ObjectiveTo explore the potential mechanisms of kidney-tonifying and blood-activating acupuncture for Alzheimer's disease. MethodsMale SAMP8 mice were randomly divided into a model group， acupuncture group， non-acupoint group， and donepezi group， with 10 mice in each group， and 10 SAMR1 mice as normal group. The acupuncture group received acupuncture at Baihui （GV 20）， Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17）. Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17） were stimulated on the left side first and then on the right side alternately， once a day. The non-acupoint group received acupuncture at fixed bilateral non-meridian， non-acupoint points under the ribs， once a day. The model and normal groups underwent equivalent handling and restraint stress without acupuncture. The donepezi group received 1 mg/kg donepezil via gastric gavage daily. All groups were treated for 4 weeks. After treatment， Morris water maze tests （to record orientation sailing latency， number of traverses through the platform quadrant） and open field （to record distance travelled） were used to evaluate learning and memory abilities； hippocampal neuronal damage was analyzed via HE and Nissl staining； mitochondrial membrane potential and reactive oxygen species （ROS） were measured using assay kits； Western blot and qRT-PCR were performed to detect silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor gamma coactivator 1-alpha （PGC-1α）， and mRNA expression levels. ResultsCompared with the normal group， mice in the model group and non-acupoint group showed elevated orientation sailing latency and relative multiplicity of ROS in hippocampal tissues， and reduced number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-staining-positive cells in the hippocampal tissues， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1， PGC-1α （P＜0.01）； HE staining showed that the hippocampal tissues of the mice was loosely arranged， with reduced number of neurons and vacuolar degeneration； Nissl staining showed that pyramidal neurons in the hippocampal region were not neatly arranged， and the number of Nissl bodies in the cytoplasm was less and the staining was lighter. Compared with the model group， mice in the acupuncture group and donepezil group had lower orientation sailing latency and relative multiplicity of ROS in the hippocampal tissue， higher number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-stained positive cells in the hippocampal tissue， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1 and PGC-1α （P＜0.01）， and HE staining and Nissl staining showed significant improvement in hippocampal histopathological damage. Compared with the donepezil group， the orientation sailing latency shortened in the acupuncture group of mice （P＜0.01）. ConclusionKidney-tonifying and blood-activating acupuncture method can alleviate the SIRT1/PGC-1α signalling pathway in the hippocampal tissue and improve the mitochondrial function， thus alleviating the neuronal damage， which is one of the possible mechanisms for its treatment of Alzheimer's disease.

Objective: To examine the casual association between age at first sexual intercourse and gynecologic malignant tumors using Mendelian randomization (MR) approach. Methods: The single nucleotide polymorphisms (SNPs) associated with age at first sexual intercourse were obtained from a meta-analysis of genome-wide association study (GWAS), and the SNPs related to gynecologic malignant tumors (ovarian cancer, endometrial cancer, cervical cancer), and their subtypes were sourced from the IEU OpenGWAS database. Using age at first sexual intercourse as the exposure and gynecologic malignant tumors as the outcome, a MR analysis was performed with the inverse-variance weighted (IVW) method. Heterogeneity was assessed using Cochran's Q test, horizontal pleiotropy was evaluated using MR-Egger regression and MR-PRESSO test, and bias was examined using funnel plots. Results: The Mendelian randomization analysis demonstrated that younger age at first sexual intercourse was significantly associated with an increased risk of low-grade serous ovarian carcinoma (OR=0.553, 95%CI: 0.335-0.911), cervical cancer (OR=0.674, 95%CI: 0.466-0.974), endometrial cancer (OR=0.854, 95%CI: 0.730-0.999), and endometrioid carcinoma (OR=0.830, 95%CI: 0.690-0.998). No statistical association was found between the age at first sexual intercourse and ovarian cancer, high-grade serous ovarian cancer, mucinous ovarian cancer, endometrioid ovarian cancer, or non-endometrioid ovarian cancer (all P>0.05). Sensitivity analysis showed no evidence of undetected instrumental variable heterogeneity or horizontal pleiotropy (all P>0.05), and the funnel plot indicated no presence of bias. Conclusion Younger age at first sexual intercourse may be associated with an increased risk of certain gynecologic malignant tumors, highlighting the need to strengthen adolescent sex education.

