[Jiaotaiwan improves brain glucose metabolism in a mouse model of Alzheimer's disease by activating the PI3K/AKT signaling pathway].

OBJECTIVE: To investigate the effect of Jiaotaiwan on brain insulin-PI3K/AKT pathway in a mouse model of Alzheimer's disease (AD). METHODS: Fifty 3-month-old male APP/PS1 double transgenic mice were randomized into AD model group, low-, medium- and high-dose Jiaotaiwan treatment groups, and donepezil treatment group. Cognitive functions of the mice were assessed using water maze and open field tests, and neuronal pathologies were observed with HE staining and Nissl staining; immunohistochemistry was used to detect amyloid Aß deposition in the brain. Fasting serum insulin levels of the mice were measured, and the expressions of Aß42, insulin-PI3K/AKT pathway components and downstream glucose transporters in the brain tissue were detected with RT-qPCR and Western blotting. RESULTS: The AD mouse models exhibited obvious impairment of learning and memory abilities, significantly reduced hippocampal neurons, and obvious Aß amyloid plaques in the brain tissue with increased Aß42 protein expression (P < 0.05) and insulin resistance index, decreased hippocampal PI3K expressions, lowered expressions of AKT and InR, reduced expressions of GLUT1, GLUT3, and GLUT4, and increased expression of GSK3ß in both the hippocampus and cortex. Treatment with Jiaotaiwan and donepezil both effectively improved memory ability of the mouse models, increased the number of hippocampal neurons, reduced Aß amyloid plaques and increased the expressions of PI3K, AKT, InR, GLUT1, GLUT3 and GLUT4 in the hippocampus and cortex. CONCLUSION: Jiaotaiwan improves learning and memory abilities of APP/PS1 double transgenic mice and delay the development of AD by activating the PI3K/AKT pathway and regulating the expression levels of its downstream GLUTs in the brain.

[The effect of the AIM2 inflammasome in noise-induced cognitive dysfunction in rats].

Objective: To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats. Methods: In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1ß (IL-1ß) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining. Results: Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] (P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) (P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1ß and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) (P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant (P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups (P<0.05) . Conclusion: Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

Clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumor.

OBJECTIVE: Brainstem tumors present a significant challenge in surgical treatment, and the prognostic factors in children are lacking. This study aimed to investigate clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumors. PATIENTS AND METHODS: 50 children with brainstem tumors who underwent surgical treatment, including frameless- or frame-based stereotactic biopsy and resection, were included and followed up for clinical and biological analysis. Factors of outcomes were assessed by univariate and multivariate analysis. RESULTS: 27 cases (54.0%) underwent resection in all children with brainstem tumors. The rate of resection reached as high as 81.8% in children with non-diffuse intrinsic pontine glioma (DIPG), while in children with DIPG, biopsy was performed in the majority, and resection was obtained in the minority with focal necrosis. A rare complication was found following the surgery. Multivariate analysis considered World Health Organization (WHO) grade 3-4, with hazard ratio (HR)=4.48, 95% confidence interval (CI) of 2.84-8.69, p=0.001, H3K27M mutation (HR=2.50, 95% CI 1.73-5.69, p=0.015), and hydrocephalus (HR=2.17, 95% CI 1.08-5.32, p=0.014) as independent adverse prognostic factors. For Kaplan-Meier analysis, children with WHO grade 3-4, Ki-67 LI ≥ 20%, TP53 mutation, H3K27M mutation, DIPG, and hydrocephalus had significantly decreased overall survival (OS). CONCLUSIONS: A high rate of resection has been obtained in non-DIPG, and surgical intervention is remarkably safe and efficient for children with brainstem tumors. WHO grade 3-4, H3K27M mutation, and hydrocephalus indicate poor prognosis in children with brainstem tumors.

[Comparison of efficacy and safety of transurethral thulium laser vapoenucleation of prostate and transurethral thulium laser enucleation of prostate in the treatment of benign prostatic hyperplasia].

