Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To propose an innovative self-supervised learning method for vascular segmentation in computed tomography angiography (CTA) images by integrating feature reconstruction with masked autoencoding. Methods A 3D masked autoencoder-based framework was developed, where in 3D histogram of oriented gradients (HOG) was utilized for multi-scale vascular feature extraction. During pre-training, random masking was applied to local patches of CTA images, and the model was trained to jointly reconstruct original voxels and HOG features of masked regions. The pre-trained model was further fine-tuned on two annotated datasets for clinical-level vessel segmentation. Results Evaluated on two independent datasets (30 labeled CTA images each), our method achieved superior segmentation accuracy to the supervised neural network U-Net (nnU-Net) baseline, with Dice similarity coefficients of 91.2% vs. 89.7% (aorta) and 84.8% vs. 83.2% (coronary arteries). Conclusion The proposed self-supervised model significantly reduces manual annotation costs without compromising segmentation precision, showing substantial potential for enhancing clinical workflows in vascular disease management.

Objective To investigate the feasibility and clinical experience of kidney transplantation from donors with Marfan syndrome (MFS). Methods Clinical data of 2 recipients undergoing kidney transplantation from the same MFS patient were retrospectively analyzed and literature review of 2 cases was conducted. Characteristics and clinical diagnosis and treatment of kidney transplantation from MFS patients were summarized. Results The Remuzzi scores of the left and right donor kidneys of the MFS patient during time-zero biopsy were 1 and 2. No significant difference was observed in the renal arteriole wall compared with other donors of brain death and cardiac death. Two recipients who received kidney transplantation from the MFS patient suffered from postoperative delayed graft function. After short-term hemodialysis, the graft function of the recipients received the left and right kidney began to gradually recover at postoperative 10 d and 20 d. After discharge, serum creatinine level of the recipient received the left kidney was ranged from 80 to 90 μmol/L, whereas that of the recipient received the right kidney kept declining, and the lowest serum creatinine level was 232 μmol/L before the submission date (at postoperative 43 d). Through literature review, two cases successfully undergoing kidney transplantation from the same MFS donor were reported. Both two recipients experienced delayed graft function, and then renal function was restored to normal. Until the publication date, 1 recipient has survived for 6 years, and the other recipient died of de novo cerebrovascular disease at postoperative 2 years. Conclusions MFS patients may serve as an acceptable source of kidney donors. However, the willingness and general conditions of the recipients should be carefully evaluated before kidney transplantation. Intraoperatively, potential risk of tear of renal arterial media should be properly treated. Extensive attention should be paid to the incidence of postoperative complications.

Objective To investigate the prevalence and risk factors of cognitive impairment in the nursing home population in Changning District, Shanghai. Methods In this study, random cluster sampling method was used to select 570 elderly people from 5 nursing homes in Changning District. Multivariate logistic regression was used to analyze the risk factors influencing cognitive function. Results The total prevalence of cognitive impairment in Changning nursing home population was 22.5%. The prevalence rates of ≤80 and >80 age groups were 16.8% and 23.9%, respectively, and the prevalence rates of men and women were 19.2% and 23.9%, respectively. Multivariate analysis showed that age ≥ 80 years old (OR=1.839, 95% CI: 1.045~3.235), no habit of reading book or newspaper (OR=2.087, 95%CI: 1.282~3.398), limitation of daily activity ability (OR=1.577, 95% CI: 1.023~2.431), and having depressive symptoms (OR=2.809, 95% CI: 1.840~4.288) were all influencing factors for cognitive impairment. Conclusion More than one fifth of elderly people in nursing homes in Changning District have symptoms of cognitive impairment. It is necessary to carry out routine cognitive assessment and appropriate cognitive intervention for the nursing home population to reduce the health and economic losses caused by cognitive impairment.

Objective To explore the effect of LINC00115 targeting miR-874-3p on the biological behavior and paclitaxel sensitivity of liver cancer cells.Methods The qRT-PCR was performed to detect the expression levels of LINC00115 and miR-874-3p in liver cancer tissues and cell lines.The si-NC,si-LINC00115,miR-NC,miR-874-3p,pcDNA,pcDNA-LINC00115,anti-miR-NC+si-LINC00115,anti-miR-874-3p+si-LINC00115 were transfected into liver cancer cells MHCC97H respective-ly.CCK-8 method was applied to assess cell viability and IC50 value to paclitaxel.Transwell assay was performed to detect cell migration and invasion.Dual luciferase reporter gene method was used to determine the relationship between LINC00115 and miR-874-3p.Results LINC00115 was highly expressed(P＜0.05),while miR-874-3p was lowly expressed(P＜0.05)in liver cancer tissues and cell lines.After downregulating LINC00115,the cell absorbance(A)value,the IC50 value to paclitaxel,migra-tion and invasion were significantly reduced(all P＜0.05),while miR-874-3p expression was significantly increased(P＜0.05).After upregulating miR-874-3p,the cell A value,IC50 value to paclitaxel,migration and invasion were significantly reduced(all P＜0.05).After upregulating LINC00115,miR-874-3p expression was decreased(P＜0.05).LINC00115 had a direct interaction with miR-874-3p.Downregulating miR-874-3p significantly reduced the effect of low LINC00115 expression on A value,IC50 value to paclitaxel,migration and invasion of liver cancer cells(all P＜0.05).Conclusion Downregulation of LINC00115 inhibits the prolifera-tion,migration and invasion of liver cancer cells to increase paclitaxel sensitivity by promoting miR-874-3p expression.