Background::Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods::Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared.Results::Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%-3.10%), 2.09% (95% CI: 1.76%-2.43%), and 1.25% (95% CI: 0.99%-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29-4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45-0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment.Conclusions::Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P＜0.05,P＜0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P＜0.01,P＜0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P＜0.05,P＜0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P＜0.05,P＜0.01 or P＜0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

Hydrogen sulfide,as a third gas signal molecule and neurotransmitter,can play a neuroprotective role by anti-oxidative stress,anti-inflammatory response,metabolic inhibition and other mechanisms.It is of great significance for the occurrence and development of neurodegenerative diseases including Alzheimer's disease(AD)and Parkinson's disease(PD)mediated by neuroinflammation.This article reviews the research progress of hydrogen sulfide and neuroinflammation and its mediated neurodegenerative diseases,so as to provide new ideas for the treatment of neurodegenerative diseases.

Objective To evaluate the short-term clinical efficacy of unilateral biportal endoscopic(UBE)technique in the treatment of adjacent segment disease after lumbar interbody fusion.Methods The clinical data of 21 patients with adjacent segment disease after lumbar interbody fusion who treated with UBE technique and followed up for more than 3 months in our hospital from March 2020 to January 2023 were retrospectively analyzed.The operation time,decrease value of hemoglobin 1 day before and after operation,drainage volume of the operation area,time of bed rest and complications were recorded.The Japanese Orthopaedic Association(JOA)score was used to evaluate lumbar function 1 day before operation,3 days and 3 months after operation to determine the improvement.The visual analogue scale(VAS)score was used to evaluate the pain 1 day before operation,3 days and 3 months after operation.Results The operation time was 60～175 minutes,with an average of(95.38±18.64)minutes;the decrease value of hemoglobin was 2～6 g/L,with an average of(1.42±0.18)g/L;the time of bed rest was 27～88 hours,with an average of(36.42±15.33)hours;the drainage volume of the operation area was 50～315 mL,with an average of(85.56±15.65)mL;and one case of dural tear occurred during the operation,who was converted to open surgery for repairing dural sac.There was statistically significant difference in VAS score before operation compared with that 3 days and 3 months after operation(P<0.05).There was statistically significant difference in the JOA score before operation compared with that 3 days and 3 months after surgery(P<0.05).Conclusion UBE technique is effective in the treatment of adjacent segment disease after lumbar interbody fusion,with the advantages of small trauma,little bleeding and short time of bed rest.However,patients with the serious adjacent segment degeneration and severe spinal stenosis may have dural tear during operation.Once it occurs,active repair should be performed to avoid cauda equina herniation and necrosis,or switch to open surgery,if necessary.

The purpose of this study was to reveal the resistance mechanism of Mycoplasma bovis from Xizang yaks to macrolide antibiotics and provide theoretical basis for clinical medication.In this study,10 strains of Mycoplasma bovis from Xizang yaks were tested for drug sensitivity to macrolide antibiotics using the micromethod,and sensitive strains were induced to be highly resist-ant in vitro.The results showed that all 10 strains of Mycoplasma bovis exhibited varying degrees of resistance to macrolide antibiotics.However,through methylation enzyme and inactivation en-zyme gene detection and analysis,it was found that there was no methylation enzyme encoded by the methylation enzyme gene and no resistance mechanism mediated by macrolide inactivation en-zymes,indicating that there were no mutations in the target gene loci of the sensitive and resistant strains.However,highly resistant strains in vitro have mutations at the domain Ⅱ,L22,and even L4 target gene loci,indicating that if two or more target gene amino acid loci undergo mutations,highly resistant strains can be produced.After testing with active efflux systems,it was found that there were no active efflux systems using macrolide antibiotics as substrates.It can be seen that the strain of Mycoplasma bovis from Xizang yaks is prone to mutation under the pressure of high con-centrations of macrolides,and there are mutations in two or more target gene amino acid sites,which is prone to produce highly resistant strains.