Objective: To compare early outcomes between transurethral thulium laser vapoenucleation of prostate and transurethral thulium laser enucleation of prostate for the treatment of benign prostatic hyperplasia (BPH). Methods: Retrospective analysis was conducted on the clinical data of 1 638 BPH patients admitted to the Department of Urology of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to December 2021. There were 916 patients underwent transurethral thulium laser vapoenucleation of prostate (ThuVEP group) and 722 patients underwent transurethral thulium laser enucleation of prostate (ThuLEP group). The operation time, eliminated tissue weight, surgical complications, duration of post-operative catheter implantation were compared between the two groups. The improvement of International Prostate Symptom Score (IPSS), Quality of Life Index (QoL), maximum uroflow rate (Qmax) and post-void residual urine volume (PVR) at 1 month after operation was compared between the two groups. Results: There were no significant differences in age, preoperative and 1-month postoperative prostate volume, IPSS score, QoL score, Qmax, and PVR between the ThuVEP and ThuLEP group (all P>0.05). There were no significant differences in perioperative indicators such as operation time, cutting or enucleation time, tissue crushing time, tissue weight, hemoglobin change, catheter indwelling time, and postoperative hospital stay between ThuVEP group and ThuLEP group (all P>0.05). The incidence of minor gross hematuria after extubation in the ThuVEP group was 7.8% (56/916), which was lower than 9.4% (65/722) in the ThuLEP group (P=0.026); the incidence of temporary incontinence at 1 month after surgery was 5.2% (38/916) in ThuVEP group, lower than 11.9% (86/722) in ThuLEP group (P<0.001). A total of 3 patients (0.4%) in ThuLEP group required operative intervention for severe post-operation bleeding, but none of ThuVEP group suffered from this kind of surgical complications. Conclusions: ThuVEP has similar efficacy with ThuLEP for the treatment of BPH. ThuVEP can significantly reduce the incidence of post-operation temporary urine incontinence, and has much superiority in stanching bleeding.

[Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway].

OBJECTIVE: To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. METHODS: Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. RESULTS: Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). CONCLUSION: BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

[Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant].

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

[A prospective cohort study on the association between grip strength and cognitive function in adults aged 50 years and above].

Objective: To evaluate the association between grip strength (GS) and cognitive function in a population-based longitudinal cohort of Chinese adults aged ≥50 years. Methods: The study population of 3 600 adults was from the baseline survey and two rounds of follow up of World Health Organization (WHO) study of global ageing and adult health (SAGE) in five districts of Shanghai (Hongkou, Huangpu, Minhang, Qingpu and Pudong) after excluding individuals with self-report stroke and depression. The effects of baseline GS on cognitive function and its changes were evaluated. Factor analysis was applied to generate an overall cognition score based on verbal recall trials, verbal fluency test, forward digit span test and backward digit span test. Linear mixed effects model was used to examine the predictive capability of baseline GS for changes in cognitive function. Results: A total of 3 600 participants aged (61.2±8.1) years at baseline survey were included in this study, including 1 668 (46.3%) men and 1 932 (53.7%) women. The average of baseline GS and total cognitive function score were (28.19±12.18) kg and (58.93±14.56) respectively. Cognitive function score declined significantly during the follow-up, however, the changes were different among different age groups, education level groups and household income groups. After adjusted for age, education level, marital status, household income, co-morbidity of chronic conditions, drinking status, smoking status, physical activity level, vegetable/fruit intakes and BMI, no relationships between the baseline GS and cognitive score at baseline survey and at 1st follow-up were observed, however, compared with lower GS quartile group, there was a significant relationship between higher baseline GS level and better cognitive function at 2nd follow-up. The participants with highest GS quartile had better cognitive performance over time (male: ß=1.938,95%CI:0.644-3.231,P=0.003, female: ß=2.192,95%CI:0.975-3.409,P<0.001 and those aged 50-64 years: ß=1.652,95%CI:0.646-2.659,P=0.001) than those with the lowest quartile. Conclusions: Higher baseline GS was significantly related to better cognitive function with slow decline. Thus, it is an indicator of cognitive function in middle-aged and elderly Chinese.

LncRNA ABHD11-AS1 promotes tumor progression in papillary thyroid carcinoma by regulating EPS15L1/EGFR signaling pathway.

OBJECTIVES: lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11-AS1 could be helpful in therapeutic targeting for PTC treatment. METHODS: Differentially expressed lncRNAs were selected from TCGA database. qRT-PCR analysis was applied to examine the expression of ABHD11-AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan-Meier analysis. Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo. RESULTS: High expression of ABHD11-AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated. CONCLUSION: ABHD11-AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.

