Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Objective To investigate the health status of workers exposed to noise in a brewery in Beijing and to analyze the relationship between hearing loss and blood pressure. Methods A total of 949 noise-exposed workers in a brewery who participated in occupational health examination were selected as the investigation subjects. A survey was conducted to investigate the pure tone hearing threshold and abnormal blood pressure of the workers with different characteristics, and to analyze the relationship between the two. Results Among the noise-exposed workers, the detection rates of hearing abnormality, hypertension, and increased systolic and diastolic blood pressure were 73.55%, 52.37%, 43.84% and 46.47%, respectively. The detection rates of hearing abnormality, indicators of hypertension, high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average in males were higher than those in females (P < 0.05). Except that there was no statistically significant difference in weighted values of the better ear’s hearing thresholds among different working age groups (P> 0.05), the detection rates of other hearing abnormality, indicators of hypertension, speech frequency hearing threshold abnormality, high frequency hearing threshold abnormality，increased binaural high frequency hearing threshold on average and the weighted value of the better ear's hearing threshold all increased or had an increasing trend with the increase of age or working years (P< 0.05). The detection rates of hypertension in the groups with high frequency hearing threshold abnormality and increased binaural high frequency hearing threshold on average were higher than those in the normal group (P＜0.05). Conclusion The noise-exposed workers in the brewery have hearing impairment, which is related to the occurrence of hypertension. It is recommended to strengthen the publicity and education on noise protection and take protective measures to reduce the occurrence of occupational noise injury.

Objective To estimate the disease burden of silicosis in China from 1990 to 2021 and analyze its changing trend using the data from the Global Burden of Disease Study 2021 (GBD 2021), and to provide evidence for the prevention and control of silicosis. Methods Data on the incidence, prevalence, morbidity and death, mortality and disability-adjusted life year (DALY) of silicosis in China were extracted from the GBD 2021 to analyze the disease burden and age distribution of silicosis. The average annual percentage change (AAPC) was calculated to reflect the temporal trend of various disease burden indicators from 1990 to 2021. The results were then compared with those of the global population. Results In China, prevalent cases of silicosis increased by 116.62% from 79 075 in 1990 to 171 291 in 2021; incident cases of silicosis increased by 75.75% from 13 315 in 1990 to 23 401 in 2021; deaths of silicosis increased by 30.76% from 4 837 in 1990 to 6 326 in 2021; DALYs of silicosis increased by 14.84% from 150,729.65 person-years in 1990 to 173 091.06 person-years in 2021. The age-standardized rate of prevalence, incidence, mortality, DALY, YLL, and YLD of silicosis in China all showed a downward trend. The AAPC (95% CI) was -0.42% (-0.56% ~ -0.29%), -1.02% (-1.16 %~ -0.88%), -2.16% (-2.49% ~ -1.83%), -2.24% (-2.63% ~ -1.84%), -2.45% (-2.76% ~ -2.14%), and -0.42% (-0.54% ~ -0.29%), respectively. From 1990 to 2021, the age-standardized indicators of silicosis in China were all higher than the global level, and the differences were statistically significant (all P <0.05). The proportion of silicosis incident cases in the total incident cases of pneumoconiosis in China increased from 68.49% in 1990 to 78.58% in 2021. Conclusion The age-standardized indicators of silicosis in China showed a downward trend from 1990 to 2021, but the number of prevalent cases, incident cases, and DALYs showed an increasing trend. The age-standardized incident rate of silicosis in China remains at a high level, suggesting that further efforts should be made to prevent and control silicosis.

