AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Aim To investigate the effect of thioredox-in-interacting protein(TXNIP)on non-alcoholic fatty liver disease(NAFLD).Methods Littermate male wild(WT)mice and TXNIP gene whole-body knock-out(KO)mice were randomly divided into two groups:(1)normal diet(ND)group,and(2)The high-fat group,which was fed a high-fat diet(HFD)containing 60％fat for 12 weeks.Serum lipid-related indexes,liver injury indicators and hepatic fat content were detected using commercial kits.The protein lev-els of TXNIP,SLC25A1,SLC13A5,ACLY,CPT1a and PPARα were detected by Western blot.The gene ex-pressions of SLC25A1,SLC13A5 and ACLY were de-tected by RT-PCR.Results High fat diet increased TXNIP protein expression in the liver tissue.Compared with WT-HFD mice,the biochemical indexes in the se-rum and the liver of KO-HFD mice were improved.There was no significant difference in mRNA and pro-tein levels of SLC25A1 between the four groups of mice.For SLC13A5 and ACLY,the mRNA and protein levels of WT-HFD mice were up-regulated compared with WT mice,and these alterations were significantly restored in KO-HFD mice.Besides,compared with WT mice,the protein expressions of the fatty acid oxidation-related protein PPARα and CPT1a proteins in WT-HFD mice decreased,while the protein expressions of PPARα and CPT1 a in KO-HFD mice were significantly enhanced.Conclusion TXNIP gene knockout can improve hepatic steatosis and delay the progression of NAFLD by inhibiting the carbon flux of fatty acid syn-thesis and promoting fatty acid oxidation.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of gender on prognosis after transcatheter patent foramen ovale(PFO)closure in patients with cerebral infarction or transient ischemic attack.Methods A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack(TIA)who underwent PFO closure at our hospital between January 2013 and December 2023.The patients were grouped by gender,and related data were collected,including age,comorbidities,Risk of Paradoxical Embolism(RoPE)score,laboratory results,findings of transthoracic/transesophageal echocardiography(TTE/TEE),and post-procedural complications,such as device-related thrombosis(DRT),recurrent stroke,bleeding,and atrial fibrillation(AF).Results A total of 112 patients were enrolled,including 59 males and 53 females,at a mean age of 42.47±12.35 years.The females had significantly higher preoperative RoPE score than the males(6.6±1.4 vs 6.0±1.5,P=0.046),and a statistical difference was observed in the distribution of infarction sites between them(Chi-square=10.25,P=0.006),indicating that the males were prone to posterior circulation infarction.Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females(9.3±2.4 mm vs 7.6±2.0 mm,P<0.001).During a median follow-up of 4 years,the male group had 1 case of myocardial infarction,1 cerebral hemorrhage,1 paroxysmal AF,2 gingival bleeding episodes,and 1 skin ecchymosis.In the female group,1 case experienced pulmonary embolism,1 paroxysmal atrial fibrillation,3 gingival bleeding episodes,2 skin ecchymoses,2 recurrent cerebral infarctions,and 2 recurrent TIAs.There was no statistical difference in overall adverse events between gender(P=0.291).Although the females had higher rates of recurrent cerebral infarction and TIA,this difference lacked statistical significance(P=0.222).Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors,such as RoPE score,age,hypertension,coronary heart disease,and other factors,gender was not an independent predictor of composite endpoint events after surgery.Conclusion Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA.However,females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

