[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.

[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.

Back to the campus: Lifelong experience of older learners in a university setting.

This study focuses on older participants' experiences of and views on a lifelong learning program at the Hong Kong Polytechnic University in Hong Kong. As many third age adults tend not to have the opportunity to receive tertiary education when they were young, this program aims to fulfil their dream of studying at a university and boost their self-esteem and self-confidence. Using qualitative research methods, this research was conducted after the MiniU program (supported by the Institute of Active Aging of the Hong Kong Polytechnic University). Semi-structured interviews were conducted with 32 participants after the program. While participants had acquired knowledge and experience of university life from the Mini-U program, they also reported concerns and difficulties with participation including difficulties in memorizing course content and financial difficulties. The program has offered a unique opportunity for enhancing participants' interpersonal relationships and wellbeing. The research also further informs the development of creative lifelong learning programs aimed at improving the well-being of older people.

[The timing of pericardial drainage catheter removal and restart of the anticoagulation in patients suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran: Experiences from 20 cases].

Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.

Stillbirths in China: a nationwide survey.

OBJECTIVE: To estimate a stillbirth rate at 24 or more gestational weeks in 2015-2016 and to explore potentially preventable causes in China. DESIGN: A multi-centre cross-sectional study. SETTING: Ninety-six hospitals distributed in 24 (of 34) provinces in China. POPULATION: A total of 75 132 births at 24 completed weeks of gestation or more. METHODS: COX Proportional Hazard Models were performed to examine risk factors for antepartum and intrapartum stillbirths. Population attributable risk percentage was calculated for major risk factors. Correspondence analysis was used to explore region-specific risk factors for stillbirths. MAIN OUTCOME MEASURES: Stillbirth rate and risk factors for stillbirth. RESULTS: A total of 75 132 births including 949 stillbirths were used for the final analysis, giving a weighted stillbirth rate of 13.2 per 1000 births (95% CI 7.9-18.5). Small for gestational age (SGA) and pre-eclampsia/eclampsia increased antepartum stillbirths by 26.2% and 11.7%, respectively. Fetal anomalies increased antepartum and intrapartum stillbirths by 17.9% and 7.4%, respectively. Overall, 31.4% of all stillbirths were potentially preventable. Advanced maternal age, pre-pregnant obesity, chronic hypertension and diabetes mellitus were important risk factors in East China; low education and SGA were major risk factors in Northwest, Southwest, Northeast and South China; and pre-eclampsia/eclampsia and intrapartum complications were significant risk factors in Central China. CONCLUSIONS: The prevalence of stillbirth was 13.2 per 1000 births in China in 2015-2016. Nearly one-third of all stillbirths may be preventable. Strategies based on regional characteristics should be considered to reduce further the burden of stillbirths in China. TWEETABLE ABSTRACT: The stillbirth rate was 13.2 per 1000 births in China in 2015-2016 and nearly one-third of all stillbirths may be preventable.

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.

[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.

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.

Importance of inpatient hypoglycaemia: impact, prediction and prevention.

Hypoglycaemia is a key barrier to achieving euglycaemic control in people who are hospitalized. Inpatient hypoglycaemia has been linked to adverse clinical outcomes, including mortality and longer stay in hospital. A number of studies have applied mathematical tools and statistical models to predict inpatient hypoglycaemia and identify factors that may result in hypoglycaemic events. Several different approaches have been tested to prevent inpatient hypoglycaemia. These can be categorized as human intervention, computerized methods or application of medical devices. In this review we provide an overview of the epidemiology of inpatient hypoglycaemia and its impact on patients and hospitals. We also discuss the existing methodology used to predict inpatient hypoglycaemia and the limited number of trials performed to prevent inpatient hypoglycaemia. The review highlights the urgent need for evidence-based methods to reduce inpatient hypoglycaemia.

[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.

[Clinical characteristics of left atrial appendage thrombus in patients with hypertrophic cardiomyopathy and non-valvular atrial fibrillation].

