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.

Adenoma, Pleomorphic ; surgery ; Adult ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; surgery

Objective To analyze the clinical features and prognostic factors of lymphoma.Methods The clinical data,pathologic data and survival state of 253 patients with lymphoma in Qinghai were retrospectively studied.The survival differences of patients with different clinical characteristics and laboratory tests were analyzed using Kaplan-Meier method.The prognostic factors of lymphoma were analyzed by Cox proportional hazards regression model.Results Among all of 253 cases of lymphoma,males were in the majority (male∶female =1.56∶1).The median age of patients was 48 years old.There were two peaks of about 40 years old and 60 years old in age of onset.The nodal lymphoma (56.13 ％) was more commonly than the extranodal lymphoma (43.87 ％).The more common extranodal lymphomas were found in the nasopharynx and gastrointestinal tract.Among all cases,40 cases (15.81％) were confirmed to be Hodgkin lymphoma (HL),of which,the commonest subtype was nodular sclerosis (72.5 ％).While 213 of 253 cases (84.19 ％) belonged to non-Hodgkin lymphoma (NHL),of which,B-cell lymphoma was 148 cases (69.48 ％).Overall,three subtypes including diffuse large B-cell lymphoma (39.91％),follicular lymphoma (12.21％) and peripheral T-cell lymphoma (9.39 ％) were the commonest subtypes among all cases.Univariate analysis showed that the clinical stage,B symptoms,Hb concentration,serum LDH level,international prognostic score (IPI) and treatment programs were related to the prognosis of NHL (P ＜ 0.05).However,the Cox regression multivariate analysis showed that only the clinical stage,IPI and treatment programs,not B symptoms,Hb concentration and serum LDH level,were closely related to the prognosis of NHL (P ＜ 0.05).Conclusions In Qinghai area,there are two peaks of about 40 and 60 years old in the age of onset of lymphoma.The nodal lymphoma is more than extranodal lymphoma.B-cell lymphoma is more common.IPI could be as an independent prognostic factor and might be used to estimate the prognosis of NHL.

Objective To study the relationship between the health?related quality of life and Graves′ophthalmopathy quality of life(GO?QOL)in Graves′ophthalmopathy(GO)patients. Methods A total of 44 GO patients were recruited for the study and investigated with SF?36 and GO?QOL questionnaires. In addition,the thyroid function and related antibodies were also detected. Results The scores of SF?36 and GO?QOL were higher in the patients over 45 years than those under 45 years(P<0.05). GO?QOL score was lower in the patients with thyroid stimulating hormone recep?tor antibody higher than 10 IU/mL(P<0.05). The scores of SF?36 and GO?QOL were obviously higher in the patients who had a clinical activity score above 3(P<0.01). Conclusion GO?QOL is a better and more specific questionnaire for GO patients.

Objective To investigate the change of indications of emergency obstetric hysterectomy and the clinical application of intraoperative interventions. And to provide evidence for prevention of hysterectomy and improvement of obstetric quality. Methods Clinical data were collected from 97 patients who received emergency obstetric hysterectomy at Shengjing Hospital of China Medical University between January 1st, 2004 and December 31st, 2013. The patients were divided into two groups by the time point of January 1st, 2009: the first group was cases treated between January 1st, 2004 and December 31st, 2008, while the second group was cases treated between January 1st, 2009 and December 31st, 2013. The clinical indicators, surgical indications, intraoperative interventions, and blood loss between the two groups were analyzed retrospectively. Results (1) Incidence:54 857 women delivered at Shengjing Hospital of China Medical University between January 1st, 2004 and December 31st, 2013. Of them, 97 patients received emergency obstetric hysterectomy, with an incidence of 0.177% (97/54 857). (2) The 17 patients delivered vaginally (18%,17/97) and 80 by caesarean section (83%,80/97). Forty-nine patients experienced repregnancy with scar uterus (51%, 49/97). About 41 patients underwent abdominal total hysterectomy (42%,41/97) and 56 received subtotal hysterectomy (58%,56/97). (3) The number of patients were comparable between the two groups (50 vs 47;P>0.05). (4) The main surgical indication was uterine inertia (45%, 44/97). The main causes of uterine inertia were excessive uterine tension (45%, 20/44) and placental abruption due to gestational hypertension (32%, 14/44). Of all the indications, 29 patients in the first group (58%, 29/50) and 15 patients in the second group (32%, 15/47) suffered from postpartum hemorrhage. Pathological placenta embedment occurred in 15 patients in the first group (30%, 15/50) and 25 patients in the second group (53%, 25/47). The incidences of postpartum hemorrhage due to uterine inertia or pathological placenta embedment were significantly different between the two groups (both P<0.05), respectively. (5) In the first group, the average preoperative blood loss was (2 900±1 900) ml, and the average intraoperative amount of infused white&red blood cells was (5.9±3.5) U, with the average operation time of (2.2 ± 1.8) hours and the average in-hospital duration of (7.8 ± 2.3) days. In the second group, the average preoperative blood loss was (3 100± 2 200) ml, and the intraoperative amount of infused white&red blood cells was (6.2± 5.2) U, with the average operation time of (2.5± 2.1) hours and the average in-hospital duration of (7.9 ± 2.9) days. There was no significant difference between the two groups in any of these indicators (P>0.05). Postpartum hemorrhage was usually treated with uterine packing in the first group, but was preferentially treated with potent uterine contraction agents, arterial ligation, uterine balloon compression or B-Lynch suture in the second group. The therapeutic effects of these new treatments were significantly better than uterine packing (P<0.05). Conclusions The incidence of emergency obstetric hysterectomy did not change significantly in the past decade. However, the indications and intraoperative interventions have changed significantly in the second five years compared with the first five years. The main surgical indications were uterine inertia and postpartum hemorrhage due to pathological placenta embedment. Therefore, strict control of caesarean section indications was important to reduce emergency obstetric hysterectomy.

