BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P＜0.01)and the entries into open arms(P＜0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P＜0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P＜0.05),but it was significantly decreased in the model intervention group compared with the model control group(P＜0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P＜0.05),while it was markedly decreased in the experimental group compared with the model group(P＜0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P＜0.05)as well as higher in the experimental group than the model group(P＜0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P＜0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective To preliminarily analyze the genotypic and phenotypic characteristics of glucose-6-phosphate dehydrogenase(G6PD)in blood donors and recipients in Dongguan region,as well as the impact of these characteristics on the efficacy of blood transfusion therapy.Methods A total of 351 pairs of blood sam-ples from donors and recipients were collected from the Tenth Affiliated Hospital of Southern Medical Uni-versity/Dongguan People's Hospital between May and November in 2023.These samples were tested for G6PD genotype,G6PD enzyme activity,erythrocyte osmotic fragility,and blood routine parameters.Addition-ally,hemoglobin levels before and after blood transfusion were collected from recipients for statistical analy-sis.Results The carrier rates of G6PD mutant genes among donors and recipients in Dongguan region were 6.84％and 5.83％,respectively.Six mutation sites were identified,with c.1388G＞A,c.1376G＞T,and c.95A＞G accounting for 84.09％of all mutations.A negative correlation was observed between G6PD activi-ty and blood storage duration in wild-type donors.The G6PD activity significantly decreased when blood from healthy donors was transfused into recipients through standard procedures.Recipients carrying c.1388G＞A,c.1376G＞T,c.95A＞G,c.871G＞A,c.1024C＞T mutation sites showed no statistically significant difference in hemoglobin increment after receiving blood from donors carrying c.1388G＞A,c.1376G＞T,c.95A＞G,c.871G＞A,c.1376G＞T/c.1360C＞T,or c.1388G＞A/c.95A＞G mutation sites.In the internal medicine re-strictive transfusion group,recipients who received blood with enzyme activity≥1300 U/L demonstrated a significantly greater increase in hemoglobin levels compared to those transfused with blood with enzyme activ-ity＜1 300 U/L(P=0.042).Conclusion The carrier rates of G6PD mutant genes among donors and recipi-ents in Dongguan region are both above 5.00％,indicating a relatively high carriage rate.The three primary mutation sites,c.1388G＞A,c.1376G＞T,and c.95A＞G,account for over 80.00％of all mutations.No ad-verse effects on treatment efficacy are observed in recipients carrying G6PD mutant genes after receiving blood from donors with G6PD mutant genes.However,in restrictive transfusion practices within internal medicine,recipients receiving blood with low G6PD enzyme activity demonstrate a reduced hemoglobin increase per unit compared to those receiving blood with normal G6PD enzyme activity.

Objective To investigate the clinical efficacy of Xinxuetong Oral Liquid in the treatment of patients with acute coronary syndrome(ACS).Methods A total of 80 patients with ACS of blood stasis syndrome who were hospitalized in Shunde Hospital of Guangzhou University of Chinese Medicine from January 2023 to September 2023 were randomly divided into the treatment group and control group according to random number table method,40 patients in each group.The patients in the two groups were given conventional western medicine treatment including lifestyle guidance,percutaneous coronary intervention(PCI),and conventional western medicine therapy.Additionally,the treatment group was treated with Xinxuetong Oral Liquid.The course of treatment for the two groups covered eight weeks.Before and after treatment the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome score,blood stasis syndrome score,angina pectoris score,blood lipid indicators,carotid ultrasonography indicators,echocardiography indicators,and serum levels of trimethylamine-N-oxide(TMAO),nitric oxide(NO),endothelin 1(ET-1),interleukin 8(IL-8),serine/threonine-protein kinase 1(AKT-1),and vascular endothelial growth factor A(VEGF-A).After treatment,the efficacy on TCM syndrome efficacy and the safety of the regimen in the two groups were evaluated.Results(1)During the trial,there were two cases of loss to follow-up and one case of withdrawal due to pneumonia,and eventually a total of 77 patients completed the full course of treatment,among which 39 patients were in the treatment group and 38 patients were in the control group.(2)After eight weeks of treatment,the total effective rate of the treatment group was 89.74％(35/39),and that of the control group was 63.16％(24/38).The intergroup comparison(tested by chi-square test)showed that the effective rate of TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of TCM symptoms such as chest pain,chest distress,symptom aggravation at night,and palpitation in the two groups,as well as the score of gloomy complexion in the treatment group,were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease of scores of chest distress,symptom aggravation at night,and palpitation in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the blood stasis syndrome score and angina pectoris symptom score of the two groups of patients were significantly decreased compared with those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the serum TMAO,ET-1,IL-8,AKT-1,and VEGF-A levels in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the serum NO level was significantly increased compared with that before treatment(P＜0.01).The decrease of serum TMAO,ET-1,IL-8,and AKT-1,VEGF-A levels and the increase of serum NO level in the treatment group were significantly superior to those of the control group(P＜0.05 or P＜0.01).(6)After treatment,the total cholesterol(TCHO)and low-density lipoprotein cholesterol(LDL-C)levels of the two groups(P＜0.01)and the triglyceride(TG)level of the treatment group(P＜0.05)were decreased significantly compared with those before treatment,while the high-density lipoprotein cholesterol(HDL-C)level of the treatment group was increased significantly compared with that before treatment(P＜0.01).No obvious changes of TG and HDL-C levels before and after treatment were shown in the control group(P＞0.05).The comparison of blood lipid indicators after treatment between groups showed that there were no statistically significant differences(P＞0.05).(7)After treatment,the carotid ultrasonography indicators of carotid intima-media thickness(IMT)and Crouse score of the carotid plaque in the two groups were significantly improved compared with those before treatment(P＜0.01).However,there was no statistical significance in the comparison of the two indicators between the two groups after treatment(P＞0.05).(8)The observation of echocardiography indicators showed that only the post-treatment left ventricular diameter(LVd)of the treatment group was significantly larger than that before treatment(P＜0.05),while no obvious changes of the other echocardiography indicators before and after treatment were shown in the two groups(P＞0.05).The comparison between the groups after treatment also showed no statistically significant differences(P＞0.05).(9)During the treatment,no serious drug-induced adverse reactions or drug-related severe cardiovascular events and complications occurred in the two groups.Conclusion The combination of Xinxuetong Oral Liquid with conventional western medicine treatment exerts certain efficacy and safety on improving the clinical symptoms of patients with ACS of blood stasis syndrome,and its therapeutic mechanism may be related to the improvement of blood lipid levels,inflammatory response,and TMAO level.