Objective To evaluate the relationship between ceftazidime-avibactam(CAZ-AVI)blood concentrations and efficacy in critically ill patients and to investigate the factors influencing blood levels.Methods The CAZ-AVI trough concentrations(Cmin)were detected in 29 patients who received CAZ-AVI treatment for at least 48 hours.The clinical materials of the patients were collected together for retrospective analysis.Results The Cmin of ceftazidime(CAZ)and avibactam(AVI)were(50.95±5.17)and(7.52±0.96)mg·L-1 in the effective group and(31.16±7.03)and(5.37±1.32)mg·L-1 in the ineffective group,respectively.The Cmin of CAZ in the effective group was significantly higher than in the ineffective group(P<0.05),and there was no significant difference in AVI Cmin between the two groups(P>0.05).Spearman's correlation analysis showed that CAZ Cmin was positively correlated with clinical efficacy(P<0.05),and no correlation between AVI Cmin and clinical efficacy(P>0.05).The optimal CAZ Cmin threshold was 24.59 mg·L-1.Multiple linear regression analysis showed that age and creatinine clearance was significantly correlated with the Cmin of CAZ,and creatinine clearance was significantly correlated with AVI Cmin(P<0.05).Conclusions The Cmin of CAZ correlates with efficacy,and it may be more beneficial for clinical treatment to keep the concentration of CAZ-AVI always greater than the minimum inhibitory concentration during the dosing interval.The creatinine clearance should be fully considered when optimizing CAZ-AVI dosage in critically ill patients.

Polymyxins are the first-line drugs used in multidrug resistance(MDR)Gram-negative infections.Polymyxin-induced nephrotoxicity is the major dose-limiting factor hindering its clinical use.It has been suggested that the mechanism of polymyxin-associated nephrotoxicity is related to its accumulation in the kidney upon extensive reabsorption from renal proximal tubular cells,and one or more renal transporters may mediate the process that polymyxins enter the renal tubular cells across cytomembrane.This review aimed to describe the roles of renal transporters in polymyxins reabsorption into the renal tubular cells and provide reference for reducing the nephrotoxicity of polymyxin.

2 patients with lateral orbital malignant tumors were treated by tumor resection and autologous pedicled coronoid-temporalis muscle flap repair of the orbital wall defect.The flaps survived well without obvious facial collapse deformity and with good orbital wall func-tion and aesthetic effect,the mouth open pattern,the intra-oral occlusion and the masticatory function were satisfactory.

Objective:To evaluate the effect of surgery under propofol anesthesia during mid-pregnancy on the cognitive function and hippocampal histone deacetylase 2 (HDAC2)-cAMP response element-binding protein (CREB)-N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B)-containing NMDA receptor (NR2B) signaling pathway in the offspring rats.Methods:Thirty healthy Sprague-Dawley rats at 14 days of gestation were divided into 3 groups ( n=10 each) using a random number table method: propofol anesthesia group (P group), surgery under propofol anesthesia group (S group) and control group (C group). In S group, propofol 20 mg/kg was injected via the caudal vein, and then propofol was continuously infused at a rate of 20 mg·kg -1·h -1 to maintain anesthesia for 4 h, and exploratory laparotomy was performed. Group P received no exploratory laparotomy and the other treatments were similar to those previously described in group S. The equal volume of normal saline was given instead in group C. The learning and memory of the offspring rats was assessed using Morris water maze test on postnatal day 30. The expression of HDAC2, phosphorylated CREB (p-CREB), NR2B, brain-derived neurotriphic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) in offspring′s hippocampi was evaluated by Western blot. Apoptosis in hippocampal neurons was detected by TUNEL staining. Results:Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in P and S groups ( P<0.05). Compared with P group, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in S group ( P<0.05). Conclusions:Surgery under propofol anesthesia during mid-pregnancy can decrease the cognitive function of offspring rats, and the mechanism is related to the regulation of HDAC2-CREB-NR2B signaling pathway and the promotion of apoptosis in hippocampal neurons.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