Objective To investigate the antimicrobial resistance of Haemophilus influenzae in Peking Union Medical College Hospital for rational clinical treatment.Methods A total of 223 strains of H .influenzae were collected from patients from Jan-uary 2008 to December 2011.The antimicrobial susceptibility was tested by Kirby-Bauer method.Production of beta-lactamase was detected using nitrocefin disks.WHONET 5.6 software was used to analyze the data of susceptibility testing.Results Tri-methoprim-sulfamethoxazole and tetracycline were the two antimicrobial agents to which the H .influenzae strains were most resistant.Theβ-lactamase positive ampicillin resistant strains accounted for 15.9 %,andβ-lactamase negative ampicillin resist-ant strains accounted for 8.9%.Conclusions H .influenzae is mainly isolated from respiratory specimens.Majority of the anti-microbial agents still show good antibacterial activity against H .influenzae strains.However,H .influenzae isolates are highly resistant to trimethoprim-sulfamethoxazole and tetracycline.

Objective Though measuring the expression levels of blood aryl hydrocarbon receptor (AhR) and cytochrome P-450 1A1 (CYP1A1),to explore the relationship between the expression levels and chronic arsenic poisoning induced skin changes.Methods Totally 233 residents were selected in Hanggin Rear Banner arsenic exposure area of Bayannur City,according to water arsenic concentrations,these people were divided into control (＜ 10 μg/L,55 people),low (10-＜ 100 μg/L,47),medium (100-＜ 200 μg/L,45) and high (≥200 pg/L,86) arsenic exposure groups.Real-time PCR was used to detect the expression levels of blood AhR and CYP1A1 mRNA,which were presented in median and quartile [M (Q1-Q3)],and the relationships between their expression levels and keratosis,depigmentation of skin were analyzed.Results The relative expression levels of AhR and CYP1A1 mRNA in high-dose groups were 3.18 × 10-3 (2.42 × 10-3-4.45 × 10-3) and 1.58 × 10-3 (0.80 ×10-3-2.73 × 10-3),which were higher than those in control groups [2.30 × 10-3 (1.53 × 10-3-3.20 × 10-3) and 1.00 × 10-3 (0.59 × 10-3-2.09 × 10-3)],and the difference were statistically significant (all P ＜ 0.05).Compared with control group,the detectable rates of arsenic poisoning,keratosis and depigmentation of skin were higher,and the differences were statistically significant (x2 =20.187,15.848,21.595,all P ＜ 0.05).The detectable rates of arsenic poisoning,keratosis and depigmentation of skin were increased with increase of water arsenic concentrations (x2 =19.012,15.269,16.868,all P ＜ 0.05).Compared with normal [2.54 × 10-3 (1.79 × 10-3-3.43 × 10-3),2.57 × 10-3 (1.78 × 10-3-3.52 × 10-3)],AhR mRNA relative expression levels [4.45 × 10-3 (3.47 × 10-3-8.04 × 10-3),4.45 × 10-3 (4.02 × 10-3-6.25 × 10-3)] of degree Ⅲ keratosis and depigmentation of skin were increased,and the differences were statistically significant (all P ＜ 0.05).Conclusions Chronic arsenic exposure affects the expression level of AhR and CYP1A1 mRNA.Blood AhR mRNA expression may have relationship with endemic arsenic poisoning induced skin change,but blood CYP1A1 mRNA expression may have nothing to do with endemic arsenic poisoning induced skin change.

