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.

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.

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:Acupotomy is effective in the treatment of knee osteoarthritis,but its mechanism is not very clear. OBJECTIVE:To observe the effect of acupotomy on the apoptosis of knee chondrocytes in knee osteoarthritis rats based on osteoclast associated receptor(OSCAR)-tumor necrosis factor-associated apoptosis-inducing ligand(TRAIL)-osteoprotetin(OPG)pathway. METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into normal group(n=9),model group(n=9)and acupotomy group(n=9).Rats in the normal group were routinely housed without any treatment.Animal models of knee osteoarthritis were established by knee injection of papain.Acupotomy intervention was performed 1 week after modeling,once a week for a total of three times.Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION:The Lequesne MG behavioral scores of rats in the model group were elevated compared with the normal group(P<0.01),while the Lequesne MG behavioral scores of rats in the acupotomy group were decreased comparedwith the model group(P<0.01).Hematoxylin-eosin staining results showed that compared with the normal group,the cartilage surface of the rat's knee joints in the model group was worn and uneven and the chondrocytes were swollen,ruptured,reduced in number,and arranged disorderly;while the cartilage surface of the rat's knee joints in the acupotomy group was relatively smooth,and the chondrocytes were high in number and arranged in an orderly manner,with the structure basically clear.Immunohistochemical staining results showed that compared with the normal group,the positive expressions of OSCAR and TRAIL were increased in the model group(P<0.01),while the positive expression of OPG was decreased(P<0.01).Compared with the model group,the positive expressions of OSCAR and TRAIL in the acupotomy group were decreased(P<0.01),while the positive expression of OPG was increased(P<0.01).TUNEL staining results showed that compared with the normal group,the number of apoptotic cells in the model group were increased(P<0.01);compared with the model group,the number of apoptotic cells in the acupotomy group decreased(P<0.01).RT-qRCR and western blot results showed that compared with the normal group,the protein expressions of OSCAR,TRAIL and Bax in the model group were increased(P<0.01),and the protein expressions of OPG and Bcl-2 were decreased(P<0.01);compared with the model group,the protein expressions of OSCAR,TRAIL,and Bax in the acupotomy group were decreased(P<0.01),and the protein expressions of OPG and Bcl-2 were increased(P<0.01).To conclude,acupotomy can reduce cartilage injury of the knee joint in rats with knee osteoarthritis,which may be related to the blockage of mitochondrial pathway apoptotic signaling release by the OSCAR-TRAIL-OPG pathway.

As a novel iron-dependent form of cell death, ferroptosis is characterized by the excessive accumulation of phospholipids containing polyunsaturated fatty acids (PUFA) on the cell membrane and peroxidation. Lipid droplets are always in the dynamic transition of generation and decomposition, play a central role in regulating lipid metabolism, and are always in the dynamic transition of generation and decomposition. Lipid droplet metabolism is closely related to the occurrence of ferroptosis and plays an important role in the disease caused by ferroptosis. This review firstly focuses on the lipid droplet metabolism process and its effects on the storage and release of PUFA, and further elucidates the regulatory mechanism and key regulatory proteins of lipid drop metabolism on ferroptosis, in order to reveal the intrinsic relationship between lipid droplets and ferroptosis, and provide a new strategy for disease prevention and treatment.

