Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species / 药物分析学报

The canonical transient receptor potential channel(TRPC)proteins form Ca2+-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1-/-mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/-mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1-/-cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factor-kappa B(NF-κB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca2+influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Recent advances in small-molecule inhibitors targeting influenza virus glycoproteins / 药学学报

Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.

Total serum bilirubin and bilirubin to albumin values in predicting neonatal acute bilirubin encephalopathy: a multicenter study / 中国新生儿科杂志

Objective:To study the predictive value of total serum bilirubin (TSB) and the ratio of bilirubin to albumin (B/A) in neonatal acute bilirubin encephalopathy (ABE).Methods:Neonates with extremely severe hyperbilirubinemia (TSB≥425 μmol/L) treated in the Nanjing Maternal and Child Health Hospital, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Northwest Women and Children's Hospital, Yinchuan Maternal and Child Health Hospital and Liaocheng People's Hospital from March 2018 to August 2019 were selected as prospective subjects for this study. According to the score of brain injury induced by bilirubin, the subjects were divided into ABE group and non-ABE group, and the predictive value of TSB peak and B/A for neonatal ABE were analyzed.Results:A total of 194 infants with extremely severe hyperbilirubinemia were recruited in this study, including 20 in ABE group and 174 in non-ABE group. The peak value of bilirubin ranged from 427 to 979 μmol/L. The optimal critical values of TSB peak value and B/A for ABE prediction were 530 μmol/L and 9.48, respectively. The sensitivity and specificity of ABE prediction were 85.0% and 92.8% when combined with TSB peak and B/A values.Conclusions:TSB peak combined with B/A value can effectively identify neonatal ABE. When the TSB peak value was greater than 530 μmol/L and the B/A value was greater than 9.48, the neonates had a higher risk of neonatal ABE.

Treatment of Diabetic Nephropathy from Collateral Diseases： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is classified into "collateral diseases" in traditional Chinese medicine （TCM）. This study reviewed， analyzed， and discussed the clinical and basic research on DN treatment from collateral diseases in recent years. The main TCM therapeutic principles of DN from collateral diseases are dominated by reinforcing the deficiency and dredging collaterals. Fundamental research showed that the relevant mechanism is related to the improvement of oxidative stress and endoplasmic reticulum stress， reduction of inflammatory responses， coping with microcirculation disorder and vascular endothelial damage， and alleviation of renal injury. The theory of collateral diseases can provide ideas for clinical and basic research on DN and also shows advantages in clinical application. However， the present clinical application of this therapeutic principle is mainly based on the combination of deficiency-reinforcing drugs and blood stasis-resolving drugs. In spite of some overlap， blood stasis syndrome and collateral diseases are not in the same category. Therefore， the current diagnosis and treatment of DN from collateral diseases fail to combine with the changes of collateral vessels， main pathogenic factors， and the changes of the secondary pathogenesis. The application of classic collateral drugs such as pungent drugs， rattan drugs， and insect drugs has not been paid enough attention in syndrome differentiation and treatment. In addition， there is a lack of correlation with clinical symptoms and laboratory indexes in the basic research on the treatment of DN by Chinese medicinal prescriptions. Accordingly， the present study advocates systematic research on DN under the guidance of collateral diseases theory， clarifying the essence of DN in collateral diseases and emphasizing the importance of collateral drugs and microscopic syndrome differentiation in screening target drugs for DN to explore the underlying mechanism of collateral drugs in the treatment of DN， so as to provide evidence for the clinical application of collateral diseases theory and Chinese medicinal prescriptions against collateral diseases in the treatment of DN.

