Objective To evaluate the efficacy of Puerariae lobatae radix （PLR） and Anemarrhenae Rhizoma （AR） in preventing and treating Alzheimer’s disease （AD） and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride （AlCl₃） and D-galactose （D-gal） for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased （P<0.05）, while the SOD content was decreased considerably （P<0.01）. The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences （P<0.05）. The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

OBJECTIVE: To investigate the early clinical efficacy of single-position O-arm navigation-assisted oblique lateral interbody fusion(OLIF) combined with minimally invasive percutaneous pedicle screw fixation(PPS) in the treatment of lumbar spondylolisthesis. METHODS: A retrospective analysis was conducted on 22 patients with lumbar spondylolisthesis who underwent OLIF-PPS surgery including 11 males and 11 females with a mean age of (64.6±1.5) years old ranging from 49 to 80 years old between April 2021 and June 2023. All patients presented with lumbosacral pain, lower limb radiating pain, numbness, and had poor responses to conservative treatment. Surgical time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Clinical outcomes were evaluated using the visual analogue scale(VAS) and Oswestry disability index(ODI) preoperatively at 3 days after operation and the final follow-up. Standing lumbar anteroposterior and lateral X-rays were performed to measure disc height(DH), slippage degree, vertebral reduction rate, pedicle screw accuracy, and cage subsidence. RESULTS: All surgeries were successfully completed with a mean follow-up of (27.1±2.2) months (range 18 to 36 months). The mean surgical time was (76.1±12.2) min (range 60 to 93 min), intraoperative blood loss was (86.3±32.2) ml (range 40 to 113 ml), and hospital stay was (7.1±1.2) days. Postoperative VAS significantly improved from (7.2±0.7) preoperatively to (2.3±0.5) at 3 days after operation and (1.7±0.2) at the final follow-up (P<0.05). ODI decreased from (68.5±7.2)% preoperatively to (30.3±3.1)% at 3 days after operation and (16.6±1.6)% at the final follow-up (P<0.05). DH increased from (8.5±1.7) mm preoperatively to (18.1±1.4) mm at 3 days after operation and (17.2±1.1) mm at the final follow-up (P<0.05). Slippage degree improved from (24.1±4.6)% preoperatively to (10.3±4.2)% at 3 days after operation and (10.1±3.2)% at the final follow-up (P<0.05). A total of 88 pedicle screws were implanted with an excellent rate of 98% (86/88). Complications included transient left hip flexion weakness (2 cases) and left anteromedial thigh pain (1 case), all resolved during follow-up. No incision hematoma, infection, screw loosening, or cage subsidence occurred. CONCLUSION Single-position O-arm navigation-assisted OLIF combined with PPS demonstrates satisfactory early clinical efficacy for lumbar spondylolisthesis, with advantages including minimal invasiveness, significant pain relief, effective vertebral reduction, and low complication rates.
Humans ; Male ; Female ; Spondylolisthesis/diagnostic imaging* ; Middle Aged ; Aged ; Spinal Fusion/methods* ; Lumbar Vertebrae/diagnostic imaging* ; Minimally Invasive Surgical Procedures/methods* ; Pedicle Screws ; Aged, 80 and over ; Retrospective Studies

OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL). METHODS: The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis. RESULTS: A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005). CONCLUSION The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Asparaginase/therapeutic use* ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Prognosis ; Retrospective Studies ; Survival Rate ; Polyethylene Glycols

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dysfunctions related to thinking, learning, and memory of the brain. AD has multiple pathological characteristics with complicated causes, constructing a suitable pathological model is crucial for the research of AD. Microfluidic chip technology integrates multiple functional units on a chip, which can realize microenvironmental control similar to the physiological environment. It is well applied in the construction of pathological model, early diagnosis as well as drug screening of AD. This paper focuses on the construction of AD microfluidic chips model from the perspective of cell type, culture formats and the chips structure as well as the research progress of microfluidic chips in AD application based on the pathological characteristics of AD, which will provide a reference for further elucidation of AD mechanism and drug development.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.