Objective To investigate the clinical features，laboratory findings，and prognosis of patients with autoimmune encephalitis positive for leucine rich glioma inactivated 1（LGI1）antibody. Methods We reviewed the clinical data of 11 patients with anti-LGI1 encephalitis hospitalized in Fu Yang People's Hospital from October 2019 to December 2024. Results All the 11 patients（100%）had cognitive function involvement，9（81.8%）had epileptic seizures，5（45.5%）had mental and behavioral abnormalities，4（36.4%）had sleep disorders，3（27.3%）had autonomic nervous dysfunction，2（18.2%）had faciobrachial dystonic seizures（FBDS），2（18.2%）had facial numbness，and 1（9.1%）had phantosmia and pruritus in both eyes and the neck. LGI1 antibody was positive in the serum of all the cases（100%）and present in the cerebrospinal fluid of 8 cases（72.3%）. Seven cases（63.6%）had hyponatremia，and 5 cases（45.5%）also had hypophosphatemia，hypocalcemia，and hypomagnesemia in addition to blood sodium lower than 134 mmol/L. Intracranial abnormalities were detected in 7 cases（63.6%）on magnetic resonance imaging. Electroencephalogram abnormalities were recorded in 6 cases（54.5%）. After immunosuppressive treatment，2 cases（18.2%）had recurrent symptoms，and 2 cases（18.2%）had residual mild memory impairment. In terms of prognosis，the modified Rankin Scale scores were generally favorable. Conclusion Anti-LGI1 encephalitis manifests as convulsions，FBDS，memory decline，mental and behavioral abnormalities，autonomic nervous dysfunction，sleep disorders，hyponatremia，and multiple electrolyte disorders such as hypomagnesemia，hypocalcemia，and hypophosphatemia when blood sodium is below 134 mmol/L. The prognosis with immunosuppressive treatment is favorable，but recurrent symptoms may occur.

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective To explore whether ferulic acid can inhibit the progression of T-cell acute lymphoblastic leukemia in vivo and in vitro by regulating PTEN/PI3K/AKT signaling pathway.Methods The T-cell acute lymphoblastic leukemia Jurkat cells were divided into the control group,the ferulic acid treatment group and the LY294002 treatment group for in vitro experiment.The cells in the control group were given normal culture;cells in the ferulic acid treatment group were given different concentrations(1.25,2.5,5,10,20,40,80,160 μmol/L)of ferulic acid,respectively,and the cell proliferation was detected by CCK-8 method,to screen the experimental concentration;cells in the LY294002 treatment group were given 50 μmol/L PI3K/AKT inhibitor LY294002.The cells proliferation,apoptosis and invasion were detected by clone formation assay,flow cytometry and Transwell assay.The relative expression levels of nuclear protein Ki67,proliferating cell nuclear antigen(PCNA),cleaved caspase-3,cleaved caspase-9,E-cadherin,N-cadherin,Vimentin,PTEN,p-PI3K,PI3K,p-AKT and AKT proteins were detected by Western blot.The nude mice models of transplanted tumors were constructed by 30 male BALB/c nude mice,and they were averagely divided into the normal group and the ferulic acid treatment group for in vivo experiment.The normal group was given normal saline by gavage,while the ferulic acid treatment group was given 75 mg/kg ferulic acid by gavage after inoculating Jurkat cells.The weight and volume changes of transplanted tumors were compared,and the levels of Ki67,cleaved caspase-3/caspase-3,E-cadherin,N-cadherin,PTEN,p-PI3K,PI3K,p-AKT and AKT in tumor tissues were detected.Results In vitro experiment,compared with the control group,the clone formation rate of cells,number of invasion cells,Ki67,PCNA,N-cadherin,Vimentin,p-PI3K/PI3K and p-AKT/AKT in the 5,10,20 μmol/L ferulic acid treatment group and the LY294002 treatment group were significantly decreased(P<0.05),while the apoptosis rate,cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,E-cadherin and PTEN were significantly increased(P<0.05).In vivo experiment,compared with the normal group,the weight and volume of tumors were reduced in the ferulic acid treatment group,Ki67,N-cadherin,p-PI3K/PI3K and p-AKT/AKT in tumor tissues were significantly decreased,cleaved caspase-3/caspase-3,E-cadherin and PTEN were significantly increased,with statistically significant differences(P<0.05).Conclusion Ferulic acid can inhibit the proliferation and invasion of T-cell acute lymphoblastic leukemia Jurkat cells in vivo and in vitro,and induce apoptosis,its mechanism may be related to the regulation of PTEN/PI3K/AKT signaling pathway.

Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.