Ligustroflavone ameliorates CCl / 中国天然药物

Liver fibrosis is a pathological process characterized by excess deposition of extracellular matrix (ECM) that are mainly derived from activated hepatic stellate cells. Previous studies suggested that ligustroflavone (LF) was an ingredient of Ligustrum lucidum Ait. with activities of anti-inflammation and anti-oxidation. In this study, we investigated whether LF had any effect on liver fibrosis. In our study, we established a mouse model of carbon tetrachloride (CCl

Application research of entropy weight-based grey systematic theory in quality evaluation of Angelicae Sinensis Radix slices / 中国中药杂志

In order to discuss the "entropy weight method" for weighting various indicators in the comprehensive evaluation of Angelicae Sinensis Radix slices(ASR), the quality of ASR was comprehensively evaluated by entropy weight-based gray systematic theory and cluster analysis. In this study, the contents of ferulic acid, volatile oil, polysaccharide, alcohol extract, water extract, moisture, total ash and acid-insoluble ash in 44 batches of ASR from different sources were determined. The entropy weight method was used for objective weighting. With relative correlation(r_i) as a measure, a multi-index comprehensive evaluation model was constructed for the quality of ASR. The results showed that the relative correlation value of 44 batches of ASR ranged from 0.301 9 to 0.662 9. There were certain differences in the quality of ASR from different sources. The ASR S1-S8, traceable and standardized in processing techno-logy, showed a high relative correlation degree and high quality ranking, indicating that the implementation of systemic management of the production chain of Chinese herbal pieces was beneficial to the quality control of ASR. The quality evaluation results of 44 batches of ASR were consistent with those of traditional geo-authentic habitats for ASR and the mainstream varieties of ASR on market, and basically consistent with the results of cluster analysis. This study suggests that the gray systematic theory based on the entropy weighting method can be used for the quality evaluation of ASR. The objective weighting of the entropy weight method improves the reliability of the gray correlation method and the scientificity of ASR quality evaluation.

Embelin Reverses the Multi-drug Resistance of K562/D to Daunorubicin Independently of P-gp and MDR1 mRNA / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of reversing drug resistance of K562/D cells to daunorubicin by Embelin and its relationship with P-gp and MDR1 mRNA.</p><p><b>METHODS</b>MTT assay was used to detect and compare the cell proliferation rate of treating with DNR alone and DNR combined with Embelin. Flow cytometry with Annexin V-FITC/PI double staining was used to detect cell apoptosis rate, Western blot was used to detect the expression of XIAP,Caspase-3,BCL-2,BAX and P-gp of K562/D cells after using DNR alone and combining with Embelin. Quantitative real-time PCR was used to detect XIAP,BCL-2,BAX and MDR1 mRNA.</p><p><b>RESULTS</b>The ICof K562 and K562/D cells treated with DNR for 24 h were 2.177 µg/ml and 69.43 µg/ml, respectively. The drug-resistance index was 31.89; The proliferation inhibition rates of K562/D cells treated with Embelin of 3, 10, 30, 100 and 300 µg/ml for 24 h were 2.70%±1.08%, 10.92%±4.89%, 28.13%±2.09%, 36.56%±3.24% and 43.59%±1.16%; The proliferation inhibition rates of K562/D cells treated with DNR of 0.1, 1, 10 and 100 µg/ml combined with 10 µg/ml Embelin for 24 h were 31.92%±3.29%, 49.57%±6.87%, 55.16%±0.78% and 71.94%±3.89%. The ICwas 2.11 µg/ml respectively. The reverse index was 32.91. The apoptosis rates of K562/D cells treated with 0.1 µg/ml DNR alone or combined with Embelin of 10 µg/ml and 30 µg/ml for 24 h were 12.06%±0.95%, 27.54%±0.59% and 39.59%±1.57%, respectively. The results of Western blot showed that after combination of DNR with Embelin, the expression of Caspase-3 was significantly down-regulated (P<0.05), moreover, the prolifiration inhibition effect of drug combination on cells could be countreacted by Z-VAD-FMK, at the same time the expression of XIAP and BCL-2 protein was significantly down-regulated(P<0.05), the expression of BAX protein was significantly up-regulated(P<0.05), while there was no change of P-gp expression later (P<0.05). The results of RT-PCR showed that after combination of DNR with Embelin, expression of XIAP and BCL-2 mRNA was significantly down-regulated(P<0.05), expression of BAX mRNA was significantly up-regulated(P<0.05), while there was no obvious change of MDR1 mRNA expression(P>0.05).</p><p><b>CONCLUSION</b>The down-regulation of XIAP contributes to enhance the effect of DNR on K562/D cells, the mechanism of Embelin-reversing the drug-resistence of K562/D cells to DNR does not relate with P-gp and MDR1 mRNA.</p>

Therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer

OBJECTIVE@#To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer.@*METHODS@#A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid (24 rats with sham operation served as sham operation group), and were randomly divided into model group (n = 30), western medicine group (n = 30), traditional Chinese medicine (TCM) group (n = 24) and combination group (combined western medicine and TCM group, n = 30). Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon; TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon. Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed. Twenty-eight days after gavage, interleukin (IL)-1β was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group.@*RESULTS@#Compared with model group and western medicine group, treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer, and increase the healing rate and inhibition rate of peptic ulcer. After IL-1β-induced ulcer recurrence, combination group was significantly superior to model group and western medicine group in ulcer recurrent rate [50% (3/6) vs. 100% (6/6)] and severity.@*CONCLUSIONS@#Basic acid-suppression therapy combined with Qi-Replenishing and Blood-Activating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence.

Therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer

Objective: To explore the therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer. Methods: A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid (24 rats with sham operation served as sham operation group), and were randomly divided into model group (n = 30), western medicine group (n = 30), traditional Chinese medicine (TCM) group (n = 24) and combination group (combined western medicine and TCM group, n = 30). Western medicine group was gavaged with omeprazole in the morning and with iso-volumetric distilled water in the afternoon; TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood-Activating Formula in the afternoon; sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon. Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed. Twenty-eight days after gavage, interleukin (IL)-1β was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group. Results: Compared with model group and western medicine group, treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer, and increase the healing rate and inhibition rate of peptic ulcer. After IL-1β-induced ulcer recurrence, combination group was significantly superior to model group and western medicine group in ulcer recurrent rate [50% (3/6) vs. 100% (6/6)] and severity. Conclusions: Basic acid-suppression therapy combined with Qi-Replenishing and Blood-Activating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence.

Two new triterpenoid glycosides from leaves of Ilex latifolia / 中国中药杂志

Two new triterpenoid glycosides, latifolosides R and S (1 and 2), were isolated from the leaves of Ilex latifolia by various column chromatographic methods. Their structures were elucidated based on NMR spectroscopic data and chemical evidence.

Latest advances of research on autophagy and leukemia treatment / 中国实验血液学杂志

Autophagy, as a conservative self-degradative approach of eukaryotic cells, plays an important role in cellular growth, proliferation,differentiation, death and keeping intracellular steady state. On one hand, autophagy can protect tumor cells to keep survival; on the other hand, autophagy can lead to apoptosis of leukemia cells. The double-edged impacts of autophagy make it to be the hotspot for research on mechanism and treatment of leukemia. This article reviews the diverse effects of autophagy in different leukemia cell lines, as well as its corresponding mechanism resulting in drug resistance, so as to provide theoretic guide for direct rational application of drugs according to their various mechnisms.

A new flavone C-glycoside from leaves of Lophatherum gracile / 中国中药杂志

Several kinds of column chromatography method were used to investigate the chemical constituents of the leaves of Lophatherum gracile. The structures of the isolated compounds were identified based on their physicochemical properties and spectral data. A new flavone C-glycoside was isolated and its structure was identified as 3'-methoxyl-luteolin 6-C-beta-D-galactopyranosiduronic acid (1 --> 2) -alpha-L-arabinopyranoside (1).

A new chromone glycoside from roots of Polygonum multiflorum / 中国中药杂志

Several kinds of column chromatography methods were used to investigate the chemical constituents of roots of Polygonum multiflorum. The structures of the isolated compounds were identified based on their physicochemical properties, spectral data and chemical methods. A new chromone glycoside was isolated and its structure was identified as (S)-2-(2'-hydroxypropyl)-5-methyl7-hydroxychromone-7-0-alpha-L-fucopyranosyl (1-->2)-beta-D-glucopyranoside (1).

Identification of origins of marker chromosomes using fluorescence in situ hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of fluorescence in situ hybridization (FISH) and bacterial artificial chromosome FISH (BAC-FISH) for the diagnosis for patients with marker chromosomes.</p><p><b>METHODS</b>Sixteen patients with marker chromosomes were analyzed with technologies including GTG-banding, Q-banding, multiplex FISH and BAC-FISH.</p><p><b>RESULTS</b>The marker chromosomes in the 16 patients were verified as der(Y) (2 cases), psu dic(Y) (1 case), psu dic(15) (1 case), dic(15) (1 case), del(Y) (1 case), r(X) (5 cases), i(14 or 22) (2 cases), i(18) (1 case).</p><p><b>CONCLUSION</b>FISH and BAC-FISH can both verify the origin of marker chromosomes and provide accurate information for the diagnosis and treatment of patients.</p>

The clinical study of percutaneous transhepatic radiofrequency ablation combined with tumor edge of percutaneous absolute ethanol injection on liver cancer adjacent to major blood vessels / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the effects of percutaneous transhepatic radiofrequency ablation (PRFA) combined with tumor edge of percutaneous absolute ethanol injection (PEI) on liver cancer adjacent to major blood vessels.</p><p><b>METHODS</b>Seventy five patients with liver cancer adjacent to major blood vessels were randomly divided into two groups: PRFA+PEI therapy group (38 cases) and PRFA control group (37 cases). Tumor necrosis rate, AFP levels, local recurrence rate, median for survival time and cum survival were used as the evaluation index to evaluate the efficacies of the two methods.</p><p><b>RESULTS</b>Tumor necrosis rates of the therapy group and the control group were 84.2% and 54.1% (P < 0.01), respectively; AFP levels of therapy group and control group at 1, 3, 6 and 12 months after treatment were (105.0 ± 35.5) μg/L, (28.4 ± 4.3) μg/L, (58.6 ± 6.7) μg/L, (89.5 ± 12.5) μg/L and (137.2 ± 34.6) μg/L, (84.2 ± 18.4) μg/L, (106.6 ± 20.3) μg/L, (173.7 ± 32.0) μg/L, respectively. The rates of therapy group was significantly lower than of control group. Local recurrence rates of the therapy group and control group were 2.6%, 7.9%, 13.2% and 31.6% vs 10.8%, 21.6% , 40.5% and 62.1% (P < 0.05) at 3, 6, 12 and 24 months after treatment, respectively. Median for survival time of the therapy group and control group were 28.0 ± 2.8 months and 19.0 ± 3.6 months, respectively. Cum survival of the therapy group and control group were 84.2%, 78.9%, 60.5% and 31.6% vs 78.4%, 67.6%, 37.8% and 8.1% (P < 0.05) at 6, 12, 24 and 36 months after treatment, respectively.</p><p><b>CONCLUSION</b>PEI as a supplementary treatment of PRFA can effectively improve the treatment of liver cancer adjacent to major blood vessels and significantly reduce the local recurrence rate and improve long-term survival rates.</p>

Total laparoscopic radical trachelectomy with ascending branches of uterine arteries preservation / 中华医学杂志(英文版)

Radical trachelectomy (RT) is a fertility-sparing treatment for young women with early-stage cervical cancer. We report here a case of a 30-year-old nulliparous woman who presented with stage IA2 cervical squamous cancer. She was treated with total laparoscopic radical trachelectomy (TLRT) and laparoscopic pelvic lymphadenectomy (LPL). During this procedure, the ascending branches of uterine arteries were preserved. No metastasis was identified after fourteen months of follow-up. The menstrual pattern normalized and the patient has been attempting to conceive for two months. TLRT might be a safe fertility-preserving procedure for early-stage cervical cancer, due to its minimally invasive nature and shorter recovery time. However, more data are required on recurrence rate, fertility rate and pregnancy outcome in order to fully evaluate the therapeutic efficacy of TLRT.

