Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs.
Antibodies, Monoclonal ; chemistry ; Antibody Specificity ; Binding Sites, Antibody ; Immunoconjugates ; chemistry

Objective To study the urodynamic characteristics of women with pelvic organ prolapse in prolapse and reset condition. Methods From Jan. 2010 to Apr. 2010, 30 patients with pelvic organ prolapse (POP), including 1 case in grade Ⅰ , 6 cases in grade Ⅱ , 21 cases in grade Ⅲ and 2 cases in grade Ⅳ, treated in Peking University People's Hospital were analyzed their urodynamical changes at status of prolapse and reset with pessary. Results (1)The symptoms: in the prolapse condition, there were 11 patients with bladder outlet obstruction( BOO), 7 patients with residual volume more than 100 ml, and 4 patients with stress urinary incontinence(SUI). In the reset condition, there were 5 patients with BOO,5 patients with residual volume more than 100 ml, and 4 SUI patients. (2) Characteristics of urodynamic:there were significant difference in first desire to void ( FD, P = 0. 047), normal desire to void ( ND, P =0. 007), strong desire to void ( SD, P = 0. 001 ), maximum cystometric capacity ( MCC, P = 0. 001 ),maximum flow rate ( Q=max, P = 0. 001 ), average flow rate ( Q P = 0. 001 ), and residual volume ( RV,P = 0. 025 ) between prolapse and reset condition among all patients. In patients with grade Ⅰ to Ⅱprolapse, Qmax were (11 ±6) ml/s in prolapse condition and (15 ±4) ml/s in reset condition (P =0. 014), Qave were ( 6 ± 4 ) ml/s in prolapse condition and ( 7 ± 3 ) ml/s in reset condition ( P = 0. 237 ),RV were (29 ±46) ml in prolapse condition and (15 ±25) ml in reset condition (P =0. 157). Among patients with grade Ⅲ to Ⅳ prolapse, Qmax were ( 11 ± 8 ) ml/s in prolapse condition and ( 17 ± 10) ml/s in reset condition (P=0.001), Qave were (5 ±4) ml/s in prolapse condition and (7 ±4) ml/s in reset condition ( P = 0. 002 ), RV were ( 105 ± 169 ) ml in prolapse condition and (47 ± 92) ml in reset condition (P = 0. 037 ). Conclusions Patients with pelvic organ prolapse Ⅲ - Ⅳ may present pseudo BOO,recessive stress urinary incontinence and residual volume more than 100 ml. There were significant improvement in cystometric sensation, capacity, flow rate, and residual volume after reset. The urodynamic test for patients with pelvic organ prolapse in the reset condition might be much better in evaluating lower urinary tract function.

BACKGROUND:Since the meniscal blood supply is only in the red zone, the synovial fluid becomes the main nutrition source of the meniscus. As its poor self-healing ability, the meniscus is almost impossible to heal in non-blood supply regions. OBJECTIVE:To investigate the expression and characteristics of transforming growth factor-β3 in the rat meniscus during postnatal development. METHODS:Meniscus tissues of Wistar rats with different ages (1, 7, 14, 21, 28, 35 days) were adopted, and immunohistochemistry and RT-PCR methods were performed to detect the location and expression pattern of transforming growth factor-β3 within the meniscus. RESULTS AND CONCLUSION: Immunohistochemistry results revealed that the expression of transforming growth factor-β3 started from the joint capsule, and gradualy extended to the red zone, gray zone, and white area;RT-PCR results showed the mRNA expression of transforming growth factor-β3 in the rat meniscus at different ages, and during development process gradualy increased until adult stage (rat weight > 100 g), which remained relatively stable.

One-and-a-half syndrome with facial diplegia, also referred to as the fifteen-and-a-half syndrome, is an extremely rare clinical entity caused by involvement of bilateral tegmentum of pons. Herein, we report a 52-year-old male who presented with one-and-a-half syndrome with left facial paralysis, which was consistent with the so-called eight-and-a-half syndrome. Brain magnetic resonance imaging showed pontine infarction. Five days after initiation of antiplatelet therapy, the patient developed right facial paralysis, a diagnosis of fifteen-and-a-half syndrome was made, repeat MR imaging revealed bilateral pontine tegmentum infarction. Fifteen-and-a-half syndrome is a newly proposed concept associated with pontine infarction. The clinicoradiological features of this specific disease are as yet unclear due to its extreme rarity. The current case would help advance the current understanding of the disease spectrum of pontine infarction.

