Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

Objective To establish a molecular method for the identification of Aucklandia lappa Decne.and its common adulterants,Inula helenium L.,based on tetra-primer amplification refractory mutation system(ARMS).Methods After the analysis and comparison of internal transcribed spacer 2(ITS2)sequence differences between Aucklandia lappa Decne.and Inula helenium L.,single-nucleotide polymorphism(SNP)sites were found to design specific primers for identification,the ARMS method was established to specifically amplify samples from different sources,and identification was carried out according to the size of specific amplification bands.Results The results showed that 170 bp and 271 bp specific bands could be amplified by Aucklandia lappa Decne.and Inula helenium L.,respectively,under the following conditions:annealing temperature 56℃,cycle number 25,primer concentration ratio of internal and external primers 1∶4,agarose gel concentration 1.5%and using 2×TSINGKE Master Mix(blue),the detection limit of adulterates in Aucklandia lappa Decne.and Inula helenium L.mixture sample was 5%.The 23 samples collected from the market were identified,results comparison was the same among ARMS detection,DNA barcoding,and plant classification.Conclusion The ARMS method established in this study can accurately identify Aucklandia lappa Decne.and Inula helenium L.,which has the characteristics of strong specificity and high sensitivity and simple operation,can provide basic research for solving the problem of admixture identification and technical support for the quality control of Aucklandia lappa Decne.medicinal materials.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective To explore the efficacy of 4R technology combined with prone five-direction cer-vical muscle strength training for neck type cervical spondylosis.Methods A total of 112 patients with neck and shoulder pain who visited the Affiliated Shapingba Hospital of Chongqing University and the Shapingba District Traditional Chinese Medicine Hospital in Chongqing from January to November 2024 were selected as research subjects.They were randomly assigned using a random number table method into an observation group and a control group,with 56 patients in each group.The observation group received 4R technology com-bined with prone five-direction cervical muscle strength training,while the control group received conventional rehabilitation treatment.Both interventions lasted for 4 weeks.Differences in Visual Analogue Scale(VAS)scores,Neck Disability Index(NDI)scores,and cervical range of motion in flexion,extension,lateral bending,and rota-tion were assessed before treatment and at 1 and 6 months after treatment for both groups.Results At 1 and 6 months of treatment,VAS scores in both groups decreased compared to before treatment,with the observation group lower than the control group,and the difference was statistically significant(P<0.05).At 1 and 6 months of treatment,NDI scores in both groups decreased compared to before treatment,with the observation group lower than the control group,and the difference was statistically significant(P<0.05).At 1 and 6 months of treatment,cervical flexion,cervical extension,and cervical lateral flexion in both groups increased compared to before treatment,and cervical rotation in the observation group increased compared to before treatment.Cervical extension and cervical rotation in the observation group were greater than those in the con-trol group,and only at 6 months of treatment was cervical lateral flexion in the observation group greater than in the control group,with all differences statistically significant(P<0.05).Conclusion The 4R technology combined with prone five-direction cervical muscle strength training can effectively improve cervical-type cer-vical spondylosis.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective To study the pathogenic bacteria infection in hospitalized diabetic foot patients in the Third People's Hospital of Yunnan Province and its correlation with different Wagner grades,to understand the the characteristics of pathogenic bacteria and related risk factors in hospitalized diabetic foot patients in the Third People's Hospital of Yunnan Province,and to further provide theoretical guidance for anti-infection treatment of these patients.Methods A retrospective analysis was conducted on the demographic data,severity of foot ulcers,and related laboratory test results of 536 patients with diabetic foot who were detected to have bacterial infection in the Third People's Hospital of Yunnan Province from January 2019 to January 2023.Results Among the 536 diabetic foot patients,pathogenic bacteria were cultured from 268 cases(50.0%)of Gram-positive bacterial infections,214 cases(39.9%)of gram-negative bacterial infections,2 cases(0.4%)of fungal infections,and 52 cases(9.7%)of mixed bacterial infections.The main pathogens among gram-positive bacteria were Staphylococcus aureus,Staphylococcus epidermidis and Enterococcus faecalis.for Gram-negative bacteria,the main pathogens were Escherichia coli,Enterobacter cloacae and Klebsiella pneumoniae.There were 31 cases of multi-drug resistant bacteria,and the multi-drug resistance rate was(5.78%).Among Gram-positive bacteria,all multidrug-resistant strains were Staphylococcus aureus,while among Gram-negative bacteria,the multi-drug resistant strains included Acinetobacter baumannii(1 case),Klebsiella pneumoniae(2 cases),Proteus common(2 cases),Pseudomonas aeruginosa(5 cases),Proteus mirabilis(1 case)and Enterobacter cloacae(1 case).The 536 patients were divided into Wagner grade 1 and 2 groups(78 cases),Wagner grade 3 group(274 cases),and Wagner grade 4 and 5 groups(184 cases).There were 73 cases of single bacterial infections and 5 cases of mixed bacterial infections in Wagner grade 1 and 2 group,including 51 cases(65.4%)of gram-positive bacteria,21 cases(26.9%)of gram-negative bacteria and 1 case(1.3%)of fungi.There were 248 cases of single bacterial infections and 26 cases of mixed bacterial infections in Wagner3 group,with 144 cases(52.6%)of gram-positive bacteria,103 cases(37.6%)of gram-negative bacteria,and 1 case(0.4%)with fungi.In the Wagner grade 4 and 5 groups,there were 163 cases of single bacterial infections and 21 cases of mixed bacterial infection,with 73 strains(39.7%)of gram-positive bacteria,90 strains(48.9%)of gram-negative bacteria and 0 strain(0%)of fungi.The predominant infectious pathogens in Wagner grades 1,2 and 3 were gram-positive bacteria,while those in Wagner grades 4 and 5 patients were mainly gram-negative bacteria.There were statistically significant differences in white blood cell counts,neutrophil percentage,bacterial classification,length of hospital stay,erythrocyte sedimentation rate and albumin levels among diabetic foot patients with different Wagner grades(P<0.01).With the increase of Wagner grade,patients had higher white blood cell counts and hypersensitive C-reactive protein levels,longer hospital stays,and lower albumin levels;however,there were no statistically significant differences in age,sex,duration of diabetes,smoking history,alcohol consumption history and history of hypertension(P>0.05).Conclusion The bacterial infection situation in patients with diabetic foot ulcers is related to different Wagner grades.The higher the Wagner grades,the greater the likelihood of infection with gram-negative bacteria.Antibiotics can be reasonably selected according to the Wagner grades of patients upon admission,actively controlling infection,while also enhancing,shortening hospital stays,and reducing amputation rates,thereby improving the prognosis of diabetic foot patients.

