OBJECTIVETo compare therapeutic effects of acupuncture and Western medicine for promoting ovalation on endocrine dysfunctional infertility.

METHODSTwo hundred and forty cases of infertility were randomly divided into an acupuncture group (n = 160) and a Western medicine group (n = 80). They were treated with acupuncture and clomiphene respectively and their therapeutic effects were compared.

RESULTSThe pregnancy rate was 65.0% in the acupuncture group and 45.0% in the Western medicine group with a significant difference between the two groups (P < 0.05).

CONCLUSIONAcupuncture can cure endocrine dysfunctional infertility.

Acupuncture Points ; Acupuncture Therapy ; Clomiphene ; Humans ; Infertility ; Medicine, Chinese Traditional ; Pregnancy Rate

Objective·To discover lead compounds with 6,11-dihydro-5H-benzo[a]carbazole as core scaffold that can inhibit the proliferation of cervical cancer cells. Methods?·?A series of 6,11-dihydro-5H-benzo[a]carbazole derivatives and analogs were synthesized using Fischer indole synthesis method, and their anticancer activity against HeLa cells was tested in vitro by CCK8 test. Results?·?2-Methoxy-6,11-dihydro-5H-benzo[a]carbazole and 8-chloro-2-methoxy-6,11-dihydro-5H-benzo[a]carbazole could significantly inhibit the proliferation of HeLa cells with the half maximal inhibitory concentration ( IC50) values of 9.61?μmol/L and 16.52?μmol/L, respectively. Conclusion?·?Two objective lead compounds were found. Among 6,11-dihydro-5H-benzo[a]carbazole derivatives, compounds with methoxy group at the C-2 position of the core scaffold show better activity against proliferation of cervical cancer cells.

BACKGROUNDInvasive aspergillosis (IA), which is mainly caused by Aspergillus fumigatus (A. fumigatus), is a major cause of morbidity and mortality in immunocompromised patients. Despite considerable progress in currently available antifungals the mortality still remains high in critically ill patients. U0126 which is a highly selective inhibitor of MEK1 and MEK2 in the RAF/MEK/ERK pathway in mammalian cells has been demonstrated to have an anti-proliferative role in cancer cells. The purpose of this study was to explore the role of U0126 on growth inhibition and activation of mitogen-activated protein kinases (MAPKs) in A. fumigatus.

METHODSGermination percentage and hyphae growth in A. fumigatus treated with U0126 were observed and compared with untreated controls. Western blotting analysis was used to detect changes in activation of SakA, MpkA and MpkB.

RESULTSU0126 inhibited germination and hyphae growth in A. fumigatus and enhanced the phosphorylation of SakA and MpkA under oxidative stress. U0126 at 10 µmol/L did not block the activation of MpkB during nitrogen starvation stress.

CONCLUSIONU0126 shows promise as an antifungal candidate and the MAPK pathway may be a possible antifungal drug target for A. fumigatus.

Aspergillus fumigatus ; drug effects ; enzymology ; growth & development ; Butadienes ; pharmacology ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Mitogen-Activated Protein Kinases ; metabolism ; Nitriles ; pharmacology

To evaluate the hepatotoxicity risks of physcion on the basis of the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1(UGT1A1 enzyme). The monomers were added into the rat liver microsomes to test the hepatotoxicity by using bilirubin as UGT1A1 enzyme substrate, with apparent inhibition constant K_i as the evaluation index. Liver microsome incubation in vitro was adopted to initiate phase Ⅱ metabolic reaction and investigate the inhibitory effect of physcion. Then the phase Ⅰ and Ⅱ metabolic reactions were initiated to investigate the comprehensive inhibition of metabolites and prototype components. The results showed that when only the phase Ⅱ reaction was initiated, physcion directly acted on the UGT1A1 enzyme in a prototype form, exhibited weak inhibition and the inhibition type was mixed inhibition; When the phase Ⅰ and Ⅱ reactions were initiated simultaneously, the inhibitory effects of physcion on UGT1A1 enzyme became strong and the inhibition type was mixed inhibition, suggesting that physcion had phase Ⅰ and Ⅱ metabolic processes, and the metabolites had strong inhibitory effect on UGT1A1 enzyme. This experiment preliminarily proved that the metabolites of physcion may be the main components to induce hepatotoxicity.
Animals ; Chemical and Drug Induced Liver Injury ; Emodin ; analogs & derivatives ; toxicity ; Glucuronosyltransferase ; metabolism ; Kinetics ; Microsomes, Liver ; drug effects ; Rats

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.
Apigenin/chemistry* ; Bilirubin/chemistry* ; Drug Interactions ; Glucuronosyltransferase/metabolism* ; Humans ; Hydrogen Bonding ; Microsomes, Liver/drug effects* ; Molecular Docking Simulation

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.
Anthraquinones/toxicity* ; Chemical and Drug Induced Liver Injury ; Drugs, Chinese Herbal/toxicity* ; Glucuronosyltransferase/metabolism* ; Humans ; Liver/enzymology* ; Microsomes, Liver/drug effects* ; Rhizome

Objective: To explore the clinical effects of pulsed dye laser (PDL) dynamically combined with triamcinolone acetonide (TAC) in the treatment of keloids. Methods: A retrospectively observational study was conducted. From April 2015 to October 2020, 34 keloid patients (46 keloids) who met the inclusion criteria were admitted to Huaihe Hospital of Henan University. The patients were divided into TAC group and dynamic treatment group according to their treatment methods. There were 18 patients (26 keloids) in TAC group, including 8 males and 10 females, aged (30±12) years, who were treated with TAC injection alone. There were 16 patients (20 keloids) in dynamic treatment group, including 6 males and 10 females, aged (26±11) years, who were treated with TAC injection, PDL, or PDL combined with TAC injection according to the Vancouver scar scale (VSS) score before each treatment. Before the first treatment (hereinafter referred to as before treatment) and 12 months after the first treatment (hereinafter referred to as after treatment), the keloids were assessed by VSS, patient and observer scar assessment scale (POSAS), and the effect of keloids on the quality of life of patients was evaluated with dermatology life quality index (DLQI) scale. Twelve months after treatment, the curative effect of keloid was evaluated according to the VSS score and the effective rate was calculated. The first effective time and the cumulative times of TAC injection at the first effective time, the number of follow-up and the occurrence of adverse reactions of keloids within 12 months after treatment were recorded, and the incidence of adverse reactions was calculated. Data were statistically analyzed with paired sample t test, independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: The total VSS scores of patients' keloids in TAC group and dynamic treatment group 12 months after treatment were significantly lower than those before treatment (with t values of 7.53 and 8.09, respectively, P<0.01), and the total scores of pigmentation and vascularity in VSS and POSAS, the total POSAS score, and the DLQI scale score were significantly lower than those before treatment (with Z values of -3.71, -4.04, -4.21, -4.11, -3.76, -3.73, -3.92, and -3.93, respectively, P<0.01). The total scores of pigmentation and vascularity in VSS and POSAS of patients' keloids in dynamic treatment group 12 months after treatment were significantly lower than those in TAC group (with Z values of -2.03 and -2.12, respectively, P<0.05). Twelve months after treatment, the effective rate of patients' keloids in dynamic treatment group was significantly higher than that in TAC group (χ²=3.88, P<0.05). The first effective time of patients' keloids in dynamic treatment group was 5.5 (2.0, 6.0) months, which was significantly shorter than 6.0 (2.3, 10.3) months in TAC group (χ²=4.02, P<0.05). The cumulative times of TAC injection at the first effective time of patients' keloids in dynamic treatment group was 3.2±1.7, which was significantly less than 4.2±1.8 in TAC group (t=2.09, P<0.05). The number of follow-up of patients' keloids within 12 months after treatment in dynamic treatment group was significantly more than that in TAC group (t=-2.94, P<0.01), and the total incidence of adverse reactions was lower than that in TAC group but without statistically significant difference (P>0.05). Conclusions: Compared with TAC injection alone, PDL dynamically combined with TAC in the treatment of keloid can shorten the effective time, reduce the number of TAC injection, and improve the patient's compliance and clinical efficacy.
Female ; Humans ; Keloid/pathology* ; Lasers, Dye/therapeutic use* ; Male ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; Triamcinolone Acetonide/therapeutic use*

OBJECTIVE: To investigate the expression and clinical significance of soluble interleukin-2 receptor(sIL-2R) in patients with multiple myeloma(MM). METHODS: 54 newly diagnosed MM patients in the Second Affiliated Hospital of Fujian Medical University from February 2020 to December 2021 were selected as the observation group, and 60 healthy people in our hospital in the same period were selected as the control group. The expression levels of sIL-2R in the serum of the two groups were detected by enzyme-linked immunosorbent assay. The differences of sIL-2R expression level among different clinical parameter groups in MM patients were compared. The clinical parameters include:gender, age, ISS stage, hemoglobin, albumin, serum creatinine, lactate dehydrogenase and β₂-microglobulin, blood calcium, bone marrow plasma cell ratio and treatment response. The relationship between sIL-2R expression level and progression-free survival(PFS) and overall survival(OS) in MM patients were analyzed. RESULTS: The expression of serum SIL-2R in MM patients was significantly higher than that in healthy control group (P<0.05). The expression of sIL-2R in MM patients who did not achieve complete remission(CR) was significantly higher than those of CR patients (P=0.037). There was no significant difference in the expression of serum sIL-2R between the groups of different sex, age, ISS stage, hemoglobin concentration, albumin content, serum creatinine level, lactate dehydrogenase level, the content of β₂-microglobulin, the concentration of blood calcium, and the proportion of bone marrow plasma cells(P>0.05). The PFS of sIL-2R high expression group(15 months) was shorter than that of sIL-2R low expression group (22 months), which was significant difference (P=0.041). But there was no significant difference in OS between sIL-2R high expression group and sIL-2R low expression group (P=0.124). Univariate analysis results showed that the high expression of serum sIL-2R was associated with poor PFS in MM patients. Multivariate analysis results showed that the high expression of serum sIL-2R was still an independent adverse prognostic factor for PFS in MM patients, However, the expression of serum sIL-2R was not statistically significant in evaluating OS in MM patients by univariate and multivariate analysis. CONCLUSION The expression of serum sIL-2R in MM patients was significantly higher than that in healthy people. Serum sIL-2R is an independent prognostic factor of PFS in MM patients.
Humans ; Calcium ; Clinical Relevance ; Creatinine ; Lactate Dehydrogenases ; Multiple Myeloma ; Receptors, Interleukin-2

Objective: Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the L-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO

Dendrobium denneanum have been used for a long time as rare medicinal herbs in traditional Chinese medicine. Our previous works found that ether extract of D. denneanum had higher anticancer activities than alcohol or water extract,thus with better development prospects. Quantitative proteomics based on SILAC technique was used to investigate the anticancer mechanism of D. denneanum on lung tumor cell line A549,and 4 855 proteins were detected in A549 cells. Quantitative proteomics experiments found that 193 proteins of A549 cells were up-regulated,and 44 proteins were down-regulated by ether extract of D. denneanum. Those proteins are associated with synthesis,transport and metabolism of biological macromolecules,chaperone,DNA repair,oxidoreductase,cell adhesion,cell cycle,apoptosis and autophagy. Through the function analysis of differentially expressed proteins,it was inferred that ether extract of D. denneanum caused cell protein metabolism disorder,endoplasmic reticulum stress response,abnormal self-repair mechanism of cells,damage of cell adhesion and proliferation; besides,it caused a dramatic increase in ROS level in A549 cells,and upset the balance of intracellular oxidation reduction system. Affected by the above factors,lung cancer cells initiated apoptosis and autophagy,which accelerated cell death. This research explains the anticancer mechanism of D. denneanum from the perspective of quantitative proteomics,and lays a foundation for future research and development of new anticancer drugs based on ether extract of D. denneanum.
A549 Cells ; Animals ; Apoptosis ; Dendrobium ; Ether ; Humans ; Lung Neoplasms ; Proteomics