Influence of hinge position on the effectiveness of open-door expansive laminoplasty for cervical spondylotic myelopathy / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To assess the influence of different hinge positions on clinical results of expansive open-door laminoplasty (EOLP) for cervical spondylotic myelopathy (CSM).</p><p><b>METHODS</b>A total of 102 CSM patients who underwent EOLP from February 2006 to February 2007 were enrolled in this randomized controlled trial. Using a random digits table, 57 patients with the hinge located at the inner margin of the lateral mass were classified as wide-open group, while 45 patients with the hinge positioned at the lamina margin served as narrow-open group. All patients were observed over 24 months, and the clinical and radiological results were analyzed statistically.</p><p><b>RESULTS</b>There were no significant differences in operation duration, intraoperative bleeding volume, Japanese Orthopaedic Association (JOA) scores, cervical curvature index, range of motion and neural function recovery rate. The neural functions were satisfactorily improved after surgery in both groups, while the severity of axial symptoms was significantly lower in the narrow-open group than in the wide-open group (P equal to 0.003). The incidence of C(5) palsy in the wide-open group was higher than that in the narrow-open group (5.3% vs 0), even though the difference did not reach statistical significance (one tailed Fisher's exact test, P equal to 0.17).</p><p><b>CONCLUSIONS</b>Proper inward shift of the hinge can ensure effectiveness of surgical decompression, avoid an excessive backward shift of the spinal cord, decrease the incidence of C(5) palsy and alleviate the severity of axial symptoms.</p>

Clinical validity of hinge position to expansive semi open-door laminoplasty / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate and compare the efficacy and clinical results of cervical expansive open door laminoplasty (EOLP) with different hinge position.</p><p><b>METHODS</b>From February 2006 to February 2007, a total of 102 cases with cervical spondylotic myelopathy were assessed in this randomized controlled trial. Fifty-seven patients underwent EOLP with the hinge located at the inner margin of the lateral mass classified as wide-open group. Forty-five cases who underwent EOLP with the hinge positioned at the lamina margin served as narrow-open group. The clinical results and radiological examinations of both groups were evaluated 24 months after surgery.</p><p><b>RESULTS</b>There were no significant differences in operation time, bleeding quantity and recovery rate of Japanese Orthopaedic Association (JOA) scores. The incidence of C(5) palsy and severity of axial symptoms in the wide-open group were significantly lower than those in the narrow-open group (P < 0.05). There were no significant differences in cervical curvature index and range of motion between the two groups.</p><p><b>CONCLUSIONS</b>Well-suited and appropriated inwardly shift the hinge could promote clinical outcomes after EOLP, especially decrease the incidence of the C(5) palsy and the severity of axial symptom, but it is contraindication for patients with ossification of posterior longitudinal ligament, ossification of ligament flavum and fluorosis cervical stenosis.</p>

Application of fluorescence in situ hybridization in prenatal diagnosis of complex chromosomal abnormalities / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the application of fluorescence in situ hybridization (FISH) technique in prenatal diagnosis of complex chromosomal abnormalities.</p><p><b>METHODS</b>Eleven prenatal diagnosis cases (8 from amniocentesis and 3 from cord blood) with complex chromosomal abnormalities detected by routine G-banding, were further analyzed by FISH.</p><p><b>RESULTS</b>The FISH technique confirmed the results of balanced chromosome rearrangements detected by G-banding, and clarified the structure of the derivative chromosomes in the 3 amniocentesis samples and the origin of the mark chromosomes in the 2 cord blood samples.</p><p><b>CONCLUSION</b>FISH can be used to diagnose the complex chromosomal abnormalities accurately in prenatal diagnosis, and can provide very useful genetic information for clinical diagnosis and treatment.</p>