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 assess the risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)bloodstream infection(BSI)and 28-day short-term mortality in elderly patients,and provide reference for the pre-vention and treatment of CRAB BSI.Methods Clinical data of patients aged ≥60 years and diagnosed with AB BSI in a hospital in Yulin City from January 2013 to December 2022 were retrospectively analyzed,including demogra-phic and microbiological characteristics,as well as clinical outcomes of the patients.Variables which were significant in univariate analysis were selected for multivariate analysis using binary logistic regression model and Cox propor-tional hazards model.Independent risk factors for infection were further determined,and survival analysis was per-formed using Kaplan-Meier curve.Results A total of 150 patients were included in the study,out of which 16 pa-tients(10.7％)had CRAB BSI and 134 had carbapenem-sensitive AB(CSAB)BSI.The 28-day short-term mortali-ty of AB BSI in elderly patients was 15.3％(23/150,95％CI:9.6％-21.1％),and the short-term mortality of CRAB BSI was higher than that of CSAB([56.3％,9/16]vs[10.4％,14/134]).Deep venous catheterization(OR:15.598,95％CI:1.831-132.910)and combined infections of other sites(OR:15.449,95％CI:1.497-159.489)were related to CRAB BSI in elderly patients.The independent risk factors for 28-day mortality in elderly patients with AB BSI were hemodialysis(OR:11.856,95％CI:2.924-48.076),intensive care unit admission(OR:9.387,95％CI:1.941-45.385),and pulmonary infection being suspected source of bacteremia(OR:7.019,95％CI:1.345-36.635).Conclusion The occurrence of CRAB BSI in elderly patients is related to the combined infection of other sites and deep vein catheterization.Hemodialysis,admission to ICU,and pulmonary infection being suspected source of bacteremia are independent risk factors for the prognosis of AB BSI in elderly patients.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Abstract: Objective　To understand the clinical manifestations, symptoms, treatment and recovery of neonates infected with Omicron variant (BA.5.1.3) of SARS-CoV-2, and provide a certain reference for subsequent diagnosis and treatment of related diseases. Methods　The clinical manifestations, epidemiology, auxiliary examinations, and treatment processes of the neonate aged 4-day-old who was community-acquired infection of variant BA.5.1.3 in Sanya was retrospectively analyzed. Results　The neonate's mother was identified as a close contact with patients with coronavirus disease 2019 (COVID-19) one hour before delivery, and tested positive for nucleic acid within 24 hours after delivery. But her breast milk, amniotic fluid, placenta, and umbilical cord were not detected for nucleic acid test after delivery. The nucleic acid test of the neonate was negative within 24 hours after birth. Then he was transferred to the hotel for isolation. Before the transfer, the mother and baby stayed in the same room and ate breast milk but the mother did not wear any mask. The neonate didn't have nucleic acid test on the second and third days of his life, and the nucleic acid test of the neonate was positive on the fourth day, negative on the fifth day, and positive on the sixth day. Then he was transferred to the designated hospital of COVID-19 for treatment. The neonate had no cough, no fever, yellow skin, abdominal distension, general breast feeding, and good reaction. On admission, the laboratory examination showed that blood routine examination and electrolyte were normal, and the myocardial enzyme and liver and kidney functions were normal. The bilirubin was significantly increased (449.3 μmol/L). The nucleic acid test of the neonate was positive and his chest imaging results were normal. The treatment measures were mainly isolation, feeding, blue light fading, close monitoring of vital signs, and antiviral drugs were administered. Jaundice subsided and abdominal distension was relieved after 6 d of treatment, and the treatment process was smooth without complications. Conclusions　The results suggest that the neonates are susceptible to Omicron variant BA.5.1.3 and prone to aggregation. The evidence of vertical transmission is insufficient and the clinical symptoms of neonates infected with Omicron variant BA.5.1.3 are mid, with no involvement of organ damage of the heart, liver, kidney, brain, and other organs.