A novel approach quantifying the periorbital morphology: A comparison of direct, 2-dimensional, and 3-dimensional technologies.

BACKGROUND: The measurement of anatomical structures is critical in plastic and reconstructive surgery. However, few detailed and standardized measurements have been widely used in the periorbital region. This study aimed to evaluate the feasibility of a novel detailed and standardized protocol with 2D and 3D technologies, and explore the relationship between them and direct measurements. METHODS: Fifty healthy Caucasians (100 eyes) between 20 and 68 years old were recruited and captured for 3D photographs by VECTRA M3 3D Imaging System. Subsequently, 24 landmarks were located on each 3D photographs following a standardized protocol, and then 19 linear and 3 angular periorbital variables were measured. Furthermore, two-dimensional (2D) and direct measurements were conducted on each subject and compared with 3D measurements and one another. RESULTS: The grand r means across all measurements were 0.77, 0.78, and 0.88 for direct vs. 2D values, direct vs. 3D values, and 3D vs. 2D values, respectively. The mean absolute differences were 1 mm (ranging from 0.2 mm to 3.7 mm) between direct and 3D measurements, 1 mm (ranging from 0.04 mm to 2.4 mm) between direct and 2D measurements, and 1 mm and 6.6° (ranging from 0.04 mm or 0.5° to 3 mm or 12.8°) between 2D and 3D measurements. CONCLUSIONS: This study verified the feasibility of this detailed and standardized landmark localization protocol for assessing the periorbital morphology with 2D and 3D technologies. This protocol may work as a bridge communicating with all studies involving any of the three technologies in the future.

[Association between grip strength, rapid gait speed and cognition in people aged 50 and above in Shanghai during 2009-2010].

Objective: To investigate the association between grip strength, rapid gait speed and cognition in people aged 50 and above in Shanghai. Methods: Cross-sectional data was collected from the World Health Organization (WHO) study on global ageing and adult health (SAGE) wave 1 (2009-2010). A questionnaire survey was conducted among 8 643 participants aged 50 years old and above selected by using multistage random cluster sampling strategies in Shanghai. Factor analysis was applied to evaluate and generate cognitive function overall score.Association between grip strength, rapid gait speed and cognition was examined by a two-level hierarchical linear model. Results: A total of 8 175 participants were included in this study, who were (62.9±9.7) years old, including 3 782 (46.3%) males. The average grip strength and rapid gait speed of participants were (27.46±12.01) kg and (1.44±0.43) m/s respectively. The average scores of verbal recall (VR), verbal fluency (VF), forward digit span (FDS), backward digit span (BDS) and total cognitive scores were (5.72±0.09), (12.67±0.35), (6.84±0.10), (4.32±0.14) and (60.50±0.95) respectively. Grip strength was positively associated with VR, VF, FDS, BDS and overall cognition (standardized ß=0.036, 0.079, 0.042, 0.046 and 0.043 respectively, P<0.05), and rapid gait speed was also positively associated with VR, VF and overall cognition (standardized ß=0.040, 0.031, 0.039 respectively, P<0.05) after adjusted for age, sex, residence, education level, marital status, household income, co-morbidity of chronic conditions, BMI, drinking, smoking, fruits, vegetables intake and physical activities. Conclusion: Grip strength and rapid gait speed are both positively associated with cognitive function of people aged 50 and above, which would be indicators to evaluate their cognition.

Effect of ulinastatin on interleukins and pulmonary function in bypass patients: a meta-analysis of randomized controlled trials.

BACKGROUND: Our aim was to evaluate the effect of urinary trypsin inhibitors (UTI) on interleukin, tumor necrosis factor-α (TNF-α), and polymorphonuclear neutrophil elastase (PMNE) levels as well as on pulmonary function in patients undergoing cardiopulmonary bypass. MATERIALS AND METHODS: We searched the following databases for relevant studies: PubMed, Medline (Ovid SP), Cochrane Library, Wanfang Data, China Biology Medicine Database, Chinese Periodical Database, China Knowledge Resource Integrated Database, and Chinese Clinical Trial Registry. Two investigators independently collected the data and assessed the quality of each study. RevMan 5.3 was used for the meta-analysis. RESULTS: In total, 15 randomized controlled trials (646 patients) met the inclusion criteria. There was a significant decrease in TNF-α, interleukin-6 (IL-6), IL-8, and PMNE levels at 6 h and 24 h after UTI treatment and an increase in IL-10 levels; additionally, there was a decrease in respiratory index and an improvement in the oxygenation index. Nevertheless, UTI treatment did not affect the length of intensive care unit stay, alveolar-arterial oxygen partial pressure difference, adverse lung events, or hospital mortality. Because of the high heterogeneity of the included trials, the results should be assessed carefully. CONCLUSION: UTI treatment can suppress proinflammatory cytokine elevation and upregulate the release of anti-inflammatory mediators, thereby reducing pulmonary injury and improving pulmonary function after cardiopulmonary bypass.