Objective : To identify the factors affecting the adherence to administration of nucleoside/nucleotide analogues among patients with chronic hepatitis B (CHB), so as to provide insights into improving medication adherence among CHB patients. Methods: CHB patients at ages of 18 to 44 years that underwent treatment in Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine from June 2021 to December 2022 were enrolled, and subjects' demographic and clinical characteristics were collected. The medication adherence was evaluated with the Morisky Medication Adherence Scale, and the negative illness perception was evaluated using the simplified Illness Perception Questionnaire, while the social support level was evaluated with the Social Support Scale. In addition, factors affecting the medical adherence were identified using a multivariable logistic regression model among CHB patients. Results: A total of 225 questionnaires were allocated and 210 valid questionnaires were recovered, with an effective recovery rate of 93.33%. The respondents had a mean age of (35.94±8.72) years, and included 119 men (56.67%) and 91 women (43.33%), with a mean total illness perception score of (44.09±12.06) points. Morisky Medication Adherence Scale classified good in 149 cases (70.95%) and poor in 61 cases (29.05%). Multivariable logistic regression analysis identified an educational level of college degree and above (OR=1.676, 95%CI: 1.105-2.910), family monthly per capita income of >5 000 Yuan (OR=2.518, 95%CI: 1.360-5.033), receiving health education pertaining to CHB (OR=3.590, 95%CI: 1.611- 7.932), high or medium level of social support (high: OR=3.202, 95%CI: 1.613-5.870; medium: OR=1.267, 95%CI: 1.085-2.409) as factors improving the medication adherence, and administration of more than 3 types of drugs (OR=0.388, 95%CI: 0.204-0.526) and high illness perception score (OR=0.601, 95%CI: 0.395-0.808) as factors constraining medication adherence among CHB patients. Conclusions The medication adherence are affected by educational level, family monthly per capita income, types of drugs, illness perception score, health education pertaining to CHB and social support level among CHB patients. Individualized intervention strategy is required targeting these influencing factors to improve the medication adherence among CHB patients.

Objective:To investigate the anatomy of rectus femoris muscle flap and the anterolateral thigh muscle flap and their clinical application in reconstruction of large soft tissue defects after the removal of oral malignant tumour.Methods:From December 2006 to June 2009, 8 specimens of Chinese adult cadavers fixed in 10% formaldehyde were dissected to perform anatomy of anterolateral thigh region at the School of Basic Medical Sciences, Kunming Medical University. Anatomical images were analysed using Image-Pro Plus 6.0. Then, a retrospective study was performed on 19 patients who had postoperative defects after oral malignant tumour surgery and the defects were reconstructed with the rectus femoris muscle flap and the anterolateral thigh muscle flap from March 2020 to July 2022 at the Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital, Kunming Medical University. The postoperative defects of the 19 patients ranged from 3.0 cm×6.0 cm to 5.0 cm×10.0 cm. Ten rectus femoris muscle flaps, 8 anterolateral thigh muscle flaps and 1 combined rectus femoris muscle flap and anterolateral thigh muscle flap were used. The muscular flaps sized from 4.0 cm × 8.0 cm to 6.0 cm × 11.0 cm. Regular postoperative outpatient follow-ups were conducted.Results:The lengths of vessels of the harvested rectus femoris muscle flap and anterolateral thigh muscle flap were 63.4 mm± 12.9 mm and 112.5 mm± 19.6 mm, respectively. The starting outer diameters of the lateral circumflex thigh artery, the oblique branch of the lateral circumflex thigh artery and the descending branch of the lateral circumflex thigh artery were 2.92 mm±0.72 mm, 1.88 mm±0.23 mm and 2.29 mm±0.43 mm, respectively. Postoperative follow-up lasted for 7 to 32 months, with 17.5 months in average. Seventeen flaps were completely survived and the rectus femoris muscle flap was completely mucosalised 5 weeks after surgery. However, 2 rectus femoris muscle flaps had necrosis of which one was changed to a tongue flap reconstruction and the other encountered flap necrosis during postoperative radiotherapy and healed after debridement and dressing changes. There was no postoperative complication in the donor sites. Other than the 2 patients, all other 17 patients had satisfactory clinical outcomes.Conclusion:Both of the starting outer diameters and length of vessels of the femoris muscle flap and the anterolateral thigh muscle flap meet the requirements for reconstruction of maxillofacial defects, and both muscular flaps are simple to prepare, in good reconstructive results with few complication, as well as an excellent outcome. They are feasible approaches for reconstruction of large soft tissue defects left after the removal of an oral malignant tumour.