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Ferroptosis is a unique regulated form of cell death that is distinct from apoptosis, necrosis, and other well-characterized regulated cell death types, and plays an important role in the occurrence and development of chronic metabolic diseases, including diabetes, hypertension, hyperlipidemia, and non-alcoholic steatohepatitis. Recently, increasing evidence has supported traditional Chinese medicine (TCM) as a new hot spot for the treatment of chronic metabolic diseases by mediating ferroptosis. Unfortunately, few systematic reviews have described the importance of TCM in treating chronic metabolic diseases through the ferroptosis pathway. In the current review, the mechanism of ferroptosis and the roles of ferroptosis in chronic metabolic diseases are summarized. Additionally, this review illustrates that the regulation of ferroptosis by TCM could be an effective approach for treating chronic metabolic diseases based on experimental evidence and clinical application. In summary, this work will improve the understanding of ferroptosis and the ability of TCM to regulate ferroptosis in chronic metabolic diseases, thereby promoting the development and application of natural TCM.

Objective:To estimate the burden of influenza-associated outpatient consultations in China from 2011 to 2021 surveillance years to provide a reference for developing influenza prevention, control strategies, and vaccination policies.Methods:Data on influenza-like illness (ILI) and virological confirmation of sentinel specimens from 2011 to 2021 surveillance years were extracted from China's national sentinel surveillance system. Generalized additive models were fitted to estimate influenza-associated excess ILI outpatient burden, accounting for seasonal baselines and meteorological factors.Results:Influenza was associated with an average of 1.66 (95% CI: 1.51-1.80) excess ILI consultations per 1 000 person-years (py) in China each year from 2011 to 2021 surveillance years. The influenza-associated outpatient burden was similar across different virus types/subtypes. Influenza A(H1N1)pdm09 led to a higher rate of influenza- associated ILI consultations [0.65 (95% CI: 0.53-0.76) per 1 000 py] compared to other types/subtypes. The age groups with the highest burdens were children aged 0-4 years and 5-14 years, with excess outpatient consultation rates of 15.23 (95% CI: 13.73-16.73) per 1 000 py and 13.53 (95% CI: 12.49-14.52) per 1 000 py, respectively. Conclusions:Influenza caused many outpatient consultations in China, particularly among children aged 0-14. Continuous influenza monitoring and disease burden assessment should be conducted, and close attention should be paid to the changing trends of various influenza virus types/subtypes. When formulating vaccination strategies, priority should be given to recommending vaccination for high-risk populations, such as children.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To estimate the burden of influenza-associated outpatient consultations in China from 2011 to 2021 surveillance years to provide a reference for developing influenza prevention, control strategies, and vaccination policies.Methods:Data on influenza-like illness (ILI) and virological confirmation of sentinel specimens from 2011 to 2021 surveillance years were extracted from China's national sentinel surveillance system. Generalized additive models were fitted to estimate influenza-associated excess ILI outpatient burden, accounting for seasonal baselines and meteorological factors.Results:Influenza was associated with an average of 1.66 (95% CI: 1.51-1.80) excess ILI consultations per 1 000 person-years (py) in China each year from 2011 to 2021 surveillance years. The influenza-associated outpatient burden was similar across different virus types/subtypes. Influenza A(H1N1)pdm09 led to a higher rate of influenza- associated ILI consultations [0.65 (95% CI: 0.53-0.76) per 1 000 py] compared to other types/subtypes. The age groups with the highest burdens were children aged 0-4 years and 5-14 years, with excess outpatient consultation rates of 15.23 (95% CI: 13.73-16.73) per 1 000 py and 13.53 (95% CI: 12.49-14.52) per 1 000 py, respectively. Conclusions:Influenza caused many outpatient consultations in China, particularly among children aged 0-14. Continuous influenza monitoring and disease burden assessment should be conducted, and close attention should be paid to the changing trends of various influenza virus types/subtypes. When formulating vaccination strategies, priority should be given to recommending vaccination for high-risk populations, such as children.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.