Objective: To investigate the incidence and clinical characteristics of left atrial appendage (LAA) thrombus in patients with hypertrophic cardiomyopathy (HCM) and non-valvular atrial fibrillation (AF) . Methods: Data from 10 440 patients with AF who had undergone transesophageal echocardiography (TEE) before cardioversion or catheter ablation at Beijing Anzhen Hospital from April 2006 to December 2018 were retrospectively screened. Two hundred and five HCM patients were included, 820 AF patients with the same CHA(2)DS(2)-VASc score over the same period were selected as the control group. HCM patients were divided into two subgroups based on presence or absence of LAA thrombus/sludge. The baseline of clinical information, transthoracic echocardiographic and TEE measures were compared among all the groups. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of left atrial diameter (LAD) for LAA thrombus/sludge. Multivariate logistic regression analysis was applied to analyze the correlative factors of LAA thrombus/sludge in HCM patients. Results: The incidences of LAA thrombus or sludge were higher in HCM group than in control group (10.7% (22/205) vs. 0.7% (6/820); 8.8% (18/205) vs.7.0% (57/820), P<0.001) . In HCM patients, LAD was significantly larger in LAA thrombus/sludge subjects than in those without thrombus/sludge ((48.9±5.1)mm vs. (45.2±6.1) mm, P<0.001). CHA(2)DS(2)-VASc score was similar between the two subgroups ((2.0±1.4) vs. (1.8±1.4), P>0.05). There was no difference in the rate of patients with a CHA(2)DS(2)-VASc scores ≥2 between the subgroups(62.5% (25/40) vs. 57.0% (94/165), P=0.525). The incidences of LAA thrombus in HCM and AF patients with CHA(2)DS(2)-VASc scores of 0, 1 and 2 were 8.8% (3/34) , 9.6% (5/52) , 11.8% (11/119) , respectively; and the rate of LAA sludge were 8.8% (3/52) , 7.7% (4/52) , 9.2% (11/119) , respectively. The cut off value of LAD for the diagnosis of LAA thrombus/sludge was 44.5 mm. Multivariate logistic regression analysis showed that LAD≥44.5 mm (OR=5.134, 95%CI 1.862-14.156, P=0.002) , non-paroxysmal AF (OR=2.782, 95%CI 1.238-6.252, P=0.013) , previous thromboembolism or stroke (OR=1.820, 95%CI 0.774-4.227, P=0.017) were independent determinants of LAA thrombus/sludge. Conclusions: The incidence of LAA thrombus/sludge is higher in patients with HCM and AF than in AF patients without HCM. The CHA(2)DS(2)-VASc score is similar between HCM and AF patients with LAA thrombus/sludge and those without thrombus/sludge. Patients with CHA(2)DS(2)-VASc score 0-1 are also likely to suffer LAA thrombus/sludge. Left atrial enlargement is associated with LAA thrombus/sludge.

[Analysis of factors affecting the noise-induced high frequency hearing loss of male workers in a vehicle manufacturing enterprise].

Objective: To analyze the relationships between the exposure of occupational noise and the occurrence of noise-induced high frequency hearing loss in automobile manufacturing industry. Methods: From June to November 2017, 1579 male workers were selected for exposure to noise hazards in the automobile manufacturing industry in Guangzhou for more than one year (including one year) using the convenient sampling method. According to the hearing test results, 276 people in the high frequency hearing loss group and 1303 in the normal hearing group were surveyed, occupational health tests were conducted, and the noise intensity in the workplace was measured. The cumulative noise exposure (CNE) was calculated. The relationship between shift work and high frequency hearing loss of noise work is analyzed. Results: Compared with the normal hearing group, the noise exposure intensity, age, length of service, marital status, working system, and physical exercise of the high frequency hearing loss group were statistically significant (P<0.05). Through logistic regression analysis, after correcting the effects of organic solvent contact, marital status, and physical exercise, CNE, age, and shift operations (double-shift operations, three-shift operations) are the risk factors for high frequency hearing loss to occur. Conclusion: The risk of hearing loss of workers exposed to noise in the whole vehicle manufacturing industry may be related to CNE, age, and shift work. Two-shift and three-shift work are possible risk factors for noise-induced high frequency hearing loss.

Malectin gene polymorphisms promote cerebral palsy via M2-like macrophage polarization.

The relationship between gene polymorphisms and the pathogenesis of cerebral palsy (CP) is uncovering recently. Here, we suggested that single nucleotide polymorphisms (SNPs) of MLEC gene might take part in the pathogenesis of CP. We genotyped and analyzed 6 SNP positions of MLEC gene in 916 CP patients and 957 healthy people, which are from the Chinese Han population. The results indicated significant associations between the risk of CP and rs10431386 [allele: P-value = .006, odds ratio (OR) = 1.587, 95% confidence interval (CI) = 1.198-1.967] and rs7964786 [allele: P-value = .005, OR = 1.956, 95% CI = 1.238-2.519] SNP positions of MLEC gene. Further investigations revealed that C alleles of rs10431386 and rs7964786 inhibit the expression of MLEC in blood of CP patients and macrophage cell line. in vitro experiments revealed that MLEC promotes M1 to M2 macrophage polarization. The results of in vitro studies suggest that C alleles of rs10431386 and rs7964786 on MLEC promotes CP by inhibiting M1 to M2 macrophage polarization. Generally, this work suggested the contribution of MLEC gene polymorphisms to the pathogenesis of CP.

Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.

Visualisation of insect tracheal systems by lactic acid immersion.

The endeavours to reveal the tracheal system of insects and some arachnids has a long history. The traditional way to observe a tracheal system in an insect body is by utilising the glycerin immersion method. In this study, we developed the lactic acid immersion method, which reveals a more complete tracheal system. By mounting various types of live specimens or body parts directly into lactic acid, multiple intact and complex tracheal systems were clearly visualised. The lactic acid immersion contributed to revealing tracheal systems by penetrating body tissue while reserving enough time for observation before the penetration of the tracheae. Preliminary comparisons were conducted between lactic acid and other mediae, including glycerin. It turned out that lactic acid immersion provides better details and more distinct structures. In our test, the optimal time for observing the tracheal system was 10-25 min after the organism was immersed in lactic acid.

[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.

[Study on the relationship between HIV drug resistance and CD4(+)T cell counts among antiretroviral therapy patients with low viral load].

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4(+)T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4(+)T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4(+)T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4(+)T cell counts <200 cells/µl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95%CI) of CD4 <200 cells/µl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion: Decreased CD4(+)T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.

[Pollution characteristics and health risk assessment of heavy metals in PM(2.5) in Lanzhou].

Objective: To understand the pollution characteristics and assess the pollution health risks of heavy metals in atmospheric PM(2.5) in Lanzhou. Methods: According to the regional characteristics of air pollution and industrial distribution characteristics in Lanzhou, atmospheric PM(2.5) was sampled monthly in Chengguan and Xigu Districts from January, 2015 to December, 2016. Detected the concentration of PM(2.5) and 12 kinds of elements (Sb, Al, As, Be, Cd, Cr, Hg, Pb, Mn, Ni, Se and Tl) by weighing method and inductively coupled plasma mass spectrometry. Enrichment factor and geo-accumulation index were used to describe the pollution characteristics, while health risk assessment was conducted using the recommended United States Environmental Protection Agency (USA EPA) model. The health risks of non-carcinogens were evaluated by non-cancer hazard quotient (HQ), the non-carcinogenic risk was considered to be negligible when HQ<1, HQ>1 meant a health risk. With a single contaminant cancer Risk value to evaluate the health risks of carcinogens, when the Risk value between 10(-6) to10(-4) as an acceptable level. Results: The daily average concentrations of PM(2.5) was 83.0 µg/m(3), 77.0 µg/m(3) in Chengguan and Xigu Districts, respectively, during the sampling periods, and the concentration of PM(2.5) in winter/spring was higher than summer/fall in both districts. The concentration of Al in PM(2.5) was the highest and other elements in descending order: Pb, Mn, As, Sb/Cd, Tl in both districts. Enrichment factor results showed that Al and Mn were mainly affected by natural factors, the rest of five elements were all typical man-made pollution elements and according to geo-accumulation index pollution level of Cd was the strongest in the winter. The results of health risk assessment showed that Mn had the highest non-cancer risks (HQ>1) and affected the health of the children seriously. HQ reached up to 2.44 and 1.79 in Chengguan and Xigu Districts, respectively. Pb, As, Sb, Cd had slight health impact (HQ<1), could be negligible. The cancer risks range of As, Cr were 6.33×10(-6) to 6.46×10(-5) between the acceptable level of risk (10(-6) to 10(-4)), which indicated that As and Cd had potential cancer-risks. Conclusions: The pollution level of atmospheric PM(2.5) and the heavy metals in it was still grim;the non-cancer risks caused by multiple metals on children deserved attention. Although the cancer risks of As and Cd were between the acceptable level of risk, the potential cancer risk still shall not be ignored.

