Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

OBJECTIVE: Our study aimed to conduct genomic characterization of Salmonella strains carrying the bla _NDM-1 gene in the intestinal tract of healthy individuals. The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations, and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes. METHODS: We performed antimicrobial susceptibility testing and employed second- and third-generation sequencing techniques to analyze Salmonella strains harboring the bla _NDM-1 gene, to surveil drug-resistant bacteria in the intestines of healthy subjects. Sequence comparison was conducted using both core- and pan-genome approaches. Concurrently, conjugation experiments were carried out to assess the efficiency of plasmid transfer. RESULTS: We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China. This strain harbored an IncHI2/IncHI2A plasmid carrying bla _NDM-1 along with multiple antibiotic resistance genes (ARGs). Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs. Pan-genomic analysis revealed that bla _NDM-1-positive plasmids could traverse bacterial species barriers, facilitating cross-host transmission. CONCLUSION This study marks the first detection of bla _NDM-1 in Salmonella strains isolated from healthy individuals. We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying bla _NDM-1, which have the potential to be harbored and transmitted among healthy individuals. Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.
beta-Lactamases/genetics* ; Plasmids/genetics* ; Humans ; Anti-Bacterial Agents/pharmacology* ; China ; Microbial Sensitivity Tests ; Salmonella typhimurium/isolation & purification* ; Salmonella/isolation & purification* ; Salmonella Infections/microbiology*

Objective Our study aimed to conduct genomic characterization of Salmonella strains carrying the b/aNDM-1 gene in the intestinal tract of healthy individuals.The objectives were to underscore the importance of genomic surveillance for drug resistance in both commensal and pathogenic bacteria among healthy populations,and to establish protocols for regulating drug resistance plasmids based on the completion of a comprehensive map of drug resistance plasmid genomes.Methods We performed antimicrobial susceptibility testing and employed second-and third-generation sequencing techniques to analyze Salmonella strains harboring the b/aNDM-1 gene,to surveil drug-resistant bacteria in the intestines of healthy subjects.Sequence comparison was conducted using both core-and pan-genome approaches.Concurrently,conjugation experiments were carried out to assess the efficiency of plasmid transfer.Results We isolated a carbapenem-resistant Salmonella enterica serovar Typhimurium strain from a healthy food worker in China.This strain harbored an lncHI2/lncHI2A plasmid carrying blaNDM-1 along with multiple antibiotic resistance genes(ARGs).Our findings highlight the potential for asymptomatic carriers to facilitate the transmission of ARGs.Pan-genomic analysis revealed that b/aNDM-1-positive plasmids could traverse bacterial species barriers,facilitating cross-host transmission.Conclusion This study marks the first detection of b/aNDM-1 in Salmonella strains isolated from healthy individuals.We underscore the risk associated with the transmission of conjugative hybrid plasmids carrying blaNDM-1,which have the potential to be harbored and transmitted among healthy individuals.Enhanced surveillance of drug-resistant pathogens and plasmids in the intestinal microbiota of healthy individuals could provide insights into the risk of ARG transmission and pathways for population-wide dissemination via ARG transfer factors.

With high accuracy and precision,next generation sequencing (NGS) has provided a powerful tool for clinical testing of genetic diseases.To follow a standardized experimental procedure is the prerequisite to obtain stable,reliable,and effective NGS data for the assistance of diagnosis and/or screening of genetic diseases.At a conference of genetic testing industry held in Shanghai,May 2019,physicians engaged in the diagnosis and treatment of genetic diseases,experts engaged in clinical laboratory testing of genetic diseases and experts from third-party genetic testing companies have fully discussed the standardization of NGS procedures for the testing of genetic diseases.Experts from different backgrounds have provided opinions for the operation and implementation of NGS testing procedures including sample collection,reception,preservation,library construction,sequencing and data quality control.Based on the discussion,a consensus on the standardization of the testing procedures in NGS laboratories is developed with the aim to standardize NGS testing and accelerate implementation of NGS in clinical settings across China.