OBJECTIVES: To explore the status and risk factors of neuropsychological development in small for gestational age (SGA) infants at corrected 12-24 months of age. METHODS: Clinical data were retrospectively collected for 754 SGA infants at corrected ages 12-24 months in Shenzhen Bao'an Women and Children's Hospital between April 2018 and December 2023. Developmental quotient (DQ) levels were analyzed. According to the presence of global developmental delay (GDD), participants were divided into a GDD group (71 cases) and a control group (683 cases), and the incidence and influencing factors of GDD were investigated. RESULTS: In the high-risk preterm SGA group, the total DQ and DQ in all domains were lower than in the full-term SGA group (P<0.017). The overall incidence of GDD was 9.4% (71/754) and increased with decreasing gestational age (P<0.017). Compared with the control group, the GDD group had higher proportions of males; low-risk and high-risk preterm birth; mothers with less than a bachelor's degree; multiple birth; neonatal hypoglycemia; neonatal pneumonia; neonatal respiratory distress syndrome; bronchopulmonary dysplasia; and, at corrected 12-24 months, low body weight, growth retardation, and microcephaly. The length of neonatal hospital stay was longer in the GDD group than in the control group (P<0.05). The weight-for-age Z score, length-for-age Z score, and head circumference-for-age Z score at birth and at corrected 12-24 months were lower in the GDD group than in the control group (P<0.05). Multivariable logistic regression showed that male sex and maternal education below a bachelor's degree were independent risk factors for GDD in SGA infants (P<0.05). CONCLUSIONS Neuropsychological development in preterm SGA infants is comparatively delayed; male SGA infants born to mothers with less than a bachelor's degree should receive priority attention.
Humans ; Female ; Male ; Infant, Small for Gestational Age/psychology* ; Risk Factors ; Infant ; Retrospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Infant, Newborn ; Child, Preschool

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Aim To investigate the effect of thioredox-in-interacting protein(TXNIP)on non-alcoholic fatty liver disease(NAFLD).Methods Littermate male wild(WT)mice and TXNIP gene whole-body knock-out(KO)mice were randomly divided into two groups:(1)normal diet(ND)group,and(2)The high-fat group,which was fed a high-fat diet(HFD)containing 60％fat for 12 weeks.Serum lipid-related indexes,liver injury indicators and hepatic fat content were detected using commercial kits.The protein lev-els of TXNIP,SLC25A1,SLC13A5,ACLY,CPT1a and PPARα were detected by Western blot.The gene ex-pressions of SLC25A1,SLC13A5 and ACLY were de-tected by RT-PCR.Results High fat diet increased TXNIP protein expression in the liver tissue.Compared with WT-HFD mice,the biochemical indexes in the se-rum and the liver of KO-HFD mice were improved.There was no significant difference in mRNA and pro-tein levels of SLC25A1 between the four groups of mice.For SLC13A5 and ACLY,the mRNA and protein levels of WT-HFD mice were up-regulated compared with WT mice,and these alterations were significantly restored in KO-HFD mice.Besides,compared with WT mice,the protein expressions of the fatty acid oxidation-related protein PPARα and CPT1a proteins in WT-HFD mice decreased,while the protein expressions of PPARα and CPT1 a in KO-HFD mice were significantly enhanced.Conclusion TXNIP gene knockout can improve hepatic steatosis and delay the progression of NAFLD by inhibiting the carbon flux of fatty acid syn-thesis and promoting fatty acid oxidation.

Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen(HBsAg)sero-clearance in patients with severe hepatitis B.Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020.Of them,7 patients(aged 36.57±3.15 years)achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares(with abrupt rise of ALT level to＞5 times the upper limit of normal during HBV infection)and were assigned into HBsAg clearance group,while the other 7 patients(aged 34.14±2.97 years)only obtained HBsAg decreased less than 1 g within 1 year after the onset(HBsAg non-clearance group).Then,multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients.Results The serum levels IFN-γ,IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group(P＜0.05),but no statistical differences were observed in other 39 cytokines between the 2 groups.And there were 5 cytokines having no mutual expression in both groups.The copy number of HBV DNA was positively correlated with serum HGF(r=0.675,P=0.008)and SDF-1α levels(r=0.587,P=0.027),while negatively with IP-10(r=-0.600,P=0.023)and MIG level(r=-0.640,P=0.014).Meanwhile,a positive correlation was found between HBsAg titer and IL12-p70 level(r=0.593,P=0.025),and a negative correlation between HBsAg titer and TNF-α level(r=-0.609,P=0.021).In addition,the serum total bilirubin level was positively correlated with the expression of SCGF-β(r=0.543,P=0.045).Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found,which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares.Meanwhile,it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

OBJECTIVE: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown. METHODS: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR. RESULTS: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment. CONCLUSION JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.
Exosomes/drug effects* ; Animals ; Carcinoma, Hepatocellular/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Liver Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Mice ; Humans ; Cell Line, Tumor ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Male ; Mice, Nude