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.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Objective To determine the application effect of esketamine pretreatment in laparoscopic high ligation of hernia sac in children.Methods A total of 70 children who received laparoscopic high ligation of hernia sac under general anesthesia were selected and divided into the control group and the observation group according to the random number table method,with 35 cases in each group.The control group received conventional general anesthesia,while the observation group was intravenously injected with 0.5 mg/kg of esketamine 15 minutes before the induction of general anesthesia.The preoperative anxiety score,respiratory mechanics indexes,lung injury status,anesthesia recovery,and adverse reactions during the awakening period were compared between the two groups.Results The anxiety scores of the observation group 10 minutes before anesthesia and immediately before anesthesia were significantly lower than those of the control group(P<0.05).The peak airway pressure and mean airway pressure of the observation group 30 minutes after establishing pneumoperitoneum and at the end of the operation were significantly lower than those of the control group(P<0.05).The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)at the end of the operation in the observation group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the time of spontaneous breathing recovery,time to regain consciousness,tracheal extubation time,or post-anesthesia care unit(PACU)stay time between the two groups(P>0.05).The incidence of adverse reactions during the anesthetic awakening period in the observation group was significantly lower than that in the control group(P<0.05).Conclusion Esketamine pretreatment can significantly alleviate preoperative separation anxiety for children undergoing laparoscopic high ligation of hernia sac,reduce lung injury,and decrease airway pressure,which is beneficial to lung protection and postoperative anesthetic recovery,and has few adverse reactions.

Objective To investigate the risk factors for acute respiratory failure in immunocompromised patients with Pneumocystis jirovecii pneumonia(PJP).Methods Clinical data of 123 immunocompromised patients complicated with PJP hospitalized at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2021 to December 2023 were retrospectively collected and analyzed.SPSS 22.0 statistical software package was used to perform multivariate binary logistic regression analysis to identify risk factors for acute respiratory failure in PJP patients.Results Among the 123 PJP patients,77 were HIV-positive,and 46 were HIV-negative.HIV-negative PJP patients were more likely to have comorbidities such as hypertension(P＜0.001),diabetes mellitus(P＜0.001),coronary heart disease(P=0.034),chronic kidney disease(P＜0.001),chronic liver disease(P=0.019),chronic lung disease(P=0.011),and malignant tumor(P＜0.001).They were also more prone to respiratory failure(P＜0.001)and ICU admission(P＜0.001).The HIV-positive patients had significantly lower CD4+T lymphocyte counts and albumin levels(P＜0.001).Forty patients developed acute respiratory failure,and six patients died.Multivariate analysis showed that high neutrophil-to-lymphocyte ratio(NLR)(P=0.031),non-HIV infection(P=0.002),and concomitant infections with other pathogens(P＜0.001)were independent risk factors for incidence of respiratory failure.ROC curve analysis revealed that the area under the curve(AUC)was 0.686(0.584,0.789)for non-HIV infection,0.731(0.637,0.826)for concomitant infections with other pathogens,0.648(0.546,0.750)for NLR.The predicted probability was 0.845(0.778,0.912).Conclusions Non-HIV infection,high NLR,and concomitant infections with other pathogens are independent risk factors for incidence of respiratory failure in PJP patients.The panel combining these factors provides a higher predictive value for respiratory failure.Timely assessment of patient condition and early treatment are vital for better outcomes.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Objective To investigate the risk factors for acute respiratory failure in immunocompromised patients with Pneumocystis jirovecii pneumonia(PJP).Methods Clinical data of 123 immunocompromised patients complicated with PJP hospitalized at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2021 to December 2023 were retrospectively collected and analyzed.SPSS 22.0 statistical software package was used to perform multivariate binary logistic regression analysis to identify risk factors for acute respiratory failure in PJP patients.Results Among the 123 PJP patients,77 were HIV-positive,and 46 were HIV-negative.HIV-negative PJP patients were more likely to have comorbidities such as hypertension(P＜0.001),diabetes mellitus(P＜0.001),coronary heart disease(P=0.034),chronic kidney disease(P＜0.001),chronic liver disease(P=0.019),chronic lung disease(P=0.011),and malignant tumor(P＜0.001).They were also more prone to respiratory failure(P＜0.001)and ICU admission(P＜0.001).The HIV-positive patients had significantly lower CD4+T lymphocyte counts and albumin levels(P＜0.001).Forty patients developed acute respiratory failure,and six patients died.Multivariate analysis showed that high neutrophil-to-lymphocyte ratio(NLR)(P=0.031),non-HIV infection(P=0.002),and concomitant infections with other pathogens(P＜0.001)were independent risk factors for incidence of respiratory failure.ROC curve analysis revealed that the area under the curve(AUC)was 0.686(0.584,0.789)for non-HIV infection,0.731(0.637,0.826)for concomitant infections with other pathogens,0.648(0.546,0.750)for NLR.The predicted probability was 0.845(0.778,0.912).Conclusions Non-HIV infection,high NLR,and concomitant infections with other pathogens are independent risk factors for incidence of respiratory failure in PJP patients.The panel combining these factors provides a higher predictive value for respiratory failure.Timely assessment of patient condition and early treatment are vital for better outcomes.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Objective To determine the application effect of esketamine pretreatment in laparoscopic high ligation of hernia sac in children.Methods A total of 70 children who received laparoscopic high ligation of hernia sac under general anesthesia were selected and divided into the control group and the observation group according to the random number table method,with 35 cases in each group.The control group received conventional general anesthesia,while the observation group was intravenously injected with 0.5 mg/kg of esketamine 15 minutes before the induction of general anesthesia.The preoperative anxiety score,respiratory mechanics indexes,lung injury status,anesthesia recovery,and adverse reactions during the awakening period were compared between the two groups.Results The anxiety scores of the observation group 10 minutes before anesthesia and immediately before anesthesia were significantly lower than those of the control group(P<0.05).The peak airway pressure and mean airway pressure of the observation group 30 minutes after establishing pneumoperitoneum and at the end of the operation were significantly lower than those of the control group(P<0.05).The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)at the end of the operation in the observation group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the time of spontaneous breathing recovery,time to regain consciousness,tracheal extubation time,or post-anesthesia care unit(PACU)stay time between the two groups(P>0.05).The incidence of adverse reactions during the anesthetic awakening period in the observation group was significantly lower than that in the control group(P<0.05).Conclusion Esketamine pretreatment can significantly alleviate preoperative separation anxiety for children undergoing laparoscopic high ligation of hernia sac,reduce lung injury,and decrease airway pressure,which is beneficial to lung protection and postoperative anesthetic recovery,and has few adverse reactions.