Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

BACKGROUND: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. RESULTS: Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. CONCLUSION: High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03015311.
Aged ; Humans ; Cardiovascular Diseases ; Blood Pressure/physiology* ; Cholesterol, LDL ; Hypertension ; Cholesterol ; Risk Factors

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

OBJECTIVE: To improve the standard detection method for acetonitrile in workplace air. METHODS: Acetonitrile in the air of workplace was collected by silica gel, eluted with methanol, separated and determined by gas chromatography with flame ionization detection. RESULTS: After the improvement of the method, the linear range of acetonitrile was 1.57-1 574.00 mg/L, and the correlation coefficient was 0.999 98. The detection limit was 0.29 mg/L and the minimum detection concentration was 0.19 mg/m~(3 )(collected sample volume was 1.5 L). The average desorption efficiency was 93.1%-98.9%. The within-run and between-run precision was 2.6%-3.3% and 1.7%-3.6%, respectively. The samples could be stored at room temperature for at least 10 days. CONCLUSION: The improved method is precisied, accurate and simple to operate, which is suitable for determination of acetonitrile in workplace air.

Objective To explore the effects of systematic nursing intervention on calcium and phosphorus metabolism and pruritus in hemodialysis patients. Methods A total of 60 patients undergoing hemodialysis in the Department of Nephrology at Wuxi Second Hospital Affiliated to Nanjing Medical University from February to August 2017 were selected and divided into control group and observation group by random number method, with 30 cases in each group. The control group was given routine care. Dietary guidance, psychological care and comprehensive health education were implemented in the observation group on the basis of routine nursing. Diet, skin pruritus and calcium and phosphorus metabolism were compared between the two groups. Results The dietary compliance rate in the observation group (83.33%) was higher than that in the control group (60.00%) after the intervention, and the difference was statistically significant (P＜0.05). There was no significant difference in serum calcium levels between the two groups (P＞0.05). The differences in the total parathyroid hormone and serum phosphorus levels between the two groups were statistically significant (P＜ 0.05). The degree of pruritus, the distribution of the skin and the score of sleep disturbance in the observation group were significantly lower than those in the control group, with statistical difference (P＜0.05). Conclusions Systematic nursing plays a positive role in calcium and phosphorus metabolism and pruritus in hemodialysis patients and is worthy of promotion and application.

Objective To compare the clinical efficacy of double-lumen tube intubation between McGrath-5 video-laryngoscope and McCoy laryngoscope in patients with difficult airway. Methods Sixty patients who were predicted as difficult double-lumen tube intubation were divided into two groups using random number table method:McGrath-5 video-laryngoscope group (group A, n = 30) and McCoy laryngoscope group (group B, n = 30). All patients were intubated by two laryngoscopes correspondingly after conventional induction. The success rate of the first intubation, intubation time, the ratio of right positioning, the number of SpO2 < 90% within intubation time, the number of pressing the cricoid, the incidence of intubation complications and hemodynamic parameters [The changes in systolic pressure and heart rate and BIS were recorded before induction (T0), glottic exposure upon laryngoscope insertion (T1), immediately after intubation (T2), 3 min (T3) after intubation]. Results The number of pressing the cricoid was smaller in group A than in group B (P < 0.05), whereas the intubation time in group A was significantly higher than that in group B (P < 0.05). The systolic pressure and heart rate at T3 were dramatically reduced compared with those measured at T0 in both groups (P < 0.05). The systolic pressure and heart rate at T1 and T2 in group A were considerably lower in group A than those in group B (P < 0.05). Conclusions Compared with the McCoy laryngoscope, double-lumen tube intubation by McGrath-5 video-laryngoscope can less impact on hemodynamics, less intubation complications, intubation time although prolonged but not for influence the patient's oxygen supply, for difficult airway double-lumen tube intubation provides a good choice.

OBJECTIVETo explore the influence of genetic and environmental factors on the executive function of twin children.

METHODSThe executive function of 122 twin pairs from Chongqing (aged from 6 to 18 years) were investigated with the perseverative errors of the Wisconsin Card Sorting Test. Structural equation modeling was performed to evaluate the effects of the additive genetic factors (A), dominance genetic latent factors (D) and individual specific environmental factors (E) on the executive functions.

RESULTSThe effects of D and E on perseverative errors were 0. 77 (95%CI: 0.65-0.84) and 0.23 (95%CI: 0.16-0.35), respectively. The probability of perseverative errors showed a significant negative correlation with family functioning and with the total GHQ-12 scores of the fathers and mothers (r:-0.335, -0.335, and -0.219, respectively, P<0.01). Perseverative errors were not significantly correlated with the parenting styles and stress life events.

CONCLUSIONPerseverative errors are influenced by a common dominance genetic latent factor and individual specific environmental factors, but the role of environmental factors such as family functioning and parental health can not be ignored.

Objective Using twins methods to explore the influence of genetic and environmental factor on Intelligence develop-ment of children and adolescent twins .Methods It was 190 pair of twins aged 6 to 18 who lived in Chongqing were recruited ,DNA were extracted from buccal mucosa and venous blood samples to identify zygosity .The intelligence was investigated by using the Wechsler Intelligence Scale for Children(C-WISC) ,the intrapair correlation coefficients of twins were compared and calculate the genetic degrees .Results The total IQ of children aged 6 to 18 heritability were 0 .63 ,Verbal IQ were 0 .44 ,Performance IQ were 0 .57 .The total IQ heritability of children aged 10 to 14 and 15 to 18 years(0 .78 ,0 .79) were higher than that of those aged from 6 to 9 years(0 .018) .Conclusion This study suggested the intelligence of children aged 6 to 18 affected by genetic and environment , and the older ,the more influence of genetic on intelligence development .

Objective To explore the influence of genetic and environmental factors on emotional and behavioral problems in children and adolescents using twins quantitative method. Methods One hundred fifty-six twins pairs, aged from 6 to 18, were included in the present study. The parental version of the strengths and difficulties questionnaire (SDQ)was used to evaluate their emotional and behavioral problems. The DNA test of twin zygosity was conducted using DNA extracted from buccal mucosa or venous blood samples. The influence of genetic and environmental factors on emo-tional and behavioral problems was analyzed using structural equation modeling(SEM). Results Shared environment and special environment had impact on emotional symptoms and their contribution to the total variance of emotional symp- tom was 0.42 and 0.58, respectively. Prosocial behavior was mainly affected by shared environment and the contribution of shared environment to the total variance of prosocial behavior was 0.89. Genetic factors had greater influence on hyperac-tivity/attention deficit and the contribution of genetic factors to the total variance was 0.62. Shared environment had more influence on conduct disorder and the contribution of shared environment to total variance was 0.56. Heredity, shared envi-ronment and special environment had impact on peer problems and their contribution to the total variance was 0.24, 0.33 and 0.43, respectively. Conclusion In child and adolescent period, emotional symptoms are only affected by environ-ment, while behavior problems are affected by the combination of heredity and environment. Different behavior problems are affected by different genetic and environmental factors.