Objective To evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy(RNU) for upper tract urothelial carcinoma (UTUC).Methods The data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied.There were 69 males and 79 females,aged from 34 to 82 years old (average 68 years old).83 patients were accompanied with hydronephrosis.80 patients were renal pelvic carcinoma.32 patients had the history of smoking.24 patients had the history of ureteroscope.68 patients had the tumor larger than 3 cm.Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions.We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher' s exact test.Cancer specific survival was analyzed using the Kaplan-Meier method,with the log-rank test used to assess significance.A Cox proportional hazard model was used for multivariate analysis.Results Of the 148 patients,non-muscle invasive (Tis、Ta and T1) tumors of primary UTUC and bladder recurrence were 51 (34.5％) and 119 (80.4％),respectively.High grade (G3) tumors of primary UTUC and bladder recurrence were 41 (27.7％) and 53(35.8％),respectively.During follow-up,94 (63.5％) experienced bladder recurrence once and 54 (36.5％) experienced multiple bladder recurrence.The median follow-up time was 59.5 (rang 8-142) months,48 (32.4％) patients died of UTUC.The grade of bladder cancer recurrence correlated with the grade (P =0.046),muscle-invasion (P =0.002) and tumor architecture (P =0.034) of the primary UTUC;muscle-invasive bladder cancer recurrence associated with that of the primary UTUC (P =0.009);bladder multiple recurrence related to gender (P =0.007).On multivariate logistic regression analysis,the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive (HR =5.512,95％ CI 1.654-18.37,P =0.004) and high grade (HR =3.948,95％ CI 1.589-9.813,P =0.004) bladder recurrence tumor.The muscle invasion of primary UTUC (HR =3.498,95％ CI 1.569-7.803,P =0.002) was a prognostic factor for cancer specific survival on multivariate Cox regression analysis.Conclusions Muscle-invasive UTUC tend to predict high risk bladder recurrence tumor,and the female could be more likely to appear multiple recurrence tumor.The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival.

[Objective] To investigate the clinical value of using prospective ECG-gating Helical protocol in whole aorta and coronary arteries CT angiography combined with low tube voltage,low contrast medium injection rate and dose technology.[Methods]A total of 60 patients (heart rate≤ 75 bpm and normal heart rhythm) with suspected aortic disease or post-operation were randomly divided into 2 groups:G1 (n =30;tube voltage:80 kV;contrast medium injection rate:3 mL/s;contrast medium dose:0.65 mL/kg)and G2 (n =30;tube voltage:120 kV;contrast medium injection rate:4 mL/s;contrast medium dose:1.2 mL/kg).The two groups underwent aorta angiography with prospective ECG-gating Helical protocol by using 320-detector CT.The mean CT values and standard deviation of aorta,coronaries and adjacent adipose tissue were measured,signal to noise ratio (signal-to-noise ratio,SNR)and contrast to noise ratio (contrast-to-noise ratio,CNR) were calculated.The subjective quality scoring of 3-d post-processing images were evaluated independently by 2 senior radiologists.The mean CT values and standard deviation of aorta,coronaries and adipose tissue,SNR,CNR,subjective quality scoring,contrast medium dose and radiation dose were compared and analyzed.[Results] The abnormal and normal rate of aorta in two groups were 83.33％ (25/30),16.67％ (5/30) and 86.67％ (26/30),13.33％(4/30);while the abnormal and normal rate of coronary arteries in two groups were 43.33％ (13/30),56.67％ (17/30) and 53.33％(16/30),46.67％ (14/30).SNR values of ascending aorta,descending aorta,abdominal aorta,superior mesenteric artery,bilateral renal artery,left main coronary artery,left anterior descending branch,left circumflex branch,right coronary artery and CNR values of abdominal aorta,superior mesenteric artery,bilateral renal artery,left anterior descending branch,left circumflex branch had no statistical significance,while the other indicators were significant differences between the two groups.The radiation dose and the contrast medium dose of G1 was significantly lower than G2 (P ＜ 0.05).There was no difference in the subjective image quality of 3D post-processing images between the two groups (P ＞ 0.05).[Conclusions] Using prospective ECG-gating Helical protocol in whole aorta and coronary arteries CT angiography combined with low tube voltage,low contrast medium injection rate and low contrast medium dose technology can help to reduce radiation and contrast medium dose without impacting on the imaging quality satisfactorily.

[Objective] To measure the diameter of the superior rectal vein (SRV) & theinferior mesenteric vein (IMV) by CT and analyze their relationship with lymphatic metastasis of rectal carcinoma.And to discuss the feasibility of utilizing SRV to prcdict lymph node metastasis of rectal cancer.[Methods] The CT imaging and pathological data of 105 rectal carcinoma patients were analyzed retrospectively.We measured and compared the diameter of every patient's SRV & IMV by CT in the presence and absence of microvascular tumor thrombus,signet ring cell,lymph node metastasis and distant metastasis.The accuracy of predicting lymph node metastasis for rectal carcinoma by the diameter of SRV were evaluated by ROC curve.[Results] There were statistical differences in the diameters of SRV and IMV between rectal cancer group with lymph node metastasis (D =4.34 mm,D =5.00 mm) and without (D =3.56 mm,D =4.81 mm;P ＜ 0.001,P =0.023).The differences were significant in the diameter of SRV between rectal cancer group with microvascular tumor thrombus or signet ring cell and without (P =0.019,P =0.044).However,the diameter of IMV showed no statistical difference between rectal cancer group with microvascular tumor thrombus or signet ring cell and without (P =0.605,P =0.663).And there was no statistical difference in the diameter of SRV or IMV between rectal cancer patients with distant metastasis and without (P ＞ 0.05).Regarding 3.75 mm as the cut-off value for the diameter of SRV to predict lymph node metastasis for rectal cancer patients,the sensitivity was 90.9％ and the specificity was 82.0％.Regarding 4.65 mm as the cut-off value for the diameter of IMV to predict lymph node metastasis for rectal cancer patients,the sensitivity was 87.3％ and the specificity was 38％.[Conclusions] It is completely feasible to utilize the diameter of SRV measured by CT to predict lymph node metastasis of rectal carcinoma with high sensitivity,accuracy,and relatively high specificity.