Objective To analyze the bacterial distribution characteristics,drug resistance characteristics and related risk factors of multidrug-resistant organisms(MDRO)in patients with diabetic foot infection(DFI)in some areas of Yunnan Province to provide empirical reference for clinical treatment.Methods Clinical data of 300 DFI patients admitted to the Department of Endocrinology of the Third People's Hospital of Yunnan Province from January 2019 to December 2023 were collected.Based on the results of drug sensitivity tests and matching of basic data,patients were divided into the MDRO group(n=60)and the non-MDRO group(n=240).A retrospective analysis was conducted on the distribution of pathogenic bacteria,drug resistance characteristics of MDRO and risk factors for MDRO infection in DFI patients.Results In 60 patients with MDRO infections,62 strains of MDRO were cultured,with 58 strains from single MDRO infections and 4 strains from mixed MDRO infections.Of the 60 patients,2 were cultured for 2 types of MDRO.Among the strains,there were 45 gram-positive bacteria(72.58％)which were all Staphylococcus aureus,17 strains of gram-negative bacteria(27.42％)mainly including Pseudomonas aeruginosa,Enterobacter cloacae and Klebsiella pneumoniae.Among common MDRO,Staphylococcus aureus showed complete resistance to penicillin G and oxacillin(100％),with high resistance to erythromycin and clindamycin(＞80％),but no resistance to tigacycline vancomycin was observed.The resistance of Klebsiella pneumoniae and Enterobacter cloacae to cephalosporin antibiotics was obvious,and the resistance rate to imipenem and amikacin was low.Pseudomonas aeruginosa was 100％resistant to ticacillin/clavulanate potassium,imipenem,tigacycline and cotrimoxazole,but showed no resistance to cefepime,ciprofloxacin,gentamicin and amikacin.There were statistically significant differences between the two groups in regional distribution,duration of diabetic foot,lower extremity arterial disease,venous plasma glucose levels and glycosylated hemoglobin(P＜0.05).Binary Logistic regression analysis showed that region and duration of diabetic foot disease were independent risk factors for MDRO infection in DFI patients(P＜0.05).Conclusion In some areas of Yunnan Province,the distribution of MDRO in DFI patients is mainly gram-positive bacteria,with varying antibiotic sensitivities among different pathogens.Multiple factors lead to MDRO infections in DFI patients,which assists clinical practitioners in early identification of high-risk DFI patients with MDRO infections and provide empirical reference for clinical treatment.

OBJECTIVE: To investigate the relationship between angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) and semen parameters. Methods： The semen samples of 820 male patients who were treated in the Reproductive Medicine Center of Taiyuan Central Hospital from August 2022 to August 2023 were retrospectively analyzed. The levels of AT1-AA and Ang Ⅱ of semen were detected by ELISA, and the function of AT1-AA was detected by cardiomyocyte beating assay in suckling rats. The patients were divided into low group, median group and high group according to the OD values of AT1-AA. The differences in general data and semen parameters between different groups were analyzed. And the correlation between AT1-AA level and semen parameters in semen of all study subjects was analyzed by the method of Spearman analysis. And the relationships between AT1-AA OD value, Ang Ⅱ level and semen parameters in the AT1-AA high value group were analyzed as well. RESULTS: AT1-AA was present in semen with good function. There was no significant difference in the general data of patients in different AT1-AA levels (P>0.05). In the comparison of semen parameters among the groups with different levels of AT1-AA, there were differences in sperm concentration, PR concentration, NP％, and ALH among the three groups (P<0.05). And AT1-AA OD value was positively correlated with total sperm count, sperm concentration, PR concentration, and NP％, and negatively correlated with semen volume (P<0.05). In the AT1-AA high value group, the OD value of AT1-AA in semen was negatively correlated with inactive sperm, and positively correlated with total motility (［PR+NP］％), curve rate, mean path rate, and ALH. However, there was no correlation between the level of Ang Ⅱ in semen and semen parameters (P>0.05). CONCLUSION The presence of AT1-AA in semen may be associated with the promotion of sperm motility.
Male ; Humans ; Autoantibodies ; Sperm Motility ; Semen ; Retrospective Studies ; Receptor, Angiotensin, Type 1/immunology* ; Animals ; Rats ; Angiotensin II ; Adult ; Sperm Count ; Semen Analysis ; Receptor, Angiotensin, Type 2/immunology*

OBJECTIVE: To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. METHODS: Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. CONCLUSIONS Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans ; Acupuncture Therapy ; Neoplasms/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People