This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

Objective To evaluate the performance of an improved DeepSurv model for survival analysis in lung cancer patients,and investigate key factors affecting the prognosis of lung cancer.Methods The lung cancer data from the SEER database(2018-2021)was used in the study,and the DeepSurv model was optimized by incorporating a self-attention mechanism,a residual network,a LIME module and an entropy regularization term to enhance prediction accuracy and interpretability.Model performance was assessed using C-index and Brier score,and the improved model was utilized to evaluate the effects of various features on the prognosis of lung cancer.Results The improved DeepSurv model achieved a C-index of 0.852 and a Brier score of 0.139.Feature importance analysis identified age as the primary determinant of the survival of lung cancer patients.Conclusion The improved DeepSurv model outperforms both the Cox proportional hazards model and the original DeepSurv model in terms of accuracy,robustness and interpretability,offering a novel methodology for personalized medicine and survival analysis.

Objective To develop a prediction model for placenta previa in early pregnancy by analyzing embryo implantation sites and related clinical factors,in order to provide an objective basis for early risk identification.Methods A retrospective cohort study was conducted on 232 singleton pregnant women delivering in our hospital between September 2020 and March 2024.According to the final pre-delivery ultrasound findings,they were divided into placenta previa group(n=78)and a non-placenta previa group(n=154).Their ultrasound parameters[distance from lower gestational sac margin to cervical os,implantation site(lower/middle-upper uterine segment),and implantation position(anterior/posterior wall)],and clinical data[age,gravidity(categorized as<2 or≥2 pregnancies),parity(<2 or≥2 deliveries),and history of intrauterine procedures were collected through electronic medical records.Univariate analysis was used to screen potential predictors(P<0.1),and multivariate logistic regression analysis was employed to identify the predictors(P<0.05)for placenta previa.Then a nomogram prediction model was constructed,which was internally validated with Bootstrap(1 000 bootstrap resamples)and assessed for discrimination with area under the receiver operating characteristic curve(AUC)and for calibration with Hosmer-Lemeshow goodness-of-fit test.Results The placenta previa group showed significantly advanced age(≥35 years),lower education level(≤high school),multigravidity(≥2 pregnancies),multiparity(≥2 deliveries),more intrauterine procedures,distance of gestational sac-to-cervical os<5.5 mm,and larger proportion of lower uterine segment implantation than the non-placenta previa group(all P<0.1).But there were no statistical differences between the 2 groups in proportion of posterior wall implantation,history of cesarean section or assisted reproductive technology(ART).Multivariate logistic regression analysis confirmed lower uterine segment implantation(OR=40.40,95%CI:14.68～136.19,P<0.001),posterior wall implantation(OR=2.73,95%CI:1.27～6.28,P=0.013),and intrauterine procedures(OR=3.48,95%CI:1.65～7.70,P=0.001)as independent risk factors.The model based on these predictors demonstrated excellent discrimination(AUC value=0.84,95%CI:0.79～0.90)and calibration(Hosmer-Lemeshow test Chi-square=3.455,P=0.750).Conclusion Lower uterine segment/posterior wall implantation and intrauterine procedures are independent risk factors for placenta previa.Our nomogram model based on these factors shows good predictive efficiency,and can provide reference for early recognition of pregnant woman with high-risk placenta previa.

Water-soluble silver nanoclusters(DHLA-AgNCs)with red fluorescence emission were synthesized using silver nitrate(AgNO3)as silver source,dihydrolipoic acid(DHLA)as ligand and sodium borohydride(NaBH4)as reducing agent by one-pot method.Based on the selective quenching of DHLA-AgNCs by tetracycline(TC),a rapid and selective fluorescence analysis method for detection of TC was constructed by monitoring the fluorescence intensity change at 650 nm.Under the optimal detection conditions,the fluorescence quenching efficiency of DHLA-AgNCs showed good linear relationship with concentration of TC within the range of 10.0-120.0 μmol/L,and the limit of detection(LOD)was 0.39 μmol/L.This method was successfully applied to detection of TC in milk samples,with spiked recoveries ranging from 99.5%to 102.5%,and relative standard deviations(RSDs)less than 5%.This method had the advantages of simplicity,rapidity,strong specificity and low cost,and thus provided a simple and feasible strategy for selective detection of TC.