Objective To investigate the distribution of abnormal karyotypes and their associations with clinical manifestations of the infertile patients in southern Sichuan Province.Methods A total of 4 157 infertile patients who attended the Reproductive Medicine Center of our hospital from July 2018 to June 2021 were included.The chromosome karyotype in peripheral blood was detected by G-banding,and their semen analysis results,uterine development and other clinical data were collected.Results Among the 4 157 patients,chromosomal polymorphisms were found in 239 cases(5.75％),and abnormal karyotypes wee found 137 cases(3.30％).The abnormal karyotypes included 57 cases(41.61％)of sex chromosome aneuploidy,6 cases(4.38％)of Robertsonian transloca-tions,32 cases(23.36％)of balanced translocations,21 cases(15.33％)of chromosomal inversions,9 cases(6.57％)of mosai-cism,8 cases(5.84％)of marker chromosomes,3 cases(2.19％)of sex reversal and 1 case(0.73％)of sex chromosome deletion.In male patients with abnormal karyotypes,91.58％showed abnormal semen parameters,while in those with polymorphic karyotypes,55％had abnormal semen parameters.The patients with Turner syndrome had significantly smaller uterine dimensions(longitudinal,transverse,and anteroposterior)compared to the normal control group(P＜0.01).Conclusion Chromosomal abnormalities should be the important cause of infertility.Conducting karyotype analysis combining with clinical manifestations is crucial examination for the di-agnosis and reproductive guidance of infertile patients.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Objective To investigate the current situation of home environment safety of the elderly in Changning District, identify the risk factors related to the fall of the home environment of the elderly, and take targeted rectification measures, so as to create a safer environment for the elderly. Methods A phased random sampling method was used to select 201 elderly households from 10 streets in Changning District. Community doctors conducted on-the-spot investigation and assessment to collect information, and Epidata3.1 was used to input data and SAS 9.2 was used for statistical analysis. Results The incidence of falls in the past year was 19.90%, and the score of environmental risk factors/the number of environmental risk factors in each family ranged from 0 to 25, with an average of 9 items (standard deviation of 4.71). The results of multivariate logistic regression analysis show that the high level of falling environment (the number of falling risk factors in home environment ≥12) is still an independent risk factor for falls of the elderly, except for the influence of age and the number of drugs taken (OR=3.835, 95% CI:1.718-8.561). Conclusion The environmental risk factors causing falls are common in the home environment of the elderly in the community. It is necessary to focus on improving the home environment, reducing the risk of falls for the elderly, and creating a safe and comfortable home environment for the elderly.

Objective To analyze the efficacy of salmeterol rotticasone combined with tiotropium bromide in the treatment of elderly patients with stable chronic obstructive pulmonary disease(COPD)and its influence on serum procalcitonin(PCT),serum amyloid A(SAA)and albumin-to-fibrinogen ratio(AFR)levels.Methods The elderly patients with stable COPD were divided into control group and treatment group.The control group was treated with salmeterol rotticasone inhalation powder(1 inhalation each time,twice a day),while the treatment group was given tiotropium bromide inhaled powder aerosol treatment(1 inhalation each time once a day)on the basis of the control group.Patients in two groups were treated for 3 months.The clinical efficacy and differences in pulmonary function[forced expiratory volume in one second(FEV1),FEV1/forced vital capacity(FEV1/FVC),peak expiratory flow(PEF)],modified British Medical Research Council respiratory questionnaire(mMRC)score,COPD Assessment Test(CAT)score and serum PCT,SAA and AFR levels were compared;and the safety was evaluated.Results Fifty-two patients and fifty-eight patients were included in treatment group and control group,respectively.After treatment,the total effective rates in treatment group and control group were 90.38％(47 cases/52 cases)and 75.86％(44 cases/58 cases)(P＜0.05).The FEV1 values in treatment group and control group were(1.49±0.33)and(1.36±0.29)L;the FEV1/FVC values were(61.28±10.56)％and(57.41±10.03)％;PEF values were(5.32±0.88)and(4.93±0.75)L·s-1;mMRC scores were(0.99±0.24)and(1.21±0.27)points;the CAT scores were(11.58±3.02)and(14.26±3.71)points;PCT levels were(0.76±0.11)and(0.85±0.18)μg·L-1;SAA levels were(34.59±4.15)and(37.66±5.34)mg·L-1;AFR levels were 5.97±1.12 and 5.53±1.06,respectively.Compared with the control group,the above indexes in the treatment group were statistically significant(all P＜0.05).The main adverse drug reactions in treatment group were dry mouth,constipation and dizziness and nausea,and the main adverse drug reactions in control group were dry mouth,constipation,and dizziness and nausea.The total incidence rates of adverse drug reactions in treatment group and control group were 21.15％(11 cases/52 cases)and 13.79％(8 cases/58 cases)respectively,with no statistical significance(P＞0.05).Conclusion Salmeterol ticasone inhalation powder and tiotropium bromide inhaled powder aerosol can effectively enhance the clinical efficacy of elderly patients with stable COPD,improve the pulmonary function,relieve the body's inflammation,and promote the improvement of disease condition,with good safety.

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.