Abstract: Objective　To explore the clinical characteristics of nucleic acid negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicron variant BA. 5.1.3) in Sanya area, and to provide evidence for understanding its clinical characteristics. Methods　A retrospective analysis was performed on 14 neonates with negative nucleic acid delivered by pregnant women who tested positive for SARS-CoV-2 (Omicron variant BA.5.1.3) in Sanya Central Hospital (the Third People's Hospital of Hainan Province) from June 2022 to September 2022 (observation group, n=14). The corresponding nucleic acid-negative newborns delivered by pregnant women detected negative with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) were set as the control group (n=56), and the general data and clinical characteristics of neonates in the two groups were compared. Results　There was no significant difference between the observation group and the control group in pregnancy diabetes, pregnancy induced hypertension, gestational pre-eclampsia, fetal intrauterine distress, premature rupture of membranes (P>0.05); there was no significant difference between the observation group and the control group in terms of sex, gestational age, birth weight, age, mode of delivery, birth Apgar score, heart screening, pulmonary disease, glucose 6-phosphate dehydrogenase (G6PD) deficiency, thalassemia, breast milk jaundice, hemolytic jaundice (P>0.05). The bilirubin level, blue light irradiation cases and the duration of blue light irradiation of the newborns in the observation group at 7 days after birth were higher than those in the control group (P<0.05); the ratio of blood oxygen saturation ≥ 90% in the observation group was lower than that in the control group (21.43% vs 89.29%, P<0.05), and the ratio of blood oxygen saturation occasionally<90% was higher than that in the control group (57.14% vs 10.71%, P<0.05). The ratio of blood oxygen saturation<90% had no significant difference compared with that in the control group (7.14% vs 0, P>0.05), and the ratio of blood oxygen saturation reduced to the required oxygen uptake was higher than that in the control group (14.29% vs 0, P<0.05). Conclusions　The jaundice manifestation of the nucleic acid-negative newborns delivered by pregnant women infected with SARS-CoV-2 (Omicronon variant strain BA.5.1.3) in Sanya area is relatively obvious, with blood oxygen saturation easily lower than 90% and even requiring oxygen inhalation in severe cases.

Abstract: Objective　To investigate the clinical characteristics and diagnosis key points of brain abscess caused by Nocardia asiatica, and provide a clinical basis for diagnosing and treating intracranial infection caused by Nocardia. Methods　A case of pulmonary Nocardia asiatica complicated with brain abscess diagnosed at the Second Affiliated Hospital of Hainan Medical University was selected to analyze the clinical manifestations, cerebrospinal fluid characteristics, pulmonary and cranial imaging features, and treatment plan, and to summarize the diagnosis and treatment experience. Results　The patient was an elderly woman with a history of diabetes, dry cough was the first symptom without fever or headache. At the beginning of the course, it was diagnosed as pulmonary infection and tuberculosis in the local hospital, and received conventional antimicrobial and anti-tuberculosis therapies, but showed no improvement. The patient developed progressive limb weakness, followed by consciousness disorders, and coma. Cerebrospinal fluid (CSF) adenosine deaminase and lactate dehydrogenase were not abnormal, CSF pressure, protein and white blood cells were high, mainly with multiple nuclear cells. CSF glucose and chloride were normal in the early stage of the disease, but decreased significantly in the later stage. Metagenomic analysis of cerebrospinal fluid indicated Nocardia asiatica with a specific sequence number of 537. Lung CT showed exudation, abscess, and cavity in the right lung. Skull MRI scan + enhancement suggested multiple scattered abscesses in both cerebral hemispheres. The abscesses were of different sizes and showed ring enhancement, with extensive surrounding edema, and ventricular compression. After treatment with meropenem, linezolid, and compound sulfamethoxazole tablets, the cerebrospinal fluid recovered, and the lesions in the lungs and intracranial structures improved. Conclusions　Brain abscess caused by Nocardia asiatica is similar to the tuberculous brain in clinical symptoms, cerebrospinal fluid examination, craniocerebral imaging, so we should be alert to the possibility of Nocardia infection in patients with diabetes. At the same time, metagenomic testing of the cerebrospinal fluid can help confirm the diagnosis. The mortality and disability rates of brain abscess caused by Nocardia are high. Early diagnosis and treatment can improve the prognosis.

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis