OBJECTIVETo study the flavonoids of the aerial parts of Andrographis paniculata.

METHODTwelve flavonoids from the 85% EtOH extract were isolated by the silica gel column, Sephadex LH-20 column, ODS column chromatography and HPLC, and their structures were identified by the spectal analyses and chemical evidences.

RESULTThe 12 compounds were obtained and identified as 7-O-methylwogonin (1), 7-O-methyldihydrowogonin (2), 5-hydroxy-7, 8, 2', 5'-tetramethoxy-flavone (3), skullcapflavone-2'-methoxylether (4), 5-hydroxy-7, 8, 2', 3'-tetramethoxyflavone (5), 5, 4'-dihydroxy-7, 8, 2', 3'-tetramethoxyflavone (6), dihydroskullcapflavone (7), 5, 7, 8-trimethoxydihydroflavone (8), 5, 2'-dihydroxy-7, 8-dimethoxyflvone (9), andrographidine C (10), 5, 7, 4'-trihydroxyflavone (11), 5, 7, 3', 4'-tetrahydroxyflavone (12).

CONCLUSIONCompound 6 is a new naturally occurring product isolated from A. paniculata, and compound 8, 11 and 12 are obtained for the first time from the Andrographis species.

Andrographis ; chemistry ; Flavonoids ; chemistry ; isolation & purification ; Luteolin ; chemistry ; isolation & purification ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo study the diterpenoids in the 85% ethanol extract of the aerial parts of Andrographis paniculata.

METHODFourteen diterpenoids from the 85% EtOH extract were isolated by the silica gel, Sephadex LH-20, ODS column chromatography and HPLC, and their structures were identified by the spectal analyses and chemical evidences.

RESULTThe 14 compounds were obtained and identified as neoandrographolide (1), 3, 14-di-deoxyandrographolide (2), andrographolide (3), 14-deoxy-11, 12-didehydroandrographolide (4), 19-hydroxy-8 (17), 13-labdadien-15, 16-olide (5), 14-deoxy-andrographolide (6), 3-oxo-14-deoxy-andrographolide (7), isoandrographolide, (8), bisandrographolide (9, 10, 11), deoxyandrographiside (12), 14-deoxy-11, 12-didehydroandrographiside (13), andrographiside (14), respectively.

CONCLUSIONCompound 7 was a new natural product, and compound 5 was obtained for the first time from the Andrographis species.

Andrographis ; chemistry ; Diterpenes ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Tetrahydronaphthalenes ; chemistry ; isolation & purification

Objective To evaluate the effects of artery-interventional therapy and drug treatment on patients with symptomatic carotid artery total occlusion,and observe the follow-up results of cerebrovascular events after clinical interference.Methods According to patient′s intention,62patients with symptomatic carotid artery total occlusion,admitted to our hospitals from February 2004 to January 2009,were divided into artery-interventional therapy group(n=21)and drug treatment group (n=41).In the artery-interventional therapy group,patients were given revascularization of internal carotid by endovascular intervention.In the drug treatment group,patients were given aspirin,clopidogrel and statins.The major end-point outcome of follow-up survey was the 2-year functional prognosis evaluated by modified Rankin Scale(mRS),and Rank sum test was employed to compare the differences of mean rank of the 2 groups; the minor end-point outcome was the cardiovascular events,and Kaplan-Meier method and multivariate Cox regression were employed to analyze the median time and independent risk factors.Results During the 3,6 and 9 months,1 and 2 years of follow-up,mRS average ranks in the artery-interventional therapy group were statistically lower than those in the drug treatment group(P＜0.05).The median times of recurrence of cardio-cerebrovascular events in the artery-interventional therapy group and drug treatment group were(17.42±1.20)months(95％CI:15.07-19.76)and(19.43±1.51)months(95％CI:16.48-22.38),respectively,and Kaplan-Meier analysis showed no significant difference(P＞0.05).Survival Cox regression analysis showed that independent factors of cardio-cerebrovascular events were smoking(RR=3.189,95％CI:1.020-9.968,P=0.046),diabetes(RR=2.717,95％CI:1.113-6.631,P=0.028),and baseline NIHSS scores(RR=2.984,95％CI:1.049-8.485,P=0.040),but treatment methods(artery-interventional therapy and drug treatment)were not independent factors(RR=1.191,95％CI:0.430-3.296,P=0.737).Conclusion Artery-interventional therapy is superior to drug therapy in achieving better functional prognosis; however,the 2-year-follow-up shows that the artery-interventional therapy can not reduce the occurrence of cardio-eerebrovascular events.Smoking,diabetes and baseline NIHSS scores are independent factors of recurrence of cardio-cerebrovascular events.

UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risksUGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The ICvalues of icotinib and erlotinib against UGT1A1-mediated NCHN--glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with thevalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risksUGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risksUGT1A1 inhibition.

Urethral plate (UP)-preserving urethroplasty is simple and has few complications, but it may affect the development of penis in the long term and lead to recurrent chordee. In this study, we used obliquely cut UP to repair hypospadias with mild chordee after degloving (15°-30°) and compared the results with onlay urethroplasty to explore its rationality and feasibility. Between April 2018 and October 2020, 108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty. Clinical data were prospectively collected, and medium-term outcomes were assessed at follow-up. The complications were compared between the two groups. Forty-four patients underwent the modified onlay procedure (Group I), with follow-up time (mean ± standard deviation [s.d.]) of 23.2 ± 4.5 (range: 17-31) months. Sixty-four patients underwent a standard onlay procedure (Group II), with follow-up time (mean ± s.d.) of 39.7 ± 3.9 (range: 32-46) months. There was no difference in age at surgery. The urethral defect length and operative time were longer in Group I. Six cases of fistula and one case each of stricture and diverticulum were reported in Group I. In Group II, 11 cases of fistula and one case each of stricture and diverticulum were reported. The complication rates were 18.2% and 20.3% in Group I and Group II, respectively (P > 0.05). These medium-term follow-up results demonstrate that the modified onlay procedure (oblique cut UP urethroplasty) is a safe and feasible technique for hypospadias with mild chordee after degloving. Compared with standard onlay urethroplasty, this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications.
Male ; Humans ; Infant ; Hypospadias/surgery* ; Cicatrix/surgery* ; Constriction, Pathologic/surgery* ; Urethra/surgery* ; Diverticulum ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.
Child, Preschool ; Exchange Transfusion, Whole Blood/adverse effects* ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant ; Infant, Newborn ; Kernicterus/therapy* ; Phototherapy/methods* ; Retrospective Studies

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3'UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.
Animals ; Apoptosis ; genetics ; Apoptosis Regulatory Proteins ; deficiency ; genetics ; Base Sequence ; Bcl-2-Like Protein 11 ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Down-Regulation ; genetics ; Gene Silencing ; Male ; Membrane Proteins ; deficiency ; genetics ; Mice ; MicroRNAs ; genetics ; Proto-Oncogene Proteins ; deficiency ; genetics ; Rats ; Stomach Neoplasms ; genetics ; pathology