Objective:To explore the association between cardiovascular health behaviors and hyperuricemia (HUA) among community residents of different age groups.Methods:It was a cross-sectional study. A total of 2 138 community residents aged (47.1±11.6) years with 1 012 males (47.3%) were selected by cluster sampling method as study subjects in Taiyuan Nanzhai Community from March to November 2020. There were 104 cases aged 8-18 years (underage group), 868 cases aged 19-44 years (youth group), 625 cases aged 45-59 years (middle-aged group), 375 cases aged 60-74 years (young elderly group), and 166 cases aged≥75 years (elderly group). Blood uric acid was measured and>420 μmol/L was defined as HUA, there were 385 cases with high uric acid level (HUA group) and 1 753 cases with normal uric acid levels (control group). The general information was collected by questionnaires, and general ergonomic indicators were measured on-site by medical personnel. The cardiovascular health behaviors included smoking, exercise, diet, and sleep in study subjects were documented. Multivariate logistic regression model was used to analyze the related factors of HUA.Results:Among 2 138 participants, 1 161 (54.3%) had never smoked (up to standard), and the order of proportion of non-smokers from high to low was underage group, elderly group, young elderly group, young group and middle-aged group ( P<0.001); 486(22.7%) people met the dietary standards, and the order of proportion of meeting the dietary standards from high to low was underage group, elderly group, young elderly group, middle-aged group, and young group ( P<0.001); 554(25.9%) people achieved physical fitness standards, and the order of the proportion of achieving physical fitness standards from high to low was young elderly group, middle-aged group, elderly group, underage group, and young group ( P<0.001); 783 (36.6%) people met the sleep standards, and the order of proportion meeting the sleep standards from high to low was underage group, youth group, middle-aged group, young elderly group, and elderly group ( P<0.001). Among the participants, only 39 (1.8%) met the standards for all 4 types of behaviors; 485 (22.7%), 1 229 (57.5%), and 424 (19.8%) had low, medium, and high total scores for ideal cardiovascular health behaviors, respectively. The total score of ideal cardiovascular health behaviors ranked from high to low was elderly group, young elderly group, underage group, middle-aged group, and young group ( P<0.001). The multivariate logistic regression analysis showed that body mass index (BMI) ( OR=1.125, 95% CI: 1.086-1.165) was positively correlated with HUA, while female ( OR=0.241, 95% CI: 0.182-0.320), total score of cardiovascular health behaviors (compared to lower level, intermediate level: OR=0.186, 95% CI: 0.127-0.273, high level: OR=0.038, 95% CI: 0.020-0.072), and number of achieved healthy behavior items ( OR=0.757, 95% CI: 0.621-0.922) were negatively correlated with HUA. Conclusions:The underage group has the highest number of people who meet the smoking, dietary, and sleep standards, the young and elderly group has the highest number of people who meet the exercise standards, and the elderly group has the highest total score for ideal cardiovascular health behaviors. There is a positive correlation between BMI and HUA, while there is a negative correlation of HUA with female, the total score and number of achieved items of cardiovascular health behaviors.

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
Humans ; Pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Gasdermins ; Chemoradiotherapy/adverse effects* ; Rectal Neoplasms/surgery* ; Caspases/metabolism* ; Diarrhea/chemically induced* ; Leukopenia/genetics* ; Genetic Variation ; Dermatitis