ObjectiveTo investigate the localization G protein couple receptor 30 (GPR30) and its mRNA in submaxillary gland, and to supply theoretic evidence for further studying functional significance of the GPR30 in submaxillary gland of rats. Methods Four male SD rats were sacrificed by cervical dislocation after the intraperitoneal anesthesia, and excised the submaxillary glands. The distribution of GPR30 and its mRNA were studied through immunohistochemistry and in situ hybridization in the experiment. After isolation of the total RNA from the submaxillary gland, RT-PCR was conducted to obtain GPR30 cDNA by using the specific primers. The products of PCR were analyzed by sequencing with Sanger's method. Results The serous acinus epithelial cells and granular convoluted epithelial cells in submaxillary gland of rats showed GPR30 immunoreactivity, which were located in cytoplasm with negative nuclei. GPR30 mRNA hybridized signals were also detected in cytoplasm in the above cells. The products of PCR is identical to that of the GPR30 sequence of rats. Conclusion The serous acinus and granular convoluted epithelial cells not only express GPR30 but also may be a target organ by rapid estrogen signaling pathway in submaxillary gland of rats. This may be involved in the functional regulation of submaxillary gland.

Objective To explore the value of MRI dynamic contrast-enhanced in differentiating adrenal adenomas from nonadenomas with washout rate of enhancement and the increased SI ratio. Methods Thirty-six patients with 41 adrenal masses enrolled into this study. All these masses underwent conventional T 1WI and T 2WI sequence first, and then FMPSPGR sequence through the center of each mass. Precontrast and dynamic contrast-enhanced FMPSPGR scans were preformed after administration of contrast material of Gd-DTPA intravenously. The signal intensity(SI) of masses was measured on the screen by electronic cursor. The washout rate of enhancement and increased SI ratio were compared between adenomas and nonadenomas. The differentiating adrenal adenomas from nonadenomas were carried out based on combination of the washout rate and the increased SI ratio, meanwhile, the sensitivity and specificity of the diagnosis of adenomas were evaluated well.Results The sensitivity and specificity of the diagnosis of adenomas were 74% and 73%,and accuracy was 73% when the washout ratio was used as a indicator at 5 min. The sensitivity and specificity of the diagnosis of adenomas would be improved markedly when the combination of the washout ratio and the increased SI ratio was used as a indicator.The sensitivity and specificity of the diagnosis of adenomas were 95%, 91% respectively,and accuracy was 93%. Conclusion Using MRI dynamic contrast-enhanced based on combination of washout rate of enhancement and the increased SI ratio,the diagnosis and differentiating diagnosis of adrenal adenoma and nonadenoma can be improved.

Objective To investigate the diagnosis and treatment of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.Methods The clinical data of patients with pathologically verified IPMN who underwent surgical treatment between January 2006 to April 2014 in the First Affiliated Hospital of Harbin Medical University were studied retrospectively.There were 27 males and 21 females.The average age was (57.8 ± 8.8) years old.The average caliber of the main pancreatic duct was (1.1 ± 0.6) cm.The average size of the branch duct IPMN was (4.6 ± 1.5) cm.Results 35 patients underwent pancreaticoduodenectomy.Eight patients underwent distal pancreatectomy.Two patients underwent duodenum-preserving pancreatic head resection.Two patients underwent splenic-preserving distal pancreatectomy and one patient underwent total pancreatectomy.No patient died in perioperative period,and the median length of hospital stay after surgery was 14.3 days.Postoperative pathological examination revealed 5 (10.4％) adenoma,12 (25.0％) moderate-grade dysplasia,14 (29.2％) high-grade dysplasia and 17 (35.4％) invasive carcinoma.The postoperative complication rate was 22.9％.The mean follow up period for the noninvasive tumors was 48.9 months,with no recurrence or deaths.The mean follow up period of the invasive tumors was 43.2 months,with 1 death and no recurrence.Conclusions The indications for resection of IPMN should be based on treatment guidelines and on the patient' s general condition.It is suggested that the diagnosis and treatment of IPMN should be conducted in specialized pancreatic surgery centers.

