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1.
Article in English | WPRIM | ID: wpr-862231

ABSTRACT

@#The recent outbreak of coronavirus disease (COVID-19) has become a major public health issue caused by 2019 novel coronavirus (2019-nCoV).[1] Severe COVID-19 patients may reveal a dysregulated immune response that allows the development of viral hyperinflammation.[2] In the fight against COVID-19, inflammatory parameters towards illness severity should be identified to improve the prognosis of patients. In this study, we aimed to assess the discriminative ability of several inflammation indicators in severe COVID-19 infection.

2.
Article in Chinese | WPRIM | ID: wpr-885976

ABSTRACT

Objective: To observe the effect of electroacupuncture (EA) pretreatment on the protein expression of c-fos in fastigial nucleus (FN) and lateral hypothalamus area (LHA) in rats with acute myocardial ischemia-reperfusion injury (MIRI), and to explore the role and mechanism of FN and LHA in EA at the Heart Meridian fighting against acute MIRI reaction. Methods: Seventy Sprague-Dawley rats were randomly divided into a sham operation group, a model group, an EA-Heart Meridian group and an EA-Lung Meridian group, with 14 rats in each group; an LHA lesion plus EA-Heart Meridian group (LHA+EA-Heart Meridian group) and a FN lesion plus EA-Heart Meridian group (FN+EA-Heart Meridian group), with 7 rats in each group. Except the sham operation group, the left anterior descending branch of coronary artery was ligated to establish acute MIRI rat models in the other 5 groups. In the three groups with EA-Heart Meridian treatment, Shenmen (HT 7) and Tongli (HT 5) were selected; Taiyuan (LU 9) and Lieque (LU 7) were selected in the EA-Lung Meridian group. All the EA groups received EA stimulation prior to modeling, with 1 mA in current intensity and 2 Hz in frequency, 20 min each time, once a day for a total of 7 d. The sham operation group and the model group did not receive EA stimulation. The electrocardiogram was observed in the rats to analyze the ST-segment deviation and cardiac arrhythmia score. The expression of c-fos protein in FN and LHA was detected by immunohistochemistry method. Results: Compared with the sham operation group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in the FN and LHA increased significantly in the model group (all P<0.05). Compared with the model group, the ST-segment deviation, cardiac arrhythmia score and the expression of c-fos protein in FN and LHA decreased significantly in the EA-Heart Meridian group (all P<0.05). Compared with the EA-Heart Meridian group, the ST-segment deviation and cardiac arrhythmia score increased significantly in the EA-Lung Meridian group, LHA+EA-Heart Meridian group and FN+EA-Heart Meridian group (all P<0.05); the expression of c-fos in FN increased significantly in the EA-Lung Meridian group and LHA+EA-Heart Meridian group (both P<0.05); the expression of c-fos in LHA increased significantly in the EA-Lung Meridian group and FN+EA-Heart Meridian group (both P<0.05). Conclusion: FN and LHA are involved in the mechanism of EA at Heart Meridian to improve the acute MIRI reactions, and the cerebellum may participate in the improvement of cardiac function by EA through the cerebellum-hypothalamus projection.

3.
Article in English | WPRIM | ID: wpr-881063

ABSTRACT

Paris saponin VII (PSVII), a bioactive constituent extracted from Trillium tschonoskii Maxim., is cytotoxic to several cancer types. This study was designed to explore whether PSVII prevents non-small-cell lung cancer (NSCLC) proliferation and to investigate its molecular target. AMP-activated protein kinase (AMPK) has been implicated in the activation of autophagy in distinct tissues. In cultured human NSCLC cell lines, PSVII induces autophagy by activating AMPK and inhibiting mTOR signaling. Furthermore, PSVII-induced autophagy activation was reversed by the AMPK inhibitor compound C. Computational docking analysis showed that PSVII directly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation. Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSVII and AMPK. In summary, PSVII acts as a direct AMPK activator to induce cell autophagy, which inhibits the growth of NSCLC cells. In the future, PSVII therapy should be applied to treat patients with NSCLC.