Objective To evaluate the clinical effect of different oral care solution.Methods Literature data were collected by computer retrieval covering China National Knowledge Infrastructure (CNKI),China Biology Medicine (CBI) and Wanfang database,and Note Express and Addis software were used to evaluate the randomized controlled trials of literature.Results 19 separate randomized controlled trials were included in the research hterature;Network Meta analysis results showed that in the prevention of ventilator-associated pneumonia,the electrolyzed oxidizing water,compound chlothexidine,hydrogen peroxide,sodium bicarbonate,distilled water and 0.9％ saline had statistically significant difference (OR=0.25,95％CI=0.02-0.72),and the effect of sodium bicarbonate was better than the other oral care solutions;in the prevention of oral odor,the oral care solution had no significant difference (OR=0.86,95％CI=0.34-1.74),and sodium bicarbonate of the total ranked the best preventive effect;in the prevention of oral infection,the oral care solution had no significant difference (OR=0.62,95％CI=0.09-1.60).Conclusions Based on the meta analysis results,with 0.9％ saline for common interventions,sodium bicarbonate oral nursing liquid is superior to other oral nursing liquid in the prevention of ventilator-associated pneumonia,oral smell and infection.

Objective To observe the location of pelvic organs, the morphology and function of levator ani muscle (LAM) in primiparous women post vaginal delivery at 6 months postpartum using static and dynamic MRI, and investigate the correlation between LAM injury and pelvic organ prolapse (POP). Methods A perspective analysis of static and dynamic MRI was performed in fifty-one primiparous women post vaginal delivery at 6 months postpartum and thirty-five nulliparous women without experience of pregnancy and delivery as control group from June 2014 to January 2015. Previous pregnancy and abortion history, previous pelvic surgery and pelvic mass diseases were excluded. Cases with pelvic floor dysfunction symptoms were excluded from the control group. All of the women underwent static and dynamic MRI. The primiparous group was divided into two groups on presence or absence of POP on MRI findings:primiparous POP group and primiparous control group. The levatorani scoring system based on static MRI was used to characterize morphological changes of LAM into none, minor and major injury by the total score of bilateral LAM. A series of parameters including H line (the distance between the inferior margin of pubic symphysis to anorectal junction), M line (the perpendicular distance between the distal end of H line to pubococcygeal line), levator plate angle (LPA), iliococcygeal angle (ICA), and levator hiatus length and area were measured on static and dynamic MR images. Fisher exact test was performed to compare difference in distribution of the LAM injury between the primiparous group and control group, as well as the primiparous POP group and primiparous control group. Independent sample t test or Mann-Whitney test was used to compare difference in LAM parameters between the primiparous POP group and primiparous control group. Results In the 51 cases primiparous group, 44 cases showed none injury, whilst 5 cases with minor and 2 cases with major injury in the puborectal muscle. Thirty two cases showed none injury, whilst 10 cases with minor and 9 cases with major injury in the iliococcygeal muscle. In the 35 cases control group, none injury was shown in puborectal muscle, whilst 32 cases with none, 2 cases with minor and 1 case with major injury in the iliococcygeal muscle. There was no significant difference in the puborectal muscle injury between the two groups (P=0.203), and there was significant difference in the iliococcygeal muscle injury between the two groups (P<0.05). In the 24 cases primiparous POP group, 20 cases showed none injury, whilst 2 cases with minor and 2 cases with major injury in the puborectal muscle. Fourteen cases showed none injury, whilst 6 cases with minor and 4 cases with major injury in the iliococcygeal muscle. In the 27 cases primiparous control group, 24 cases showed none and 3 cases with minor injury in the puborectal muscle, whilst 18 cases with none, 4 cases with minor and 5 cases with major injury in the iliococcygeal muscle. There was no significant difference in the puborectal muscle injury and iliococcygeal muscle injury between the two groups (P=0.588 and 0.559, respectively). The LH during Valsalva status in primiparous POP group and primiparous control group were (6.7 ± 1.1) and (5.0 ± 0.6) cm, respectively, whilst the LHA was (41.6 ± 12.6) and (24.2 ± 5.5) cm2. There were significant difference between the corresponding groups (P=0.042 and 0.004, respectively). There was no significant difference between the corresponding groups of the other LAM parameters on static and dynamic MRI (all P>0.05). Conclusion Vaginal delivery may cause various degrees of LAM injury, the LAM functional deficiency were observed in primiparous women combined with POP.

Adrenomedulin is an angiogenesis peptide that was found recently.It plays a critical role as an autocrine/paracrine tumor cell survival factor.Recently,adrenomedulin has been proved that it is overex- pressed in tumor,such as breast cancer.It may have a significant role in tumor progression and differentiation by stimulating mitogenic activities,inhibiting immune response,inhibiting apoptosis and enhancing angiogen- esis.We may realize targeted therapy tumor by intervening adrenomedulin,its receptor,and the signal con- duction pathway.