With the development of antibody manufacturing technology and improvement of new drug research in domestic industry, more innovative monoclonal antibody products submitted investigational new drug (IND) application. At the same time, monoclonal antibody products from abroad which have been approved marketing authorization and/or conducted clinical trials submitted IND applications in China. The National Medical Products Administration (NMPA) issued the "Guideline of Investigational New Drug Application" (No. 16, 2018) which emphasized the chemical, manufacturing, and control (CMC) regulatory, and dossier requirements in IND application, greatly promoted the application quality of innovative biological products. However, compared to the Food and Drug Administration (FDA) and European Medicines Agency (EMA), our particular guidelines are insufficient, such as guideline on virus safety evaluation of biotechnological investigational medicinal products. This review investigated the questions raised by sponsors from 2018 to 2020, including the end of production cell (EOPC) and/or unprocessed bulk (UPB) testing and virus removal or inactivation validation. Meanwhile, sponsors submitted different dossiers due to differences in understanding of stage requirements of guidelines from domestic and abroad. Based on the guidelines of virus safety from NMPA, FDA, and EMA, and the technical considerations, this review puts forward personal suggestions on the adventitious agents testing and virus removal or inactivation validation in manufacturing process, aim to ensure virus safety of innovative monoclonal antibody products in clinical trials.

Objective:Putting digital electrocardiograph detection method into practice, some problems could be find out and analyzed. Moreover, the quality safety of digital electrocardiograph can be guaranteed.Methods: According to the relevant national standards and regulations, EGC-1 c type verification instrument and CMRR tester can be used to detect the electrocardiograph. By checking the appearance of the electrocardiograph machine, testing various performance parameters to judge the accuracy of the electrocardiograph machine.Results: Through regular detection, not only can eliminate potential risk of digital electrocardiograph but also can make sure quality safety of clinical use.Conclusion: Quality control detection to digital electrocardiograph is an important component of medical safety. Detection on time and maintenance in time can ensure that the measurement size of monitors is correct and credible and these monitors serve the patients better.

Female ; Hamartoma ; Humans ; Infant, Newborn ; Mouth Diseases ; Palate, Soft

Objective The incidence of laryngeal cancer has characteristic of regional differences, but the etiology is not clear. The aim of this study was to analyze the correlation between RECK gene promoter methylation and prognosis of laryngeal squamous cell carci-noma patients through detecting the RECK gene methylation status of primary laryngeal squamous cell carcinoma and adjacent tissues . Methods Methylation specific PCR assay was used to detect the RECK gene promoter methylation status of 70 laryngeal squamous cell carci-noma specimens in our hospital from July 2006 to Dcember 2007, and the differences of methylation status with different pathological parame-ters were compared.The correlation between RECK gene promoter methylation and prognosis of 64 patients completed five-year follow-up was analyzed. Results The RECK gene methylation rate (86.67%) of patients with poor differentiation in tumor cells was much higher than that of the patients with a moderate and better tumor cell differentiation (43.64%) (P<0.05).In 29 pairs of laryngeal cancer-adjacent tis-sues specimens matches, the RECK gene methylation in laryngeal carcinoma (55.12%) was higher than normal tissues (27.59%) ( P=0.029).RECK gene methylation significantly shortened the tumor free survival and overall survival analyzed by Log-rank (P=0.024, P=0.017).Lymph node metastasis and clinical stage in classⅢ-Ⅳsignificantly shortened the tumor free survival and overall survival (P=0.029, P=0.024;P=0.033, P=0.032).Moderate and better tumor cell differentiation significantly shortened the tumor free survival (P=0.024, P=0.049).Lymph node metastasis, clinical stage, and RECK gene methylation were independent risk factors of overall survival. Conclusion RECK gene promoter methylation in human laryngeal squamous cell carcinoma is an early event and may occur in the adjacent normal tissues, predicting a poor prognosis in patients.

