In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

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 report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To investigate the changing trends in etiology and treatment of male urethral stricture in recent 10 years.Methods A total of 940 male patients with urethral stricture admitted to the Department of Urology of Beijing Jishuitan Hospital during Jan.2013 and Dec.2022 were continually collected.The clinical data were divided into two groups according to the time of admission,namely the group from 2013 to 2017 and the group from 2018 to 2022,for a comparative analysis of the previous and subsequent 5 years.The etiology,location,length and the type of treatment of urethral stricture were retrospectively analyzed.Results The causes of the 940 cases of male urethral stricture were trauma in 447(47.55％),iatrogenic injury in 220(23.40％),idiopathic causes in 128(13.62％),lichen sclerosus(LS)in 78(8.30％),infection in 46(4.89％),and other causes in 21(2.23％).The treatment methods were urethroplasty in 691(73.51％),direct vision internal urethrotomy(DVIU)in 122(12.98％),urethral dilatation in 86(9.15％),and suprapubic cystostomy in 41(4.36％).Compared with the previous 5 years,in the past 5 years,the proportion of urethral stricture caused by trauma decreased significantly(60.34％vs.41.71％,P＜0.001),while the proportion of iatrogenic injury increased significantly(17.63％vs.26.05％,P=0.005).In the past 5 years,the proportion of urethroplasty increased from 68.81％to 75.66％(P=0.027),while the proportion of DVIU decreased from 19.66％to 9.92％(P＜0.001).Inthe past 5 years,the proportion of membranous urethral stenosis decreased significantly(26.98％vs.50.85％,x2=51.06,P＜0.001),the proportion of penile urethral stricture(21.40％vs.7.80％,=26.37,P＜0.001)and meatal stenosis(9.30％vs.4.75％,x2=5.80,P＜0.001)increased significantly.Conclusion In the past decade,trauma was the main cause of male urethral strictures,but its proportion showed a decreasing trend.Iatrogenic injury led to a gradual increase in urethral strictures,which was the second leading cause of male urethral stricture.The application of urethroplasty increased significantly,making it the main treatment method for male urethral stricture.

Objective:To investigate the relationship between walking speed, life-space mobility (LSM), cognitive function and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes mellitus in community, and compare the predictive value of walking speed and LSM alone and combined in elderly patients with type 2 diabetes mellitus.Methods:This was a cross-sectional study. Using the convenient sampling method, a total of 448 elderly patients with type 2 diabetes mellitus from three communities in Hefei City were selected as the research objects from September 2022 to May 2023. Daily walking speed was measured using the 4-Meter Walking Speed, LSM was assessed using the Chinese version of Life-Space Assessment (LSA), and cognitive function was evaluated using the Chinese version of Montreal Cognitive Assessment (MoCA). Participants were divided to the MCI group and non-MCI group. Spearman correlation analysis was used to explore the relationships between walking speed, LSM and cognitive function. Logistic regression analysis was used to analyze the relationship between walking speed, LSM and MCI. Area under the curve ( AUC) of receiver operating characteristic (ROC) curve analysis was performed to compare the effects of walking speed and Chinese version LSA score on the prediction of MCI alone and in combination. Results:The walking speed and the Chinese version LSA score were both positively correlated with the Chinese version MoCA score ( r=0.598, 0.543; P<0.05). Chinese version LSA score ( OR=0.942) and walking speed score ( OR=0.490) were influencing factors for MCI in elderly patients with type 2 diabetes mellitus ( P<0.05). The AUC for walking speed in predicting MCI was 0.875, with a cutoff value of 3 points. Chinese version LSA score in predicting MCI had an AUC of 0.887 with a cutoff value of 59 points. When used in combination, they achieved an AUC of 0.915, with cutoff values of 55 points for Chinese version LSA scores and 3 points for walking speed scores. Conclusions:The combination of walking speed and LSM can more accurately predict the occurrence of MCI in elderly patients with type 2 diabetes mellitus than the single application, which provide a reference for improving the cognitive function of elderly patients with type 2 diabetes mellitus.

Objective:To explore the chain mediating effect of self-rated health and aging attitudes on the relationship between life space and psychological distress of community-dwelling older adults.Methods:From August to November 2023, convenience sampling was used to select older adults from three communities of Baohe District in Hefei City as subjects. General Information Questionnaire, Life Space Assessment (LSA), Self-Rated Health (SRH), Attitudes to Aging Questionnaire (AAQ), and 10-item Kessler Psychological Distress Scale (K10) were used for the survey. Spearman correlation was used to analyze the correlation between life space and self-rated health, aging attitudes, and psychological distress. Process macro program of SPSS 25.0 software was used to test for mediating effects.Results:A total of 700 questionnaires were distributed and 669 valid questionnaires were collected, with a valid response rate of 95.57%. Among 669 community-dwelling older adults, the LSA, SRH, AAQ, and K10 scores were (74.35±19.39), (3.23±0.96), (80.66±13.43), and (19.29±6.26), respectively. Spearman correlation analysis showed a positive correlation between life space and attitudes to aging ( rs=0.568, P<0.01) and negative correlations between life space and self-rated health and psychological distress ( rs=-0.334 and -0.455; both P<0.01). The mediating effect test showed that self-rated health and aging attitudes had chain mediating effects on life space and psychological distress, with a mediating effect value of -0.053, accounting for 11.60% of the total effect. Conclusions:Life space can not only directly affect the psychological distress of community-dwelling older adults but also indirectly predict psychological distress through the mediating effect of self-rated health and aging attitudes.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.