Objective: To study the therapeutic effect of Fumaderm® in Freund's complete adjuvant-induced arthritis (AIA) in Spraque-Dawley rats. Methods: Adjuvant-induced arthritis (AIA) was established by intradermal injection of 0.1 mL of Freund's complete adjuvant (CFA) in the palmar surface of the right hindpaw and Fumaderm® was delivered by oral gavage for 28 days. After CFA injection, the edema of the hindpaw was determined every two days. On 28 days after CFA injection, the lymphocyte subsets of peripheral blood and the cytokines were determined by flow cytometry, meanwhile the histopathological examination of ankle-joints of the animals was performed. Results: Fumaderm® had a significant therapeutic effect on AIA. The hindpaw swelling was reduced significantly in a dose-dependent manner. The ratio of peripheral blood T lymphocytes was improved obviously. Multiparameter cytokine analysis from peripheral blood CD4+ T cells showed a decrease of proinflammatory cytokines and an increase of anti-inflammatory cytokines in Fumaderm® treated animals. A strongly reduced inflammatory response in the joint synovium was observed. Conclusion: Fumaderm® has potential anti-inflammatory effects on AIA rats. Further investigation is needed to elucidate the molecular mechanism involved in the clinical effect observed in the AIA model.

Objective: To study the therapeutic effect of Fumaderm® in Freund's complete adjuvant-induced arthritis (AIA) in Spraque-Dawley rats. Methods: Adjuvant-induced arthritis (AIA) was established by intradermal injection of 0.1 mL of Freund's complete adjuvant (CFA) in the palmar surface of the right hindpaw and Fumaderm® was delivered by oral gavage for 28 days. After CFA injection, the edema of the hindpaw was determined every two days. On 28 days after CFA injection, the lymphocyte subsets of peripheral blood and the cytokines were determined by flow cytometry, meanwhile the histopathological examination of ankle-joints of the animals was performed. Results: Fumaderm® had a significant therapeutic effect on AIA. The hindpaw swelling was reduced significantly in a dose-dependent manner. The ratio of peripheral blood T lymphocytes was improved obviously. Multiparameter cytokine analysis from peripheral blood CD4+ T cells showed a decrease of proinflammatory cytokines and an increase of anti-inflammatory cytokines in Fumaderm® treated animals. A strongly reduced inflammatory response in the joint synovium was observed. Conclusion: Fumaderm® has potential anti-inflammatory effects on AIA rats. Further investigation is needed to elucidate the molecular mechanism involved in the clinical effect observed in the AIA model.

K21. The mean t1/2(?) was (2.7?0.4) h, Vd was about 11.18 L?kg-1.The C-T profile conformed to two compartment open model. The plasma Dau concentration-time curves showed a double-peak phenomenon in all dosages of all dogswhen dauricine was given by intragastric was.The tpeak(1) was (0.8?0.6) ～(1.2?0.5) h,tpeak(2) was (5.2?3.2) ～(6.5?1.9)h,Cmax(2) 0.05) and the AUC was increased in proportion.The drug is eliminated non-linearly when the dosage is above 50 mg?kg-1, the parameters t1/2(el),CL, AUC/X0 shows great difference (P

AIMTo study the protective effect of procyanidins from the seedpod of the lotus (LSPC) on myocardial ischemia and reperfusion in rats.

METHODSMyocardial injury model was made by ligating the coronary artery for 30 min followed by reperfusion for 45 min in anesthetized rat and 30 min of ischemia followed by 30 min of reperfusion in the isolated rat heart. All animals were given the medicine or normal saline before the experiment. ET, Ang I, Ang II in the serum, the MDA content, SOD activity, NO level, the recovery rate of coronary flow (CF) and heart rate (HR) after reperfusion and CK, XO from the myocardial cells were observed.

RESULTSLSPC was shown to inhibit the release of ET, Ang II (P < 0.05) , and the increase of MDA content (P < 0.05). It was also found to increase the SOD activity (P < 0.05) and NO level (P < 0.01). LSPC was found to increase the recovery rate of the coronary flow (CF) and heart rate (HR) after reperfusion (P < 0.05 or P < 0.01), decrease the release of CK from the myocardial cells (P < 0.01), depress the XO activity of myocardial tissue (P < 0.05), as well as improve the myocyte ultrastructural pathological injury.

CONCLUSIONThe anti-ischemia effect of LSPC was related to the mechanism of scavenging the oxygen free radicals directly, cutting off the source of free radicals, reducing tissue peroxidation, stabilizing the cells membrane, depressing the production of EDCF and increasing the NO level as well.