4.
Asian Journal of Andrology ; (6): 69-73, 2021.
Article in English | WPRIM | ID: wpr-879738

ABSTRACT

46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with/without the presence of Müllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (AR), steroid 5-alpha-reductase 2 (SRD5A2) and nuclear receptor subfamily 5 Group A member 1 (NR5A1) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR, SRD5A2, and NR5A1 genes were the most common pathogenic genes in our cohort.

5.
Chinese Medical Journal ; (24): 1064-1069, 2021.
Article in English | WPRIM | ID: wpr-878160

ABSTRACT

BACKGROUND@#Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).@*METHODS@#The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.@*RESULTS@#The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.@*CONCLUSION@#Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.


Subject(s)
Lipid Metabolism/genetics , Mendelian Randomization Analysis , Thyroid Function Tests , Thyroid Gland , Thyrotropin , Thyroxine , Triiodothyronine
6.
Article in Chinese | WPRIM | ID: wpr-877651

ABSTRACT

OBJECTIVE@#To observe the effect of electroacupuncture (EA) preconditioning at heart meridian acupoints on the contents of dopamine (DA) and 5-hydroxytryptamine (5-HT) in lateral hypothalamus area (LHA) and cerebellar fastigial nucleus (FN) in the rats with acute myocardial ischemia-reperfusion injury (MIRI), and explore the role and mechanism of LHA and FN in the effect of EA at heart meridian acupoints against acute MIRI.@*METHODS@#Sixty SD rats were randomly divided into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 12 rats in each group, as well as an LHA plus heart meridian group (damage of bilateral LHA) and an FN plus heart meridian group (damage of bilateral FN), 6 rats in each one. Three days after nucleus destruction, EA was applied to "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA heart meridian group, the LHA plus heart meridian group and the FN plus heart meridian group and EA was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7) in the EA lung meridian group, with 1 V in stimulating voltage and 2 Hz in frequency, lasting 20 minutes each time, once a day, for consecutively 7 days before model replication. Except in the sham-operation group, MIRI rat models were duplicated by ligation of the left anterior descending branch of the coronary artery in the rest groups. Using Power lab physiological recorder, ST segment displacement value was recorded before modeling, 30 min after ligation and 120 min after reperfusion separately. The high performance liquid chromatography-electrochemical detection and analysis system was adopted to determine the contents of DA and 5-HT in LHA and FN dialysate after rat modeling in each group.@*RESULTS@#In comparison of ST segment displacement value 30 min after ligation and 120 min after reperfusion among groups, the value in the model group was higher than that in the sham-operation group (@*CONCLUSION@#EA preconditioning at heart meridian acupoints can effectively alleviate myocardial injury in acute MIRI rats, during which, DA and 5-HT in LHA and FN may be the important material basis.


Subject(s)
Acupuncture Points , Animals , Cerebellar Nuclei , Dopamine , Electroacupuncture , Hypothalamic Area, Lateral , Myocardial Ischemia , Myocardial Reperfusion Injury/therapy , Rats , Rats, Sprague-Dawley , Serotonin
7.
Article in Chinese | WPRIM | ID: wpr-877555

ABSTRACT

To explore the implementation path of the ideological and political education according to the characteristics of teaching sections in acupuncture-moxibustion courses. Excavating the traditional Chinese culture and medical ethics contained in acupuncture-moxibustion courses helps strengthening the ideological and political quality of medical students and noble medical ethics, strengthening self-confidence in both professions and culture, and also helps students establishing a correct outlook on life, world and value. The moral education integrated with the professional teaching will helps explore ideological and political education path in acupuncture-moxibustion courses, so as to solidify them into each teaching sections and improve the teaching effect.