Objective To evaluate the performance of an improved DeepSurv model for survival analysis in lung cancer patients,and investigate key factors affecting the prognosis of lung cancer.Methods The lung cancer data from the SEER database(2018-2021)was used in the study,and the DeepSurv model was optimized by incorporating a self-attention mechanism,a residual network,a LIME module and an entropy regularization term to enhance prediction accuracy and interpretability.Model performance was assessed using C-index and Brier score,and the improved model was utilized to evaluate the effects of various features on the prognosis of lung cancer.Results The improved DeepSurv model achieved a C-index of 0.852 and a Brier score of 0.139.Feature importance analysis identified age as the primary determinant of the survival of lung cancer patients.Conclusion The improved DeepSurv model outperforms both the Cox proportional hazards model and the original DeepSurv model in terms of accuracy,robustness and interpretability,offering a novel methodology for personalized medicine and survival analysis.

Objective:To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma.Methods:A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results:① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group ( P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group ( P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower ( P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group ( P=0.002), whereas the incidence of grade 3 diarrhea was lower ( P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea ( P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group ( P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group ( P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group ( P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups ( P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively ( P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively ( P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively ( P=0.373) . Conclusion:In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.

Objective:To elucidate the complete genomic characteristics of the Akabane virus (AKV) DHL10M117 strain and the Tibet orbivirus (TIBOV) DH10M1019 strain, isolated from mosquito specimens collected in 2010 from Dehong prefecture, Yunnan province.Methods:The complete RNA virus sequences were obtained using metatranscriptomics and high-throughput sequencing.Results:The complete genome sequences of the DHL10M117 strain, consisting of the S, M, and L gene segments with lengths of 856 bp, 4 309 bp, and 6 869 bp, respectively, were acquired. Phylogenetic analysis indicated that the DHL10M117 strain is an AKV strain, closely related to the AKV strain DHL10M110, isolated from Yunnan. The S and M segment phylogenetic trees revealed that the strain is closely related to AKV strains circulating in southern China and Japan, and distantly related to strains from Australia, suggesting that this strain belongs to the Asian lineage with distinct regional characteristics. Homology analysis confirmed that the gene sequences of the S, M, and L segments of the DHL10M117 strain showed 100% nucleotide and amino acid identity with the DHL10M110 strain. Additionally, the complete genome sequences of the DH10M1019 strain, comprising ten gene segments (Seg-1 to Seg-10) with lengths of 3 950 bp, 2 904 bp, 2 769 bp, 1 978 bp, 1 772 bp, 1 638 bp, 1 165 bp, 1 142 bp, 1 103 bp, and 832 bp respectively, were obtained. Phylogenetic analysis showed that DH10M1019 is a TIBOV strain, with eight gene segments (Seg-1 to Seg-4, Seg-6, Seg-8 to Seg-10) clustering with known strains in the same major branch, while Seg-5 and Seg-7 formed distinct branches, independent of known reference strains, suggesting that DH10M1019 may represent a new serotype of TIBOV.Conclusions:Through complete genome sequence analysis, it was confirmed that DHL10M117 and DH10M1019 are AKV and TIBOV, which provided a scientific basis for the epidemiological characterisation, pathogenicity analysis and investigation of the two viruses.

Objective:The complete genome sequence characteristics of Quang Binh virus (QBV) and Manglie virus (MaV) isolated from mosquitoes in Daluo Town, Menghai county.Methods:Mosquitoes collected in Daluo Town, Menghai county in July 2012 were used for virus isolation. The nucleic acid was extracted from the supernatant of Aedes albopictus cell line (C6/36) showing cytopathic effect (CPE) positivity, and was sent to a company for sequencing after library construction. Phylogenetic and nucleotide/amino acid sequence similarity analysis was performed using DNAStar, Maff, and other softwares.Results:RNA libraries of strains BNDL1205 and BNDL1227 yielded 67 336 692 and 61 259 266 qualified gene sequences (reads) respectively. After assembly and alignment, sequences of lengths 10 865 bp and 10 864 bp were obtained. Sequence analysis indicated that they belong to QBV, with strains BNDL1205 and BNDL1227 clustering with QBV (strain VN180) isolated from Vietnam on the same evolutionary branch, sharing nucleotide similarity of 84.2% and 84.1%, and amino acid similarity of 94.6% and 94.4% respectively. RNA library of strain BNDL1223 yielded 48 622 610 qualified reads. After assembly and alignment, three gene fragments (Contigs) matched MaV. Further merging using SeqMan produced a complete nucleotide sequence of 9 219 bp. Analysis revealed that strain BNDL1223 is closely related to MaV isolated in Yunnan in 2018, sharing nucleotide similarity of 97.8% and amino acid similarity of 99.2%.Conclusions:During the investigation of arboviruses in mosquitoes in Daluo Town, Menghai county, three strains of viruses were identified: 2 strains of QBV and 1 strain of MaV. Local mosquitoes play a significant role in the transmission of QBV and MaV, necessitating enhanced monitoring and detection of local vector mosquitoes.