[Effect and related mechanisms of RTA-408 on rat vascular smooth muscle cell calcification induced by advanced glycation end products].

Objective: To investigate the effect and related mechanisms of RTA-408 on rat vascular smooth muscle cells (VSMCs) calcification induced by advanced glycation end products(AGE). Methods: VSMCs were isolated from the aorta of Sprague Dawley rats and cultured in vitro. The fifth generation of VSMCs were randomly divided into 4 groups with random number table including control group(cells were incubated with normal medium for 2 days, then incubated with bovine serum albumin for 5 days),AGE group (cells were incubated with normal medium for 2 days, then incubated with 200 mg/L AGE for 5 days), experimental group(cells were incubated with 100 nmol/L RTA-408 for 2 days,then incubated with 200 mg/L AGE for 5 days),and RTA group(cells were incubated with 100 nmol/L RTA-408 for 2 days,then incubated with bovine serum albumin for 5 days). Cytosolic calciumin VSMC was measured using arsenazo Ⅲ assay. Von Kossa staining was utilized to detect the calcium deposition.The contents of malondialdehyde(MDA) and superoxide dismutase(SOD) in VSMCs were tested by appropriate kits.The protein expressions of osteopontin (OPN), alkaline phosphatase (ALP), nuclear factor E2 related factor 2(Nrf2), and NAD(P)H: quinone oxidoreductase 1(NQO1) were examined using Western blot. Results: (1) Cytosolic calciumconcentration was significantly higher in AGE group than in control group((2.43±0.15) mmol/L vs. (1.23±0.09) mmol/L, P<0.01), which was significantly reduced in experimental group((1.62±0.18) mmol/L,P<0.01 vs. AGE group). (2) Calcium deposition in VSMCs was significantly upregulated in AGE group than in control group(3.64±0.50 vs. 1.00±0.12, P<0.01), and was downregulated in experimental group (1.56±0.37, P<0.01 vs. AGE group). (3) The MDA contents were higher((3.79±0.27) nmol/mg prot vs.(1.99±0.15) nmol/mg prot, P<0.01), while the SOD activities were lower((308.45±14.28) U/mg prot vs. (428.58±11.00) U/mg prot, P<0.01) in AGE group than in control group. The MDA contents were lower((2.37±0.19) nmol/mg prot vs. (3.79±0.27) nmol/mg prot, P<0.01),while the SOD activities were higher((391.03±22.92) U/mg prot vs. (308.45±14.28) U/mg prot, P<0.05)in experimental group compared with AGE group. (4) The relative expressions of OPN and ALP were higher in AGE group than in control group(3.06±0.21 vs. 1.00±0.07, and 2.89±0.29 vs. 1.00±0.10,both P<0.01), both (OPN(1.15±0.12) and ALP(1.45±0.15)) were downregulated in experimental group (both P<0.01 vs. AGE group). (5) The relative protein expressions of Nrf2 and NQO1 in experimental group were higher than AGE group(2.37±0.17 vs. 1.17±0.09, and 3.91±0.18 vs. 1.05±0.08, both P<0.01). Conclusion: Activation of nrf2/NQO1 signaling pathway by RTA-408 can reduce the AGE-induced VSMC calcification through attenuating oxidative injury.

[Performance of interpreting the variants of long QT syndrome according ACMG guidelines by four clinical gene screening agencies from Beijing].

Objective: To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing. Methods: Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency. Results: All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade. Conclusion: The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.