Subject(s)
Acupuncture , Acupuncture Therapy , Humans , Moxibustion , Students
8.
Acta Pharmaceutica Sinica ; (12): 538-544, 2021.
Article in Chinese | WPRIM | ID: wpr-873758

ABSTRACT

M701 is a bispecific CD3/EpCAM T-cell engager antibody for the treatment of malignant ascites. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe and predict the antitumor effect of M701 in human colorectal cancer xenograft mice. We developed the M701 PK model based on plasma concentration data after i.v. administration. A tumor growth model for human colorectal cancer xenograft was developed to evaluate the antitumor effect of M701. We additionally simulated the inhibitory effect of M701 on tumor volume under different dose regimens based on a PK/PD model. A two-compartment model was developed to predict the PK in human colorectal cancer xenograft mice. The relationship between the M701 concentration and tumor growth inhibition was characterized by a combined Simeoni tumor growth/transit compartment model. The estimated pharmacodynamic parameters were related to the tumor growth characteristics λ0 (0.212 d-1) and λ1 (0.044 7 cm3·d-1), to the drug potency k2 (0.071 5 mL·ng-1·d-1), and to the kinetics of tumor cell death k1 (2×10-5 d-1). A model visual predictive check showed that both the PK model and the tumor growth model closely fit the observed data. Simulated tumor growth after administration of M701 (0.5 mg·kg-1 every 6 days and 0.25 mg·kg-1 every 3 days) could be effectively inhibited. This population PK/PD model of M701 provides insight into the antitumor effect of M701 and supports the further therapeutic development of M701.

9.
Article in Chinese | WPRIM | ID: wpr-873747

ABSTRACT

Objective To investigate the epidemiological profiles of echinococcosis cases reported in non-endemic areas of China in the National Notifiable Disease Report System from 2004 to 2016, so as to provide insights into the development of effective surveillance and response measures. Methods The data pertaining to the echinococcosis cases reported in the National Notifiable Disease Report System in 22 non-endemic provinces of China from 2004 to 2016 were collected, and the epidemiological profiles of the reported echinococcosis cases were descriptively analyzed. Results A total of 462 echinococcosis cases were reported in the 22 non-endemic provinces of China from 2004 to 2016, and the number of reported cases increased with time (χ2 = 4.516, P = 0.034). During the 13-year period from 2004 to 2016, the highest number of echinococcosis cases was reported in central and eastern China (56.49%), followed by in northern and northeastern China (30.30%), and the highest number of echinococcosis cases was reported in Henan Province (99 cases). Among the 462 echinococcosis cases reported, there were 234 men and 228 women, and the mean age was (41.42 ± 16.03) years (range, 4 to 86 years), with the highest number of echinococcosis cases reported at ages of 20 to 50 years (63.20%). The highest proportion of occupations was farmers and herdsmen (36.15%), and the greatest source was from echinococcosis-endemic provinces (50.43%); in addition, 97.40% of the echinococcosis cases were reported by hospitals. Conclusions Echinococcosis cases were reported in all 22 non-endemic provinces of China in the National Notifiable Disease Report System from 2004 to 2016, and the number of reported cases appeared an overall tendency for sporadicity and local increase with time. Screening of echinococcosis is recommended among famers and herdsmen at ages of 20 to 50 years from endemic regions by medical institutions in non-endemic regions for timely identification and treatment of echinococcosis cases.