Objective:This study has two objectives. One is to detect the methylation status of reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a new tumor suppressor gene) gene promoter in primary laryngeal squamous cell carcinoma and nor-mal laryngeal mucosa. The other is to analyze the correlation between RECK gene methylation status and radiosensitivity in laryngeal squamous cell carcinoma. Methods:Methylation-specific polymerase chain reaction was used to detect the RECK gene methylation of 70 specimens of laryngeal squamous cell carcinoma and 15 normal tissues of laryngeal mucosa. The patients underwent six cycles of ra-diotherapy and were followed-up for 5 years. The correlation between RECK gene methylation status and radiosensitivity in laryngeal squamous cell carcinoma was analyzed. Results: After six cycles of radiotherapy, 47 patients (67.14%) showed sensitivity and 23 (32.86%) showed tolerance to radiotherapy. The methylation level of the RECK gene was lower in the radiation-sensitive group than in the nonradiation-sensitive group (P<0.05). The methylation level of the RECK gene was lower in the remission group than in the non-remission group. RECK gene methylation could increase the risk of cancer by approximately 5.010 times (OR=5.010, 95%CI:1.616-15.533). Conclusion:RECK gene promoter methylation in human laryngeal squamous cell carcinoma is an early event that is correlated with the patient's sensitivity to radiotherapy. Thus, the patient's sensitivity to radiation can be predicted by detecting the meth-ylation status of the RECK gene promoter.

OBJECTIVE: To investigate the protective effect of celastrol on allergic rhinitis rats and its possible mechanism. METHOD: Allergic rhinitis (AR) model of rats was established by OVA. The behavioural characteris tics were observed at the 1st, 4th and 7th dayafter stimulation treatment. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-PX) in the nasal mucosa breathing zone were measured. The expression of the nuclear factor erythroid 2 related factor 2 (NRF2) nuclear protein and the catalytic submit of glutamylcysteine ligase (GCLC) cytoplasmic protein in the nasal mucosa breath ing zone were determined. RESULT: We observed obvious behaviour changes related with allergic rhinitis in AR rats, together with decrease of SOD, GSH and GSH-PX and increase of MDA in the nasal mucosa breathing zone. Moreover, NRF2 nuclear protein expression and GCLC cytoplasmic expression were suppressed in the nasal mucosa. The changes above were alleviated in celastrol pretreatment group. The potential mechanism may be related to the upregulation of NRF2 nuclear protein expression and GCLC cytoplasmic expression after celastrol pretreatment. CONCLUSION Celastrol can significantly relieve the allergic symptoms in AR rats. The mechanism of this protective effects may relate to the upregulation of NRF2 nuclear protein expression and GCLC cytoplasmic expression in the nasal mucosa breathing zone.
Animals ; Disease Models, Animal ; Glutamate-Cysteine Ligase ; metabolism ; Male ; NF-E2-Related Factor 2 ; metabolism ; Nasal Mucosa ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic ; drug therapy ; Triterpenes ; therapeutic use

Objective To evaluate the value of volumetric brain MRI in multiple system atrophy.Methods Eleven patients diagnosed as multiple system atrophy were recruited,includin 5 parkinsonism dominant(MSA-P)and 6 cerebellar dominant(MSA-C).9 patients with parkinsonism of other types and 6 healthy persons were set as case control and healthy control,respectively.T1 weighted (T1W)sagittal and axial images and T2-weighted(T2W)axial images were obtained from all patients and controls at 3.0T scanner.Diameters of the brain structures were measured infratentorially(brainstem, middle cerebellar peduncles(MCP),dentate and red neelus)and supratentorially(globns pallidus and putamen).Results The transverse diameter of the pons was significantly smaller in MSA patients than in the case and healthy controls((27.6?2.0)mm and(30.5?0.6)mm and(29.9?1.1)mm).The significance could be seen when comparing MSA-C and MSA-P with healthy control.The anteroposterior diameter of the fourth ventricle was significantly dilated in MSA patients than in healthy control((11.9? 2.8)mm and(9.0?2.1)mm).The MRI of MSA-C showed narrower MCP((13.3?1.9)mm and (15.8?1.2)mm and larger fourth ventricle((17.3?2.1)mm and(12.6?2.7)mm)than that of MSA-P.The MRI of MSA-P showed smaller globus pallidus and red neclei.Conclusions The volumetric MRI is a useful means in evaluating the brain structure atrophy in multiple system atrophy.The transverse diameter of the pans,though objectively reflecting the atrophy of the pons,can' t be used to differentiate MSA-P from MSA-C.The atrophy of MCP and the dilated fourth ventricle are common in MSA-C,while the atrophy of red neclei is common in MSA-P.