Objective:To explore the efficacy and prognosis factors of acute myeloid leukemia with a combination therapy of venetoclax.Methods:A retrospective analysis was performed on the clinical data of AML patients treated with a combination therapy of venetoclax from March 2020 to April 2023 in the First Hospital of Lanzhou University.The efficacy,adverse reactions and survival were observed,and the influencing factors were analyzed.Results:A total of 74 AML patients were included in this study,including 43 initially treated AML and 31 relapsed or refractory AML(R/R AML).The median age of 43 initially treated AML patients was 65 years old,the composite complete remission(cCR)rate was 67.4％(29/43),the objective response rate(ORR)was 72.1％(31/43),and the median overall survival(OS)was 17.3 months.The median age of 31 R/R AML patients was 51 years old,with a cCR rate of 38.7％(12/31),an ORR of 58.1％(18/31),and a median OS of 7.1 months.Sex,the blood cell count before VEN,gene mutation and prognosis stratification were related to whether to obtain cCR.Failure to obtain cCR was an independent risk factor for adverse outcomes.Conclusion:A combination therapy of venetoclax is safe and efficacious for AML.Its efficacy and survival are affected by molecular biology,cytogenetics and other factors.

Objective:To explore the correlation between gene mutations and clinical characteristics,prognosis of myelodysplastic syndromes(MDS).Methods:Clinical data of 131 patients with MDS were collected from the First Hospital of Lanzhou University from June 2015 to February 2023,which 19 of them developed into secondary acute myeloid leukemia(sAML)during follow-up time.Second generation sequencing technology was used to detect the mutation types of MDS disease-related genes,drawn gene maps,and analyzed their correlation and prognosis based on the clinical data of patients.Results:The median age of 131 MDS patients was 58(17-86)years old.The ratio of male to female was 1.3:1.A total of 148 gene mutations and 25 types were found in the center.U2AF1 and ASXL1 were often co-mutations with other genes,which were accompanied by 20q-and normal karyotype(NK)respectively.SETBP1 and SRSF2 were more common in patients over 60 years old,while NPM1 and WT1 under 60 years.Older patients had a higher the number of genetic mutations than younger patients.The incidence of SF3B1 and RUNX1 in males was higher than females and DNMT3A in females was higher than males.The number of gene mutations in sAML was higher than MDS(1.8 vs 1.0,P=0.006).The univariate and multivariate analysis showed that IPSS-R prognostic score≥ 3.5,TP53 were adverse factors for poor prognosis in MDS patients.Patients with monoallelic mutation(ma-TP53)and wild-type(wt-TP53)TP53 had OS better than biallelic mutation(bi-TP53)(P=0.003).The OS of MDS patients was better than sAML(P=0.01)and transplant patients was significantly better than non-transplant patients(P=0.036).Conclusion:Gene mutation is closely related to cytogenetic indexes and clinical features(peripheral blood cell count,sex,age).IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

Objective:To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia(APL)and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants.Methods:Based on the morphological characteristics of APL blast cells,a classification system of 14 categories was established to characterize the inter-and intra-individual cellular morphological heterogeneity of patients.The classification system was used for the morphological analysis of 40 APL patients,and the classification results were statistically analyzed with the patients'conventional test indexes and gene variant characteristics to analyze the correlation of different APL blast cell morphological features with conventional test indexes and gene variants.Results:In the FLT3-ITD mutation-positive group,there were significantly fewer cells with regular nuclear shape,hyper granularity,and missing Auer rods(category 1)than in the FLT3 mutation-negative group(P＜0.05).The activated partial thromboplastin(APTT)was significantly longer in the group with regular nucleus compared to the group with irregular nucleus(P＜0.05).In the hypo-granular group,the APTT was also significantly longer compared to the hyper-granular group(P＜0.01),and the proportion of myeloid blast cells was relatively lower(P＜0.05).The peripheral blood white blood cell counts,D-dimer,lactate dehydrogenase and proportion of bone marrow blast cells were significantly higher in the Auer rods(-)group than Auer rods increasing group(all P＜0.05).Conclusion:The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells,which helps to better assess the intra-and inter-individual heterogeneity of APL blast cells,and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.