10.
Article in Chinese | WPRIM | ID: wpr-787737

ABSTRACT

@#To evaluate the association between the frequency of bowel movement (BMF) and the risk of Parkinson's disease (PD). In this study, 510 134 participants from the China Kadoorie Biobank (CKB) were included after excluding those who reported to had been diagnosed with cancer at baseline survey. The baseline survey was conducted from 2004 to 2008. The study used the data from the baseline survey and follow-up until December 31, 2016. Cox proportional hazards regression models were used to estimate the s and the 95s of risk of PD diagnosis with BMF. During an average follow-up period of (9.9±1.9) years, 808 participants were diagnosed with PD. Compared with participants who had bowel movements every day, the multivariable-adjusted (95) for those who had bowel movements<3 times/week, once every 2-3 days, and>1 time/day were 3.62 (2.88-4.54), 2.13 (1.74-2.60), and 0.81 (0.63-1.05), respectively. The linear trend test results of the association between BMF and risk of PD diagnosis was significant (<0.001). Compared with the participants who had bowel movements ≥1 time/day, the multivariable-adjusted (95) for those who had bowel movements<1 time/day was 3.13 (2.32-4.23) within the 5 years of follow- up and was 2.48 (2.05-3.01) beyond the 5 years of follow-up. The gender specific results were similar. The association of BMF<1 time/day with risk of PD diagnosis was stronger in older participants. The participants with low BMF at baseline survey would have higher risk for PD diagnosis in the subsequent 10 years on average. Since abnormal decrease of BMF is easy to be found, programs could be set up for the early screening of PD in older people, along with other early symptoms of PD.

11.
Acta Pharmaceutica Sinica B ; (6): 123-135, 2020.
Article in English | WPRIM | ID: wpr-781546

ABSTRACT

We examined the impact of gut inflammation on the expression of cytochrome P450 (P450) and other biotransformation genes in male mice using a dextran sulfate sodium (DSS)-induced colitis model. Several P450 isoforms, including CYP1A, CYP2B, CYP2C, and CYP3A, were down-regulated, accompanied by decreases in microsomal metabolism of diclofenac and nifedipine, in the liver and small intestine. The impact of the colitis on clearance of oral drugs varied for four different drugs tested: a small decrease for nifedipine, a relatively large decrease for lovastatin, but no change for pravastatin, and a large decrease in the absorption of cyclosporine A. To further assess the scope of influence of gut inflammation on gene expression, we performed genome-wide expression analysis using RNA-seq, which showed down-regulation of many CYPs, non-CYP phase-I enzymes, phase-II enzymes and transporters, and up-regulation of many other members of these gene families, in both liver and intestine of adult C57BL/6 mice, by DSS-induced colitis. Overall, our results indicate that gut inflammation suppresses the expression of many P450s and other biotransformation genes in the intestine and liver, and alters the pharmacokinetics for some but not all drugs, potentially affecting therapeutic efficacy or causing adverse effects in a drug-specific fashion.

12.
Article in English | WPRIM | ID: wpr-781415

ABSTRACT

Objective@#To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes.@*Methods@#Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed.@*Results@#A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( ): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% : -1.60, -1.09), -1.10 kg/m (95% : -1.42, -0.78), and -1.28 cm (95% : -1.69, -0.86), respectively.@*Conclusion@#GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

13.
Article in Chinese | WPRIM | ID: wpr-867978

ABSTRACT

Objective:To investigate the current basic situation of ultrasound machines of ultrasound departments in Shanghai medical institutions, and to provide the basis for making management policy in order to promote medical quality.Methods:Questionnaire surveys about ultrasound machines and service ability including producing countries of ultrasound machines, the number of ultrasound machines, using years of ultrasound machines, yearly workload and the yearly number of patients that each ultrasound machine accepted were made in 2013 and 2018, respectively. Statistical results were compared between the two surveys.Results:Compared with 2013, the share of imported ultrasound machines declined in 2018 (82% vs 91%). Compared with 2013, the number of ultrasound machines in Shanghai medical institutions had increased by 31% in 2018 (2 123 vs 1 617). The occupancy rate of ultrasound machines in tertiary hospitals was the highest (tertiary hospitals 40%, secondary hospitals 25%, primary grade hospitals 20%, and private hospitals 15%). Compared with 2013, the proportion of ultrasound machines that have been used for more than 10 years increased (9% vs 4%), the yearly workload of ultrasound examination had increased by 46% (19.82 million person-time vs 13.59 million person-time). Tertiary hospitals bored the highest proportion of the workload (tertiary hospitals 51%, secondary hospitals 35%, primary grade hospitals 4%, and private hospitals 10%). Currently, the number of ultrasound machines per 10, 000 people in Shanghai was 1.14. The yearly number of patients that each ultrasound machine accepted had increased by 11% (9300 person-time vs 8400 person-time in 2018).Conclusions:The scale of ultrasound departments in Shanghai medical institutions has been developing. Brand localization of ultrasound machines is improving. However, the renewal ability of ultrasound machines still needs to be improved. The workload of ultrasound department is getting heavier. Hierarchical diagnosis and treatment is unbalanced.

