OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts

Objective:To explore the influencing factors of olfactory impairment in patients with obstructive sleep apnea（OSA） and establish a nomogram prediction model. Methods:A total of 100 OSA patients were enrolled. Snap&Sniff olfactory test was used to evaluate the olfactory identification function and olfactory threshold of the patients. According to the scoring criteria, either olfactory identification scores below 14 points or olfactory threshold scores below 3 points was defined as olfactory impairment. Multivariate logistic regression analysis was used to explore the influencing factors of olfactory impairment in OSA. The nomogram model was constructed by using the R 4.4.2 software package. ROC curve, calibration curve and decision curve were used to evaluate the predictive efficacy, consistency and clinical utility of the model. Results:A total of 55 of 100 OSA patients had olfactory impairment. The results of multivariate logistic regression analysis showed that age, ESS score, MoCA score, and apnea-hypopnea index（AHI） were the influencing factors of olfactory impairment in OSA. Based on the above parameters, a nomogram model was established. The ROC curve analysis showed that the AUC was 0.897（95%CI 0.834-0.961）, indicating that the model had good predictive ability. The calibration curve showed that the predicted probability of the model fits the actual probability well. Decision curve analysis showed that when the threshold probability was in the range of 0-0.9, the model had a high clinical net benefit rate. Conclusion:Age, ESS score, MoCA score and AHI are the influencing factors of olfactory impairment in patients with OSA. The nomogram model constructed based on the above factors has good predictive value, which is conducive to the clinical multi-angle understanding of OSA and the formulation of scientific prevention and treatment measures.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Nomograms ; Olfaction Disorders/etiology* ; Logistic Models ; Middle Aged ; Male ; Female ; ROC Curve ; Adult ; Aged

Objective:To investigate how gut microbiota changes during prostate cancer radiotherapy and decipher the relationship of gut microbiota with disease progression and chronic radiation enteritis.Methods:Thirty-one patients with prostate cancer were included in this study,admitted to The First Affiliated Hospital of Xinjiang Medical University from September 2022 to December 2023.The clinical data and stool samples of the patients were collected,and patients were followed up.The collected stool specimens were subjected to 16S rRNA se-quencing to detect gut microbiota and bioinformatics analysis.Results:The relative abundance of phyla such as Firmicutes and Actinobac-teria increased,and that of Bacteroidetes decreased(P<0.05)with an increasing radiotherapeutic dose,while beta diversity was significantly higher(P=0.001).The relative abundance of the phylum Actinobacteria was significantly higher in the prostate cancer progression group than in the non-progression group(P<0.05),the relative abundances of genera such as Sutterella and Haemophilus were significantly higher in the progression group(P<0.05).That of Verrucomicrobia and its offshoots in Akkermansia was higher in the chronic radiation enteritis than in the non-enteritis group(P<0.05),while the relative abundances of Coprococcus_1 and Catabacter in the non-enteritis group were higher than those in the enteritis group(P<0.05).Conclusions:Radiotherapy dose accumulation significantly remodeled the floral structure.Sutterella and Haemophilus of the phylum Proteobacteria might be key flora in prostate cancer recurring early after treatment.An augmen-ted abundance of Akkermansia might increase the risk of chronic radiation enteritis,whereas the flora under the Lachnospiraceae branch might exert aprotective effect against chronic radiation enteritis.

Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

Objective:To investigate how gut microbiota changes during prostate cancer radiotherapy and decipher the relationship of gut microbiota with disease progression and chronic radiation enteritis.Methods:Thirty-one patients with prostate cancer were included in this study,admitted to The First Affiliated Hospital of Xinjiang Medical University from September 2022 to December 2023.The clinical data and stool samples of the patients were collected,and patients were followed up.The collected stool specimens were subjected to 16S rRNA se-quencing to detect gut microbiota and bioinformatics analysis.Results:The relative abundance of phyla such as Firmicutes and Actinobac-teria increased,and that of Bacteroidetes decreased(P<0.05)with an increasing radiotherapeutic dose,while beta diversity was significantly higher(P=0.001).The relative abundance of the phylum Actinobacteria was significantly higher in the prostate cancer progression group than in the non-progression group(P<0.05),the relative abundances of genera such as Sutterella and Haemophilus were significantly higher in the progression group(P<0.05).That of Verrucomicrobia and its offshoots in Akkermansia was higher in the chronic radiation enteritis than in the non-enteritis group(P<0.05),while the relative abundances of Coprococcus_1 and Catabacter in the non-enteritis group were higher than those in the enteritis group(P<0.05).Conclusions:Radiotherapy dose accumulation significantly remodeled the floral structure.Sutterella and Haemophilus of the phylum Proteobacteria might be key flora in prostate cancer recurring early after treatment.An augmen-ted abundance of Akkermansia might increase the risk of chronic radiation enteritis,whereas the flora under the Lachnospiraceae branch might exert aprotective effect against chronic radiation enteritis.

Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

In the process of seeking new strategies to improve the efficacy of antidepressants,traditional Chinese medicine inter-vention has gradually revealed its unique prevention and treat-ment advantages.The dopamine reward system is closely in-volved in the pathological occurrence and development of depres-sion.Currently,research has mostly focused on the functional mechanism of a specific nucleus in the dopamine reward system,and there is less research focused on the functional mechanism of the neural circuit.In the current micro research on reward cir-cuits,the association between abnormal reward circuits and neg-ative emotions such as anxiety and depression has been widely recognized.Traditional Chinese medicine intervention can exert antidepressant effects by influencing reward circuits.This article provides a review on the loop mechanism of dopamine reward system involvement in depression and research on traditional Chinese medicine intervention.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Objective To investigate the effect of the aqueous extract of Chuan Xiong Rhizoma(CR)on brain metastasis of melanoma B16F10 cells in mice.Methods C57BL/6J mouse models of brain metastasis of melanoma were established by ultrasound-guided intraventricular injection of Luc-labeled B16F10 cells,and brain tumor growth was monitored by in vivo imaging.The mouse models were then randomized for daily gavage of saline or aqueous extract of CR(equivalent crude drug concentration of 1 mg/g).Behavioral tests were used to evaluate the neuroprotective effects of CR in the tumor-bearing mice,and the changes in proteins associated with blood-brain barrier integrity,neuronal cell proliferation and apoptosis,and microglial cell apoptosis and activation were observed using immunofluorescence assay.The efficacy of CR combined with temozolomide(25 mg/kg)against brain metastases of B16F10 cells was observed by in vivo imaging.Results CR-treated mouse models did not show obvious progression of brain metastases and had a reduced rate of body weight loss and lowered protein expressions of ZO-1,claudin-5,occludin,P-gp,TNF-α,AQP4 and PDGFRβ.In the behavioral tests,the CR-treated mice showed prolonged stay on the wooden stick with a shortened time of sticky stick removal.Immunofluorescence assay showed increased proliferation and decreased apoptosis of neuronal cells and microglia in CR-treated mice.CR treatment significantly increased the levels of CD86,CD206,IL-4 and IL-10 and decreased the levels of CD163 and IL-1β in the microenvironment of brain metastases.The mice receiving combined treatments with CR and temozolomide showed significantly lower intensity of fluorescent signals in the brain than those treated with temozolomide alone.Conclusion CR does not promote brain metastasis of melanoma while inducing opening of the blood-brain barrier,and its combined use with TMZ results in enhanced inhibition against brain metastasis of melanoma B16F10 cells in mice.