Objective To investigate the mycoplasma pneumoniae(MP) infection of the respiratory tract infection in children,the macrolide-resistant situation and resistance mechanism of MP. Methods The cultured throat swab specimens were obtained from 80 pediatric outpatients with respiratory tract infection from Dec.2008 to Mar.2009 in Beijing friendship hospital.The 23S rRNA gene of throat swab specimens and positive-cultured specimens were amplified using nested-PCR,and the products were further verified by electrophoresis and DNA sepuencing,which were collected from the outpatients.The specimens were divided into 2 groups depending on the findings of the gene sequencing whether they had gene mutation:sensitive and resistance group.The DNA sequence of samples were compared to the sequence of MP reference strain in genbank in order to findout MP drug resistant gene.The differences in macrolids therapy were investigated between 2 groups before the throat swab obtained.The drug resistance rates were compared between outpatients and inpatients. Results Thirty-two throat swab specimens were proved to be MP by direct nested-PCR,and 8 throat speeimens were proved to be MP by isolation and culrures.Total 33 cases(including 1 was positive-culture but nagative-direct PCR) were proved to be MP positive.Sixteen were identical to the M129 standard sequence,and 17 had point mutation in gene of 23S rRNA V region.Ten had A to G mutation at position 2063,3 had A to G mutation at position 2064,2 had A to G mutation at position 2067,1 had G to A mutation at position 2062,1 had A to T mutation at position 2063.There was no significant difference between the sensitive and resistance group in whether had macrolids before the throat swab obtained(P =0.909).And there was no significant difference in MP drug resistance rate between outpatients and inpatients(P =0.459). Conclusions The major mutation were A2063G and A2064G,and A2063T,A2067G,G2062A were newly found mutation points which were possibly related to macrolids resistance.

Atrophy ; Brain ; pathology ; Child ; Female ; Humans ; Muscle Fibers, Slow-Twitch ; pathology ; Neuromuscular Diseases ; congenital ; pathology

ObjectiveTo evaluate the efficacy of preoperative oral pregabalin for attenuating postoperative pain after laparoscopic cholecystectomy.MethodsIn this prospective,randomized controlled double-blind study,sixty ASA Ⅰ or Ⅱ patients aged 19-72 yr weighing 46-86 kg undergoing laparoscopic cholecystectomy were randomly divided into 2 groups ( n =30 each):control group (group C) received placebo,and pregabalin group (group P) received oral pregabalin 150 mg 1 h before surgery.Anesthesia was induced with propofol,fentanyl and rocuronium and maintained with sevoflurane inhalation and intermittent iv boluses of fentanyl and rocuronium.The patients were intubated and mechanically ventilated.BIS value was maintained at 40-50 during operation.Static and dynamic VAS score,Ramsay score and consumption of morphine were recorded at 6,12,and 24 h after surgery.Side-effects including nausea,vomiting,headache and dizziness were also recorded.ResultsStatic and dynamic VAS scores and morphine consumption were significantly lower during the first 24 h after surgery while Ramsay scores were higher at 6 h after operation in group P than in group C.There was no significant difference in the incidence of side-effects between the 2 groups.No over-sedation occurred in group P.ConclusionPreoperative oral pregabalin 150 mg is safe and effective in reducing postoperative pain after laparoscopic cholecystectomy.