14.
Article in Chinese | WPRIM | ID: wpr-862473

ABSTRACT

On the basis of systematic evaluation of 32 provincial capital cities and municipalities in their capacity for preventing and controlling emerging infectious diseases, focus analysis is made on Wuhan in relation to its advantages and disadvantages as follows:There has been a legal basis for epidemic prevention according to law, but it has not translated into effective action.There has been an organizational basis for responding to epidemic, but coordination mechanism has not been effectively established.The management mechanism has been complete, but the division of responsibilities among different departments has not been clear.The monitoring network has been set up, but its role of "predictive warning" has not been played.Insufficiency of public health service delivery was observed owing to lack of financial investment.In cities of China, advantages and disadvantages have been both existent in their capacity to prevent and control of emerging infectious disease.We should be vigilant in this regard. It is imperative to "fill defects, stop leaks and strengthen weakness".There is a Chinese saying:"It is not too late to mend a fold after the sheep have been stolen".

15.
Article in Chinese | WPRIM | ID: wpr-828892

ABSTRACT

OBJECTIVE@#To compare the median effective dose (ED) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery.@*METHODS@#We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 μg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 μg/kg interval. The ED was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min.@*RESULTS@#The ED value of intranasal dexmedetomidine for sedation was 1.84 μg/kg (95% : 1.68-2.00 μg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 μg/kg (95% : 3.21-3.54 μg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects.@*CONCLUSIONS@#In children with acyanotic congenital heart disease, the ED of intranasal dexmedetomidine for TTE sedation increases to 3.38 μg/ kg after cardiac surgery from the preoperative value of 1.84 μg/kg.


Subject(s)
Administration, Intranasal , Cardiac Surgical Procedures , Child , Dexmedetomidine , Heart Defects, Congenital , General Surgery , Humans , Hypnotics and Sedatives
16.
Acta Pharmaceutica Sinica B ; (6): 746-765, 2020.
Article in English | WPRIM | ID: wpr-828845

ABSTRACT

Protein neddylation is a post-translational modification which transfers the ubiquitin-like protein NEDD8 to a lysine residue of the target substrate through a three-step enzymatic cascade. The best-known substrates of neddylation are cullin family proteins, which are the core component of Cullin-RING E3 ubiquitin ligases (CRLs). Given that cullin neddylation is required for CRL activity, and CRLs control the turn-over of a variety of key signal proteins and are often abnormally activated in cancers, targeting neddylation becomes a promising approach for discovery of novel anti-cancer therapeutics. In the past decade, we have witnessed significant progress in the field of protein neddylation from preclinical target validation, to drug screening, then to the clinical trials of neddylation inhibitors. In this review, we first briefly introduced the nature of protein neddylation and the regulation of neddylation cascade, followed by a summary of all reported chemical inhibitors of neddylation enzymes. We then discussed the structure-based targeting of protein-protein interaction in neddylation cascade, and finally the available approaches for the discovery of new neddylation inhibitors. This review will provide a focused, up-to-date and yet comprehensive overview on the discovery effort of neddylation inhibitors.