Animals ; Biflavonoids ; isolation & purification ; pharmacology ; Cardiotonic Agents ; pharmacology ; Catechin ; isolation & purification ; pharmacology ; Coronary Circulation ; drug effects ; Loteae ; chemistry ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; metabolism ; Myocardium ; enzymology ; ultrastructure ; Proanthocyanidins ; isolation & purification ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVE: To determine the effect of ginsenoside on the cellular proliferation, apoptosis and cell cycles in LC A549 and HUVEC 304 cell lines. METHODS: A549 and HUVEC 304 cell lines were cultured with different concentrations of ginsenoside. Cellular proliferation was detected with MTT, apoptosis and cell cycles were checked with Flow Cytometer, and change of microstructure was observed by transmission electron microscope. RESULTS: The apoptosis rate was 29.8% in A549 cell lines after being interfered with ginsenoside at 3 x 10(-6) mol/L, significantly higher than that in the control group ( P < 0.05). No change was observed in the cell cycles after being interfered with ginsenoside. The inhibitive rate of ginsenoside was 12.53% for HUVEC 304 cell line at 1 x 10(-4) mol/L (P < 0.05 ). The cells induced by conditioned medium could be inhibited by ginsenoside, and apoptotic body could be found in cells induced by conditioned medium at 10(-6) mol/L. CONCLUSION The proliferation of vascular endothelial cell could be inhibited by ginsenoside, and apoptosis could also be found in both tumor cells and cells induced by conditioned medium after being interfered with ginsenoside.
Adenocarcinoma ; pathology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells ; cytology ; Ginsenosides ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Umbilical Veins ; cytology

BACKGROUNDA voluntary procedure for reporting adverse drug reactions (ADRs) was formally put in place in 1989. However, only a small proportion of ADR reports are actually forwarded to the national monitoring center. To identify the reasons for underreporting, the authors investigated the awareness and attitudes of healthcare professionals (doctors, nurses, and administrators) toward the ADR system in China. In addition, the authors sought to formulate approaches to improve the current ADR reporting system.

METHODSStructured interviews were carried out in 16 hospitals selected from 27 municipal hospitals in Wuhan, Hubei Province, China. A questionnaire survey of a stratified random sample of approximately 15% of healthcare professionals in each selected hospital was conducted during February to March 2003.

RESULTSThe response rate of this survey was 85%. One thousand six hundred and fifty-three questionnaires were used in the final analysis. Only 2.7% of the healthcare professionals had a correct understanding to the definition of ADR. Eighty-nine point two percent of the healthcare professionals had encountered ADRs. Ninety-four percent of them were aware of the need to report these to the ADR monitoring center. However, only 28.5% of doctors, 22.8% of nurses, and 29.7% of administrators actually submitted a report. For the most part, they reported ADRs to the hospital pharmacy (66.0%), to other departments in the hospital (72.5%), and to the pharmaceutical industry (23.0%), rather than to the national monitoring center (2.9%) or regional monitoring center (9.5%). Severe or rare ADRs and ADRs to new products were generally perceived to be significant enough to report. Sixty-two point one percent of the healthcare professionals had encountered ADRs, yet not reported them to anybody. The major reasons for not reporting included no knowledge of the reporting procedure (71.4%), unavailability of the reporting center mailing address (67.9%), unavailability of the ADR report form (60.4%), lack of knowledge of the existence of a national ADR reporting system (52.2%), and belief that the ADR in question was already well known (44.1%).

CONCLUSIONSHealthcare professionals in Wuhan, China have little basic knowledge of ADR and of the voluntary reporting system. The main reasons for underreporting were lack of basic knowledge about ADRs and the voluntary reporting procedure. Education and training of healthcare professionals is needed to improve the current ADR reporting system.

Adverse Drug Reaction Reporting Systems ; trends ; Attitude of Health Personnel ; China ; Health Knowledge, Attitudes, Practice ; Hospital Administrators ; Humans ; Interviews as Topic ; Nurses ; Physicians ; Surveys and Questionnaires

OBJECTIVETo investigate the knowledge and attitudes of healthcare professionals (doctors, nurses and administrators) to adverse drug reactions (ADR) in Wuhan city and to identify the reasons for under-reporting.

METHODSStructured interviews were carried out in Wuhan, Hubei province. Questionnaire survey to approximately 15% of the medical practitioners selected from 16 hospitals, was conducted during the period from February to March 2003.

RESULTSOnly 2.7% of the interviewees knew the definition of adverse drug reactions. 61.7% of the doctors, 62.7% of the nurses and 61.1% of the administrators had ever encountered an ADR during their practices, but did not report to the national monitoring center or other centers. The major reasons for not reporting included: ignorant about the requirement and the reporting process of ADR (71.4%); address of the reporting agency and Forms unavailable (67.9%, 60.4%); unaware of the existence of a national ADR reporting system (52.2%); needless to report as the ADR being too well known (44.1%). They mainly reported an ADR to the hospital pharmacy or other departments, or to the pharmaceutical administration. Education, training and developing new institutions were ways to improve the reporting system.