[The mechanism and role of autologous peritoneum transplantation to enterocystoplasty in porcine model].

Objective: To explore the pathological mechanism and role of autologous peritoneum transplantation onenterocystoplasty in porcine model. Methods: Randomly, four experimental female swine were chosen, and each of their body weight was 28-33 kg. By intravenous anesthesia, the transplantation of autologous peritoneum for bladder reconstruction operation was carried out (to transplant the peritoneum onto an ileum segment of which the mucosa and submucosa had been removed. These flaps were used to mend and augment the bladder by suturing the edge of detective bladders). After removal of ureteral catheters and balloon catheter at day 5 respectively, their voiding behaviors were monitored, and respectively 2 swine were euthanized at week 3/6 for routine pathology, immunohistochemistry, and electron microscopic examinations. Results: Four swine underwent reconstruction, but none died for complications such as peritonitis, ileus and urinary fistula. The length of ileum was 35 cm, and the area of peritoneum was 15 cm×10 cm. Voiding behaviorsof the swine were normal, with clear urine after removal of their catheters. At autopsy, reconstructed bladders were healthy. Pathological examination showed the neobladder had been covered by continuous urothelium while the peritoneum disappeared without ileal mucosa regrowth or residual. Scanning electron microscope showed that the transitional cells of neobladder of swine were complete and orderly, and urothelium around suture border was continuous withoutmalposition. Conclusions: In porcine model, autologous peritoneal transplantation witnessed no immune rejection response for itself, which was replaced by crawling transitional epithelium around anastomosis, rather than by metaplasia.

[Association between edentulism and cognition among people aged 50 and over].

Objective: To investigate the association between edentulism and cognition in people aged 50 and over in China. Methods: Cross-sectional data was collected from the first wave of World Health Organization Study on global AGEing and adult health in China, among people aged 50 and over in China. A comprehensive cognitive test was used to assess cognitive functions, including verbal recall (VR), verbal fluency (VF), forward digit span (FDS) and backward digit span (BDS) among the subjects. Association between edentulism and cognition was examined by a two-level (individual level and community level) linear model. Results: A total of 12 843 individuals aged 50 years and over were included for analysis, with an average age of (63.0±9.3) years. The overall prevalence of edentulism was 11.0%. The edentulous adults had lower mean scores of VR (4.55), VF (10.88), FDS (6.25), BDS (2.96) and overall cognition (49.15) (P<0.001). Edentulism was negatively associated with VR (ß=-0.216, 95%CI: -0.370 - -0.062), FDS (ß=-0.186, 95%CI: -0.293 - -0.078) and overall cognition (ß=-1.703, 95%CI: -3.025 - -0.381) after adjusted for age, sex, residence, education level, marital status, household income, co-morbidity of chronic conditions, BMI, smoking and drinking alcohol. Conclusion: Edentulism was related with lower cognition level in people aged 50 and over in China.

[Association between low handgrip strength and air pollution among people aged 50 years and over].

Objective: To examine the association between long-term exposure to ambient PM(2.5) combined with indoor air pollution and handgrip strength among people aged 50 and over. Methods: Data were from the first wave of World Health Organization Study on global AGEing and adult health in China. Ambient annual concentration of PM(2.5) was estimated by using the satellite data we also investigated the use of fuels and chimneys as indoor air pollution. A two-level (individual level and community level) linear model was applied to examine the association between long-term exposure to ambient PM(2.5) combined with indoor air pollution and the handgrip strength. Results: A total of 13 175 individuals aged 50 years and over were included for analysis. The handgrip strength was (26.67±0.54) kg. Ambient PM(2.5) was found to be significantly associated with the risk of decreased handgrip strength. Outdoor PM(2.5) concentration was negatively correlated with handgrip strength (ß=-0.23, 95%CI: -0.31 - -0.14) decrease in handgrip strength after adjusting for gender, age, residence, education, household assets, intake of vegetables and fruits, smoking and drinking, physical activity. In rural area, compared to those who used solid fuel, use of clean fuel increased (ß=1.41, 95%CI: 0.36-2.46) handgrip strength. But in urban area, we did not find any statistically significant association between the use of clean fuel and handgrip strength (ß=0.19, 95%CI: -0.95-1.32). Conclusion: This study found that long-term exposure to ambient PM(2.5) combined with indoor air pollution was significantly associated with low handgrip strength among people aged 50 years and over, this suggested that ambient PM(2.5) might serve as one of the risk factors for low physical function seen in the people aged 50 years and over.