17.
Article in Chinese | WPRIM | ID: wpr-828529

ABSTRACT

Cullin-RING E3 ligases (CRLs) are the major components of ubiquitin-proteasome system, responsible for ubiquitylation and subsequent degradation of thousands of cellular proteins. CRLs play vital roles in the regulation of multiple cellular processes, including cell cycle, cell apoptosis, DNA replication, signalling transduction among the others, and are frequently dysregulated in many human cancers. The discovery of specific neddylation inhibitors, represented by MLN4924, has validated CRLs as promising targets for anti-cancer therapies with a growing market. Recent studies have focused on the discovery of the CRLs inhibitors by a variety of approaches, including high through-put screen, virtual screen or structure-based drug design. The field is, however, still facing the major challenging, since CRLs are a large multi-unit protein family without typical active pockets to facilitate the drug design, and enzymatic activity is mainly dependent on undruggable protein-protein interactions and dynamic conformation changes. Up to now, most reported CRLs inhibitors are aiming at targeting the F-box family proteins (e.g., SKP2, β-TrCP and FBXW7), the substrate recognition subunit of SCF E3 ligases. Other studies reported few small molecule inhibitors targeting the UBE2M-DCN1 interaction, which specifically inhibits CRL3/CRL1 by blocking the cullin neddylation. On the other hand, several CRL activators have been reported, such as plant auxin and immunomodulatory imide drugs, thalidomide. Finally, proteolysis-targeting chimeras (PROTACs) has emerged as a new technology in the field of drug discovery, specifically targeting the undruggable protein-protein interaction. The technique connects the small molecule that selectively binds to a target protein to a CRL E3 via a chemical linker to trigger the degradation of target protein. The PROTAC has become a hotspot in the field of E3-ligase-based anti-cancer drug discovery.


Subject(s)
Antineoplastic Agents , Pharmacology , Therapeutic Uses , Drug Design , Drug Discovery , Enzyme Inhibitors , Pharmacology , Therapeutic Uses , Humans , Neoplasms , Ubiquitin-Protein Ligases , Metabolism , Ubiquitination
18.
Article in Chinese | WPRIM | ID: wpr-828446

ABSTRACT

This study is a randomized controlled trial of Reyanning Mixture in the treatment of acute tonsillitis. According to the ratio of 1∶1∶1, a total of 144 patients were randomly divided into Reyanning Mixture group(RYN), Reyanning Mixture+Amoxicillin Capsules group(RYN+Amoxil) and Amoxicillin Capsules group(Amoxil), with 48 cases in each group, in order to evaluate the efficacy and safety of RYN alone or combined with Amoxil in the treatment of acute tonsillitis, and provided high-quality evidences for treatment of infectious diseases with traditional Chinese medicine and reduced use of antibiotics. The dosage of RYN was 20 mL, 3 times a day, 100 mL/bottle, oral for 7 days, and Amoxil dosage was 0.5 g, 3 times a day, 0.5 g×12 tablets/plate, oral for 7 days. A total of 144 cases were included, 3 cases were excluded(1 case was mistakenly included, 2 cases did not take drugs after inclu-ded), and a total of 141 cases were included in the full analysis set(FAS). The results showed statistical differences in the recovery time of the disease, the disappearance rate of fever on the 3 rd day and the disappearance rate of tonsillar redness and swelling between RYN and Amoxil. There were statistical differences in the cure rate of disease, recovery time of disease, body temperature recovery time, fever disappearance rate on the 3 rd day, pharynx swelling and pain disappearance rate and tonsil swelling disappearance rate between the RYN+Amoxil and Amoxil, but with no significant difference in the above aspects compared with RYN. The DDD of antibiotic use in RYN+Amoxil was significantly lower than that in Amoxil(P<0.01). According to the findings, when RYN was used alone in the treatment of acute tonsillitis, it was superior to Amoxil in time of recovery, short-term improvement of fever and redness and swelling of tonsil. Compared with RYN+Amoxil, there was no difference in cure rate of disease, recovery time of disease, body temperature recovery time, short-term improvement of fever, swelling of pharynx and swelling of tonsil, with a better efficacy than Amoxil. The clinical effect of RYN was similar to that of combined Amoxil in the treatment of acute tonsillitis, and RYN was superior to Amoxil in the time of recovery, short-term improvement of fever and redness and swelling of tonsil, with no adverse event or adverse reaction. RYN+Amoxil can significantly reduce the DDD value of antibiotics in the treatment of acute tonsillitis, with significant clinical advantages over Amoxil.


