesting that gender should be taken into account in designing studies involving these pathological indices and when interpreting the relevant findings in those studies.

Study Objective To investigate the feasibility and safety of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) for endometrial carcinoma (EC). Design Retrospective study. Setting The First Affiliated Hospital of Third Military Medical University, Chongqing, China Patients or Participants Women with federation international of gynecology and obstetrics (FIGO) stage IA endometrial cancer. Interventions vNOTES surgery consist of hysterectomy, bilateral salpingo- oophorectomy and bilateral pelvic and para-aortic lymph node dissection were performed by by a gynecologic oncologist. Clinicopathologic, surgical, and perioperative outcomes were analyzed. Measurements and Main Results All the 12 patients were successfully operated. Vaginal hysterectomy was performed in five patients, and vNOTES hysterectomy was performed in seven patients. All the 12 cases underwent bilateral salpingo-oophorectomy under vNOTES. Pelvic lymph node dissection was performed in six patients, sentinel lymph node biopsy was performed in four patients, and pelvic lymph node dissection plus para-aortic lymphadenectomy was performed in two patients. The median operative time was 172 minutes (94-235 minutes), the median blood loss was 117 (50-200) ml, and the median postoperative hospital stay was 5 (4-9) days. The median time for postoperative recovery of gastrointestinal function was 21 hours (12-40 hours), the median pain score at postoperative 12 hours was 2 (1-4) and 1 (1-2) at postoperative 24 hours. The median follow-up time was 5 months. The vaginal stump incision healed well in all the patients. Conclusion vNOTES is a safe and effective method for comprehensive surgical staging of EC. Larger studies are needed to confirm whether the increased technical difficulty of this procedure justifies its use in routine gynecologic oncology practice.

Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay. We found a specific reduction of TRPC6 mRNA levels in four AD sets and one MCI set. The median TRPC6 mRNA levels were lower in the following: (1) combined AD patients than in age-matched controls (0.78 vs 1.73, P

Chronic obstructive pulmonary disease (COPD) is associated with cognitive decline, but the molecular link between COPD and dementia or Alzheimer's disease (AD) remains unclear. This study was aimed to investigate whether serum Aβ levels are correlated with COPD. 77 cognitively normal COPD patients and 45 age- and gender-matched normal controls were admitted to the study. Serum Aβ40 and Aβ42 levels were measured using ELISA kits. Serum C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT) measurements were done using standard laboratory methods. Pulmonary function tests were performed to assess the pulmonary function and determine the degree of lung damage. Significantly increased levels of serum Aβ40, Aβ42, and total Aβ levels were found in patients with COPD in comparison with normal controls. In COPD patients, serum Aβ levels were higher in subjects with serum CRP, IL-6, and PCT upper the limit of normal. Moreover, serum Aβ levels were dramatically higher in COPD patients with worse pulmonary function. Our study suggests that cognitively normal COPD patients may undergo AD-related pathological changes, and COPD might facilitate AD-type pathogenesis.

Mounting evidence suggests that ischemic stroke (IS) is associated with Alzheimer's disease (AD). IS and vascular risk factors increase the risk for AD. However, whether AD pathologies exist in IS and the effects of these pathologies on stroke remain unknown. In the present study, we aimed to investigate the alterations of serum Aβ after acute IS (AIS), and its correlations with the neurological deficits, infarction volume, and site after stroke. AIS patients (n = 35) were recruited within 24 h of symptom onset. Age- and gender-matched AD patients (n = 48) and cognitively normal controls (NC, n = 37) were also enrolled. Serum Aβ40 and Aβ42 and the National Institute of Health Stroke Scale Score (NIHSS) were measured on day 1, 3, and 7 after stroke onset. We found that serum Aβ40 and Aβ42 levels were increased at day 1 and reached peak levels at day 3, and decreased to pre-stroke levels at day 7. Serum Aβ40 levels at day 1 were correlated with the NIHSS scores and infarction volume of AIS patients. Serum Aβ42 levels at day 1 were significantly higher in IS patients with dominant gray matter infarction. Serum Aβ40 levels at day 1 were predictive for NIHSS at day 7. Our results indicate that AIS can induce the generation of Aβ in the brain, which may in turn be involved in the pathogenesis of neurological deficits after stroke. Serum Aβ might be predictive for the short-term neurological deficits after AIS.

Amyloid-beta (Aβ) plays a central role in the pathogenesis of Alzheimer's disease (AD), and it is a major therapeutic target for AD. It is proposed that removal of Aβ in blood can facilitate Aβ clearance from the brain, representing a promising therapeutic approach for AD. However, the efficacy and mechanisms for Aβ clearance by peripheral organs and tissues remain largely unknown. In the present study, 47 chronic kidney disease (CKD) patients (16 newly diagnosed patients who had never been dialyzed and 31 patients who were receiving dialysis) and 43 normal controls (NC) were enrolled. We found that serum Aβ levels were significantly higher in CKD patients than NC. CKD patients who were receiving dialysis had lower serum Aβ levels than patients without receiving dialysis, being comparable to NC. Furthermore, serum Aβ levels were correlated with renal functions reflected by estimated glomerular filtration rate (eGFR) and residual GFR (rGFR). Our study suggests that kidney is involved in peripheral clearance of Aβ, and dialysis might be a potential therapeutic approach of Aβ removal.