[Association between frailty and sleep duration among people aged 50 years and over].

Objective: To investigate the association between sleep duration and frailty among people aged 50 years and over. Methods: Cross-sectional data was collected from the first wave of World Health Organization Study on global AGEing and adult health in China. Frailty index was constructed on the proportion of deficits, out of the 40 variables. A two-level (individual level and community level) linear model was performed to identify the related factors on frailty. All the models were stratified by age, gender, residence (urban/rural). Restricted cubic spline was performed to graphically evaluate the dose-response association between self-reported sleep duration and frailty. Results: A total of 13 175 individuals aged 50 years and over participated in this study. Without adjusting on any confounding factors, shorter or longer sleep duration significantly increased the risk of weakness compared with normal sleep time (OR=2.05, 95%CI: 1.71-2.44; OR=1.35, 95%CI: 1.12-1.63). After adjusting for confounding factors such as gender, age, residence, education, family assets, vegetable, smoking, drinking and physical activity, a positive association between short sleep duration and frailty was noticed compared with normal sleep time (aOR=1.60, 95%CI: 1.27-2.01). The results of stratified analysis on sex, age and urban and rural areas showed that, after adjusting for gender, age, residence, education level, family assets, intake of vegetables and fruits, smoking, drinking and physical activity, only shorter sleep duration was positively correlated with the risk of weakness. In addition, among people aged 65 years and over, adjusted for confounding factors, the risk of weakness increased by 91%, compared with normal sleep time (aOR=1.91, 95%CI: 1.46-2.49). The dose-response curve also showed that the sleep duration and frailty present an approximate "U" shaped relationship. Conclusion: Short sleep duration might be associated with frailty.

Intra-articular injection of magnesium chloride attenuates osteoarthritis progression in rats.

OBJECTIVE: To explore the effects of Mg2+ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg2+ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM). DESIGN: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl2 (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450-500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. RESULTS: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg2+in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg2+ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg2+ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg2+ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results. CONCLUSION: Intra-articular injections of Mg2+ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.

[Effect of baseline CD(4)(+) T cell count on drop-out of antiretroviral therapy in HIV infected persons in Guangxi Zhuang Autonomous Region, 2008-2015].

Objective: To investigate the effect of baseline CD(4)(+) T cell count (CD(4)) on drop-out of antiretroviral therapy (ART) in HIV infected persons. Methods: Retrospective cohort was conducted in this study. HIV infected persons aged≥18 years and receiving free ART for the first time in Guangxi Zhuang Autonomous Region (Guangxi) from 2008 to 2015 were selected from the antiretroviral treatment database of National Comprehensive HIV/AIDS Information System, with follow-up conducted till May 30, 2016. Cause-specific Cox proportional hazard models were used to evaluate effect of different CD(4) on the drop-out of ART in the HIV infected persons. Results: A total of 58 502 eligible study participants were included in this retrospective cohort study. The average drop-out ratio was 4.8/100 person-years. After controlling the following baseline covariates: age, sex, marital status, route of HIV infection, WHO clinical stage before ART, initial/current ART regiment, ART regiment adjustment, and year of initiating ART for potential confounding, the adjusted HR of drop-out for HIV infected persons with 200- cells/µl, 351-cells/µl and ≥500 cells/µl were 1.110 (95%CI: 1.053-1.171, P<0.001), 1.391 (95%CI: 1.278-1.514, P<0.001) and 1.695 (95%CI: 1.497-1.918, P<0.001), respectively, in risk for drop-out compared with those with baseline CD(4)<200 cells/µl. Among the HIV infected persons, 56.0% (1 601/2 861) of drug withdrawal was due to poor compliance with medication. Conclusions: With the increase of baseline CD(4) when initiating ART, the risk for the drop-out in HIV infected persons increased significantly. To further reduce the drop-out of ART, it is important to take CD(4) into account in initiating ART and to strengthen the health education on treatment compliancy and training for healthcare providers.

Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats.

Previously, we have demonstrated that human tissue kallikrein 1 (hKLK1) improves age-related erectile dysfunction (ED). Autophagy has been implicated in age-related diseases, including ED. However, the molecular mechanisms underlying hKLK1-mediated amelioration of age-related ED via regulation of autophagy remains unknown. To explore the potential mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring human KLK1 (TGR) were bred till 4 or 18 months of age and divided into three groups: young WTR (yWTR) as the control group, aged WTR (aWTR) group, and aged TGR (aTGR) group. The erectile function of each rat was evaluated using cavernous nerve electrostimulation. The ratio of intracavernous pressure/mean arterial pressure (ICP/MAP) and total ICP were also measured. Western blotting, immunohistochemistry, and transmission electron microscopy were performed to detect the levels of autophagy. The expression levels of related signaling pathways were determined by western blotting and immunohistochemistry. We found that hKLK1 improved the impaired erectile function of aged rats. Compared to the yWTR and aTGR groups, the aWTR group showed reduced smooth muscle/collagen ratio, fewer autophagosomes, and lower expression of Beclin 1 and LC3-II, which indicate impaired smooth muscle function and low level of autophagy in the smooth muscle cells. Moreover, the PI3K/Akt/mTOR signaling pathway, which is considered to be a negative regulator of autophagy, was upregulated in the aWTR group. hKLK1 may partially restore erectile function in aged transgenic rats by upregulating protective autophagy via the PI3K/Akt/mTOR pathway. These observations indicate that hKLK1 is a potential gene therapy candidate for age-related ED.

[The influence of molecular classification of breast cancer on the safety of breast-conserving surgery].

Objective: To analyze the relationship between the breast cancer molecular classification and the prognosis of patients underwent breast-conserving therapy and to discuss the safety of the breast conserving surgery from the choice of operation in terms of breast cancer molecular classification. Methods: Clinical data of 618 patients with breast-conserving therapy in Tianjin Medical University Cancer Institute and Hospital from August 2005 to August 2010 were analyzed retrospectively. According to the molecular classification when breast cancer was diagnosed, patients were subdivided into five groups, including Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative. Clinicopathological characteristics and prognosis were compared among five groups and the influencing factors of local recurrence, distant metastasis and overall survival were analyzed. Results: Among 618 patients, there were 148 cases Luminal A, 231 cases Luminal B1, 63 cases Luminal B2, 40 cases HER-2-positive and 136 cases Triple-negative. The age, family history, TNM stage, calcification, histological grade, pathological type and response to endocrine therapy of these 5 molecular types of breast cancer patients were significantly different (all P<0.05). The 5-year local regional recurrence-free survival rates of Luminal A, Luminal B1, Luminal B2, HER-2-positive and Triple-negative were 99.3%, 98.7%, 98.4%, 94.9% and 95.9%, respectively, without significant differences (P=0.104). The 5-year distant metastasis-free survival rates of these 5 types were 97.3%, 95.7%, 93.7%, 87.5% and 91.4%, respectively, with significant differences (P=0.013). Moreover, the 5-year overall survival rates of these 5 types were 98.6%, 97.8%, 98.4%, 92.5% and 95.6%, respectively, without significant differences (P=0.153). Multifactor analysis showed that radiotherapy (HR=0.036, P=0.049) and the number of lymph node metastases (HR=10.72, P=0.004) were independent factors of local recurrence of breast cancer patients underwent breast-conserving therapy. The age (HR=0.369, P=0.046), status of surgical margin (HR=5.486, P=0.007), number of lymph node metastases (HR=2.882, P=0.023) and molecular typing (HR=5.191, P=0.008) were independent factors of distant metastasis of above breast cancer patients. None of the factors were found to be independent factors of the overall survival of these breast cancer patients. Conclusions: Breast conserving therapy does not increase the risks of local recurrence and death of HER-2-positive and Triple-negative breast cancer patients. Therefore, breast conserving therapy can be accepted by patients with HER-2-positive and Triple-negative breast cancer.