Subject(s)
Anti-Bacterial Agents , Therapeutic Uses , Double-Blind Method , Drugs, Chinese Herbal , Fever , Drug Therapy , Humans , Tonsillitis , Drug Therapy
19.
Article in Chinese | WPRIM | ID: wpr-878856

ABSTRACT

Based on the results of the fourth national survey of traditional Chinese medicine resources in Turpan city, Xinjiang, this study counted the types of traditional Chinese medicine resources in Turpan Basin. The spatial distribution differences of traditional Chinese medicine resources in Turpan Basin of Xinjiang were analyzed by using grid technology, trend surface analysis, global spatial autocorrelation analysis, and local spatial autocorrelation analysis, so as to clarify the overall change trend and aggregation degree of traditional Chinese medicine resources in Turpan Basin in horizontal and vertical directions. The results showed the following: in the horizontal direction, the species richness of traditional Chinese medicine resources in the central part of Turpan Basin was high, and there were great differences in the species richness of traditional Chinese medicine resources in Turpan Basin under different grid sizes. The spatial scale effect of the richness of traditional Chinese medicine resources in Turpan Basin is obvious. Among them, under the 30 km×30 km scale, the richness of the types of Chinese medicine resources shows a high spatial correlation, and the richness of the types of Chinese medicine resources at 5 km×5 km scale presents a near random distribution state, and the richness of the types of Chinese medicine resources at 80, 90, and 100 km scale sits negatively related. Vertical direction, Chinese medicine resources appear rich at the range of-154-150 m and 900-1 050 m following by range of 1 050-1 200 m.


Subject(s)
China , Medicine, Chinese Traditional , Spatial Analysis , Technology
20.
Chinese Acupuncture & Moxibustion ; (12): 1211-1216, 2020.
Article in Chinese | WPRIM | ID: wpr-877588

ABSTRACT

OBJECTIVE@#To observe the effect of moxibustion on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin protein (PI3K/Akt/mTOR) signaling pathway in the foot-pad synovial tissue in rats with rheumatoid arthritis (RA), and to explore the mechanism of moxibustion for treating RA.@*METHODS@#Forty healthy SD rats were randomly divided into a control group, a model group, a moxibustion group, a cigarette-moxibustion group and a medication group, 8 rats in each group. The RA model was established with subcutaneous injection of complete Freund's adjuvant (CFA) in the left hind foot-pad under wind, cold and wet environment in the model group, the moxibustion group, the cigarette-moxibustion group and the medication group. The rats in the moxibustion group were treated with moxibustion at "Zusanli" (ST 36) for 20 min; the rats in the cigarette-moxibustion group were treated with moxibustion of ordinary cigarette at "Zusanli" (ST 36) for 20 min; the rats in the medication group were treated with tripterygium glycosides suspension (0.8 mg/100 g) by gavage. All the intervention was given once a day for 15 days. The left hind foot-pad volume was measured before and after modeling and after 15-day intervention. After 15-day intervention, the serum levels of IL-17 and IL-23 were detected by ELISA method, and the expression levels of PI3K, Akt and mTOR in synovial tissue of left hind foot-pad were detected by Western blot method.@*RESULTS@#The volume of left hind foot-pad, the serum levels of IL-23 and IL-17 and the expression of PI3K, Akt and mTOR in synovial tissue of left hind foot-pad in the model group were higher than those in the control group (@*CONCLUSION@#Moxibustion may play a therapeutic effect on RA by inhibiting the level of IL-23, IL-17 and the activity PI3K/Akt/mTOR, and regulating inflammatory response and autophagy.


Subject(s)
Animals , Arthritis, Rheumatoid/therapy , Moxibustion , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Rats , Rats, Sprague-Dawley , Signal Transduction , Synovial Membrane , TOR Serine-Threonine Kinases
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