CONCLUSIONSOur results showed that healthcare professionals had little knowledge on the basic ADR knowledge. The main reasons for underreporting were related to factors on reporting process, address of related centers and unavailable of the Forms. Education and training to doctors and nurses to enhance the awareness of administrators were the ways to improve the reporting system.

Adverse Drug Reaction Reporting Systems ; Attitude of Health Personnel ; China ; Drug-Related Side Effects and Adverse Reactions ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Practice Patterns, Physicians' ; Surveys and Questionnaires

Objective:To analyse the clinical presentation and pathogenic gene mutations of a family diagnosed with primary familial brain calcification (PFBC).Methods:A pedigree with primary familial brain calcification was recruited. The clinical data of the proband who was admitted to the Affiliated Hospital of Guizhou Medical University in March 2020 and the family members were collected. The DNA sequence of myogenesis regulating glycosidase (MYORG) gene was detected by Sanger sequencing in the proband and some available family members.Results:The proband is a male, 30 years old. There was only one patient of PFBC in this family. The first symptom of the proband was vagueness of speech, and gradually extrapyramidal symptoms such as slow and flexible movement and advanced cognitive impairment appeared. The brain CT of the proband and his second brother showed extensive symmetrical calcifications, mainly located in the bilateral cerebellar hemispheres, basal ganglia and thalamus. A homozygous mutation in the exon 2 of the MYORG gene [c.1967T>C(p.I656T)] was identified in the proband and an asymptomatic patient. The heterozygous mutation of MYORG gene was also detected in four healthy family members.Conclusions:All patients with homozygous mutations of MYORG gene showed calcification in CT scan, and most of the lesions were located in basal ganglia, cerebellum, subcortical white matter and thalamus. Compared with the patients with autosomal dominant gene mutation, the patients with MYORG gene mutation had more extensive intracranial calcification lesions, and the pontocerebellar lesions were more common. The most common symptoms of MYORG gene mutation patients were dyskinesia, mainly tremor paralysis and unclear speech.

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell's endogenous protein degrada-tion machinery.However,the susceptibility of proteins for targeting by TPD approaches,termed"degradability",is largely unknown.Here,we developed a machine learning model,model-free anal-ysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein tar-gets.MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision-recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to inde-pendent non-kinase proteins.We found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most predictive.By structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase degradability.Finally,we extended MAPD predictions to the entire proteome to find 964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.

OBJECTIVETo compare the clinical effect of Chinese medicine (CM) and Western medicine (WM) for controlling the recurrence of pelvic endometriosis after a conservative operation.

METHODSThe study was a multi-center, randomized, parallel controlled and prospective clinical trial. Patients were randomly divided into two groups: CM group (106 cases) and WM group (102 cases). Drugs were given to patients during 1-5 days of the first menstruation after a conservative operation in both groups. Patients with stages I and II (revised American Fertility Society) were treated for 3 months, while the patients with stages III and IV were treated for 6 months. The patients in the CM group were treated using three types of Chinese herbal medicine based on syndrome differentiation. Patients in the WM group were treated using gonadotropin releasing hormone agonist (GnRH-a) or gestrinone. Patients treated with GnRH-a received add-back therapy of Tibolone Tablets once a day after 4 months of treatment. Any cases of dysmenorrheal chronic pelvic pain, menstruation and any adverse reactions of patients were recorded once a month during the preoperative and postoperative periods and once every 3 months during the follow-up period. During the preoperative, postoperative and the follow-up periods, patients underwent type B ultrasonography of the pelvis and measurements of serum CA125 levels, gynecologic examination, routine evaluations of blood, urine, hepatic function (glutamate pyruvate transaminase), renal function (blood urea nitrogen) and electrocardiograms. During the follow-up period they underwent type B pelvic ultrasonography, measurement of serum CA125 levels and further gynecologic examinations. The two treatments were compared for clinical recurrence rates, pregnancy rates and the incidence of adverse reactions.

RESULTSThe incidence and timing of recurrence of endometriosis were not significantly different between the two groups. The first pregnancy achieved by the patient in the CM group was significantly earlier than that in the WM group (P <0.05). Moreover, the incidence of adverse reactions in the WM group was significantly higher than in the CM group (P <0.01).

CONCLUSIONSTreatment with Chinese herbal medicines prevented the recurrence of endometriosis after a conservative operation, improved the conception rate and showed fewer and lighter adverse reactions than did treatment with WM therapy. Treatment with Chinese herbal medicine meets the need of patients wishing to have a child following endometriosis and is an appropriate form of clinical treatment.

Adult ; Demography ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endometriosis ; drug therapy ; surgery ; Female ; Humans ; Pelvis ; surgery ; Pregnancy ; Recurrence