Objective:To investigate the efficacy of dapagliflozin combined with tirofiban in patients with type 2 diabetes mellitus complicated with coronary heart disease.Methods:A total of 120 patients with type 2 diabetes mellitus and coronary heart disease treated in Fuyang People′s Hospital from January to August 2022 were prospectively selected as subjects. According to different treatment methods, they were divided into control group and experimental group. The control group was treated with tirofiban, and the experimental group was treated with dapagliflozin combined with tirofiban. The efficacy and safety of treatments between the two groups were compared.Results:After 3 months of treatment, fasting plasma glucose (FPG), 2 h postprandional blood glucose (2 h PG), glycated hemoglobin (HbA 1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), D-dimer (D-D) and fibrinogen (FIB) levels in 2 groups were decreased compared with before treatment:experimental group: (7.33 ± 1.77) mmol/L vs. (9.45 ± 2.05) mmol/L, (10.33 ± 2.07) mmol/L vs. (13.57 ± 2.88) mmol/L, (7.22 ± 1.28) % vs. (9.25 ± 1.78) %, (1.98 ± 0.29) mmol/L vs. (6.05 ± 1.24) mmol/L, (2.95 ± 0.37) mmol/L vs. (4.35 ± 0.76) mmol/L, (0.78 ± 0.23) mg/L vs. (1.85 ± 0.79) mg/L, (2.57 ± 0.37) g/L vs. (7.15 ± 1.36) g/L, control group: (8.21 ± 1.85) mmol/L vs. (9.68 ± 2.17) mmol/L, (11.78 ± 2.26) mmol/L vs. (13.89 ± 3.02) mmol/L, (8.25 ± 1.36) % vs. (9.37 ± 1.86) %, (2.77 ± 0.42) mmol/L vs. (6.08 ± 1.22) mmol/L, (3.84 ± 0.44) mmol/L vs. (4.27 ± 0.72) mmol/L, (1.34 ± 0.52) mg/L vs. (1.81 ± 0.72) mg/L, (5.25 ± 0.84 ) g/L vs. (7.11 ± 1.28) g/L, the differences were statistically significant ( P< 0.05). The levels of FPG, 2 h PG, HbA 1c, TC, LDL-C, D-D and FIB between the two groups were statistically significant ( P<0.05). High density lipoprotein cholesterol (HDL-C) level, left ventricular ejection fraction (LVEF), cardiac blood transfusion volume (CO), stroke output (SV), thrombin time (TT) and partially activated prothrombin time (APTT) were all increased: experimental group: (1.76 ± 0.30) mmol/L vs. (1.07 ± 0.28) mmol/L, (68.64 ± 12.91) % vs. (45.05 ± 12.24) %, (4.88 ± 0.91) L/min vs. (3.95 ± 1.12) L/min, (53.66 ± 5.43) ml/min vs. (43.27 ± 4.88) ml/min, (31.83 ± 4.39) s vs. (23.25 ± 3.44) s, (13.85 ± 2.17) s vs. (10.75 ± 1.56) s, control group: (1.43 ± 0.26) mmol/L vs. (1.06 ± 0.24) mmol/L, (60.37 ± 11.86) % vs. (45.42 ± 12.41) %, (4.37 ± 0.84) L/min vs. (4.17 ± 1.16) L/min, (47.86 ± 5.27) ml/min vs. (43.36 ± 4.94) ml/min, (27.24 ± 3.91) s vs. (23.78 ± 3.62) s, (12.74 ± 1.94) s vs. (10.89 ± 1.78) s, the differences were statistically significant ( P<0.05). There were significant differences in HDL-C, LVEF, CO, SV, TT and APTT between the two groups ( P<0.05). The incidence of adverse reactions in experimental group was lower than that in control group during treatment: 5.00% (3/60) vs. 16.67% (10/60), and the difference was statistically significant ( P<0.05). Conclusions:Dapagliflozin combined with tirofiban in the treatment of patients with type 2 diabetes mellitus complicated with coronary heart disease has obvious curative effect, and can improve blood glucose and blood lipid levels, coagulation function and cardiac function, with high safety.

Objective:colorectal cancer is one of the common malignant tumors in the gas-trointestinal tract.Oxaliplatin is the first-line drug for the treatment of advanced colorectal cancer,but drug resistance often occurs.The mechanism of CXCR4 in oxaliplatin resistance of colon cancer is not clear.This study intends to explore the mechanism of CXCR4 mediated oxaliplatin resistance and the potential therapeutic value of CXCR4 inhibitor AMD3100.Methods:oxaliplatin resistant strains HCT116 were constructed.The expression of CXCR4 and the phosphorylation level of PI3K-Akt signal pathway were detected by Q-PCR and Western blot.The phosphorylation level of PI3K-Akt signal pathway was detected by Q-PCR and Western blot.The effect of AMD3100 an-tagonizing CXCR4 or combined application of Akt inhibitor LY294002 on oxaliplatin resistance of drug-resistant cells was detected by CCK8.Results:CCK-8 was used to detect the proliferation activity of Oxaliplatin in HCT116 drug resistant group compared with control cells in the absence of drugs and at different concentrations.The results showed that there was no significant change in the activity of the resistant strains,while the control cells showed a significant decrease.Q-PCR and Western blot showed that the expression of CXCR4 and the phosphorylation level of PI3K-Akt increased significantly in the drug-resistant group(P＜0.05).After administration of CXCR4 inhibitor AMD3100,CXCR4 expression and PI3K-Akt phosphorylation decreased significantly(P＜0.05).AMD3100 enhanced the sensitivity of drug-resistant cell lines to oxaliplatin.The combination of AMD3100 and Akt inhibitor LY294002 can further enhance the sensitivity of drug-resistant cell lines to oxaliplatin.Conclusion:CXCR4 mediated activation of PI3K-Akt signaling pathway plays an important role in the resistance of colon cancer to oxaliplatin.AMD3100 may become a potential therapeutic drug against chemoresistance of colon cancer.