Objective: To evaluate the impacts of the prognostic factors of T2N0M0 upper tract urothelial carcinoma (UTUC) for Chinese patients.Methods: A retrospective study was conducted including 235 patients who were diagnosed with T2N0M0 UTUC in our hospital and received radical nephroureterectomy (RNU) or partial ureterectomy during January 2000 and December 2013.The 3 and 5-year can-cer-specific survival rates and bladder recurrence-free survival rates of all the patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between the two were compared using the Log-rank test.Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model.Results: A total of 235 patients were included in this study, including 95 (40.4%) male patients and 140 (59.6%) female patients.The mean age was 66.73±10.49 years.The median follow-up time was 53 (rang: 3-142) months, and during the follow-up, 74 (31.5%) patients died of UTUC after a median of 35 months,and 96 (40.9%) patients developed intravesical recurrence after a median of 19.5 months.The 3 and 5-year cancer-specific survival rates of all the patients were 89.1% and 85.9%, respectively;the bladder recurrence-free survival rates were 85.5% and 80.2%, respectively.The independent prognostic factors of cancer-specific mortality were tumor age elder than 55 years (HR=3.138, 95%CI: 1.348-7.306, P=0.008) and diameter larger than 5 cm (HR=3.320, 95%CI: 1.882-5.857, P<0.001).The independent prognostic factors of bladder recurrence-free survival were ureter tumor (HR=1.757, 95%CI: 1.159-2.664, P=0.008) and lower tumor grade (HR=1.760, 95% CI: 1.151-2.692, P=0.009).Conclusion: T2N0M0 UTUC has a better cancer-specific survival.The intravesical recurrence was equivalent to non-muscle invasive UTUC but earlier.The tumor diameter larger than 5 cm and the patient age elder than 55 years were independently associated with cancer-specific mortality;the primary tumor located in ureter and lower tumor grade were more likely to develop intravesical recurrence.

Objective:To study the mechanism of anti-proliferative effect of lupeol on highly metastatic human hepatocellular car-cinoma HCCLM3 cells. Methods:CCK-8 assay was performed to evaluate the effects of lupeol at different concentration on cell viability in 12-48 h. Caspase inhibitors were used to identify the subtypes of caspases activated during lupeol-induced cell death. The effects of lupeol on the mRNA expression of caspase family and Bcl-2 related genes were detected by real-time PCR. The effects of lupeol on HC-CLM3 cell phase distribution were investigated by flow cytometry. Results:Compared with the control group, lupeol could inhibit HC-CLM3 cell proliferation in a concentration-dependent manner with IC50 of 93 μmol·L-1 in 24h. The number of HCCLM3 cells in the period of G2/M was increased by 1-fold when the lupeol concentration was within 60-100 μmol·L-1 . Lupeol could activate the path-way of caspase, and the mRNA expression of caspase-3 was elevated by 50%-150% when compared with that in the control group. Mo-reover, the mRNA expression of p53 and Bax were increased above 1-fold by lupeol at 100 μmol·L-1 , and the Bcl-2 and PARP ex-pression were significantly suppressed by lupeol at 60-100 μmol·L-1(P<0. 05 or P<0. 01). Conclusion:The results indicate that lupeol has anti-proliferative effect on the liver cancer cells, which is beneficial to the prevention and treatment of liver cancer.

Yolk sac tumor (YST) is a rare germ cell neoplasm of childhood that usually arises from the testis or ovary. The rare cases of YST in various extragonadal locations have been reported, but the primary intrarenal YST is even more uncommon. Here, we report a case of a primary intrarenal YST with tumor thrombus of the inferior vena cava and left renal vein in a 2-year-old boy, with an emphasis on the CT features. To our knowledge, this is the first reported case of an intrarenal YST with intravascular involvement.
Child, Preschool ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal/*diagnosis/pathology/ultrasonography ; Renal Veins/pathology/*radiography ; Thrombosis/pathology/radiography ; *Tomography, X-Ray Computed ; Vena Cava, Inferior/pathology/*radiography