Objective:To explore the bioaccessibility of the main metal components in welding fume welding fume in simulated lung fluid, and to evaluate the exposure level of each metal component in combination with the EPA inhalation exposure risk assessment model.Methods:In November 2022, the microscopic morphology characteristics of welding fumes were analyzed by scanning electron microscopy, the bioaccessibility of each metal component in lung fluid simulated normal and lung inflammatory states was analyzed by in vitro simulation method, and the exposure level of each metal component was calculated in combination with the EPA inhalation exposure risk assessment model.Results:The main metal components in carbon dioxide gas shielded welding fumes were Fe, Mn, Zn, Ti, Al, Cu, Cr, Cd, Ni and As, and the bioaccessibility in simulated normal lung interstitial fluid was 0.82%-1.84%, 5.07%-9.41%, 4.52%-7.23%, 5.10%-8.67%, 20.48%-29.60%, 5.27%-9.83%, 4.80%-7.56%, 0.07%-1.08%, 6.48%-13.84% and 33.02%-42.81%. The bioaccessibility of the above metal components in the lung fluid under simulated lung inflammation was 14.79%-27.45%, 34.53%-46.11%, 35.31%-59.13%, 16.45%-22.51%, 60.78%-76.51%, 26.58%-34.12%, 15.32%-25.87%, 2.0%-5.7%, 34.77%-43.33% and 71.34%-88.36%, respectively. Compared with the simulated lurg interstitial fluid, the bioaccessibility of metal components in the lung fluid under the simulated inflammatory state was increased, and the difference was statistically significant ( P<0.05). The average daily exposure dose Mn in the two simulated lung fluids exceeded the inhalation reference limit (>50 times), and the average daily exposure dose Ti and Cr in the simulated lung inflammation exceeded the reference limit (>1.3 times) . Conclusion:Attention should be paid to the bioaccessibility characteristics of metal components in the exposure level and hazard assessment of welding fumes.

【Objective】 To analyze the clinical characteristics of serum vitamin K2 in children and its correlation with bone mineral density, so as to provide reference for the prevention of insufficient bone strength in children. 【Methods】 A total of 4 145 children who underwent serum vitamin K2 testing and physical examination at pediatric outpatient clinics of several municipal and county hospitals in Chongqing from January 2020 to March 2023 were retrospectively selected into this study for serum vitamin K2-related analysis.Further 844 school-age children who completed serum 25-(OH)D and lumbar bone densitometry measurements were screened to analyze the correlation between vitamin K2level and bone mineral density 【Results】 The overall serum vitamin K2 deficiency rate was 61.6% (2 553/4 145), and the difference in serum vitamin K2 deficiency rate between different age groups was statistically significant (χ²=39.364, P<0.05).The vitamin K2 level of children was significantly influenced by season and maternal education level (χ²=45.310,9.990, P<0.05).There were significant differences in age (Z=3.416), gender (χ²=9.218) and serum vitamin K2 deficiency rate (χ²=5.826) between normal bone mass development group and insufficient bone mass development group (P<0.05).Multivariate Logistic regression analysis suggested that vitamin K2 deficiency was an independent risk factor for insufficient bone mass development in school-age children (OR=1.37,95%CI:1.03 - 1.83, P=0.030). 【Conclusions】 There is a higher serum vitamin K2 deficiency rate among children, especially infants and school-age children.Decreased bone mineral density in school-age children may be associated with serum vitamin K2 deficiency.

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.

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 analyse the clinical efficacy of low-frequency of midnight-noon ebb-flow acupuncture-opening method(also called Ziwu Liuzhu Acupuncture,referring to the needling method based on acupoints selection according to qi and blood movement following heavenly-stems and earthly-branches cycle)in treating low myopia in children.Methods A retrospective study was conducted to collect the clinical data of 84 cases(168 eyes)of children with low myopia who received treatment at the Outpatient Department of Guangdong Provincial Hospital of Chinese Medicine from January 2021 to December 2022.The children were divided into two groups according to the different treatment protocols:42 cases(84 eyes)treated with acupuncture combined with conventional optometry as the control group,and 42 cases(84 eyes)treated with low-frequency of midnight-noon ebb-flow acupuncture-opening method combined with conventional optometry as the observation group,and the treatment course of both groups was 24 weeks.The changes of refractive error and axial length before and after treatment were observed,and the clinical efficacy in the two groups of children were evaluated.Results(1)After treatment,there being statistically significant differences in the refractive error between the two groups of the children(P＜0.05),and the differential value of the refractive error of the children between the two groups before and after treatment was statistically significant(P＜0.05).(2)After treatment,there being statistically significant differences in the axial length of the children in both groups(P＜0.05).The differential value of axial lengths of the children between the two groups before and after treatment was statistically significant(P＜0.05).(3)The total effective rate of the observation group was 84.52%(71/84),and which of the control group was 63.10%(53/84),the efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The low-frequency of midnight-noon ebb-flow acupuncture-opening method in treating low myopia in children can effectively postpone the degree of myopia,and decrease the growth of the axis,with exact therapeutic effect.