Objective To study the expression of HPV、p16 and Her-2 in the squamous cell cervical carcinoma and its chnical significance. Methods Expression of HPV16/18、p16, and C-erbB-2 and the amplification of Her-2 gene were examined using situ hybridization technique,SP immunohistochemistry,and FISH imaging analysis system in 60 cases of cervical cancer, 61 cases of CIN, and 21 cases of normal cervical tissue,respectively.Results The positive rates of HPV16/18 and p16 in the normal tissue,CIN Ⅰ -Ⅱ,CINⅢ and the squamous cell cervical carcinoma were gradually increased, they wereo (0/21),9.68 ％ (3/31),46.67 ％ (14/30),71.67 ％ (43/60);0 (0/21),19.35 ％ (6/31),93.33 ％ (28/30),96.67 ％ (58/60),respectively,and there were significant differences among the groups (P＜0.05),but no significant difference was found between the normal tissue and the CIN Ⅰ - Ⅱ. The positive rates of Her-2 and Her-2 in the CIN Ⅲ and the carcinoma were 13.33 ％ (4/30),31.67 ％ (19/60),3.33 ％ (1/30),21.67 ％ (13/60),respectively,but in the normal group and the CIN Ⅰ - Ⅱ wereo,and the differences between the carcinoma group and the CIN group,the carcinoma group and the normal group were significant(P＜0.05).The expression of Her-2 and the amplification of Her-2 were closely related to the stage, degree of differentiation and metastasis of lymph node in the squamous cell cervical carcinoma (P＜0.05). Conclusion The infection of HPV is one of thetriggers for the squamous cell cervical carcinoma.The expression of p16 and the amplification of Her-2 may be closely correlated with tumor development and high expression of p16 and Her-2 indicates poor prognosis.

Objective To discuss the effect of daidzein on hepatocellular carcinoma SMMC7721 cell proliferation CD133 expression on tumor stem cell.Methods Hepatocellular carcinoma SMMC7721 cells were cultured,digested and passaged,and divided into six groups with different drug:control group with no daidzein,100 μg/mL daidzein group,200μg/mL daidzein group,300μg/mL daidzein group,400μg/mL daidzein group ,500μg/mL daidzein.The inhibition ratio,hexokinase,alkaline phosphatase and CD133 levels in SMMC7721 cell were detected and compared at 24 h,48 h,72 h among those groups. Results The inhibition ratio was increased by Daidzein dose increasing,and decreased apparently by times extending,especially in 400μg/mL and 500μg/mL daidzeingroups.Compared with control group,the hexokinase and alkaline phosphatase activity and CD133 expression were decreased apparently in groups treated with daidzein(P<0.01).The more the dose,the higher the drop(P<0.01).Conclusion Daidzein can inhibit hepatocellular carcinoma SMMC7721 cell proliferation,and inhibit CD133 expression on tumor stem cell.

Objective To explore the clinical significance of early invasive mechanical ventilation for acute respiratory distress syndrome (ARDS) caused by thoracic trauma.Methods We retrospectively analyzed the clinical data of 93 patients of invasive mechanical ventilation in those with ARDS caused by thoracic trauma,and divided them into delayed invasive mechanical ventilation group (n =45) and timely invasive ventilation group (n =48) by the time of invasive mechanical ventilation.We compared the blood gas analysis,oxygen index,heart rate,lactic acid,muscle use score of the two groups before and after invasive mechanical ventilation and the differences of mechanical ventilation time,incidence of complications,mortality and length of hospital stay between the two groups.Results Each index of the delayed invasive mechanical ventilation group and the timely invasive ventilation group was calculated:PaO2 (63.2 ± 12.3,74.2 ± 12.1)mm Hg,PaCO2 (39.4 ±8.7,38.9 +7.6) mm Hg,PaO2/FiO2 (196.2 ± 17.8,231.4 ± 18.2),respiratory rate (27.4 ±3.7,21.1 ± 3.4) beats/min,heart rate (117.2 ± 26.8,96.0 ± 25.1) beats/min,accessory muscle use score (2.69 ± 0.15,1.67 ± 0.10),lactic acid (4.23 ± 1.70,2.12 ± 0.80) mmol/L Except for PaCO2,the differences of each index were statistically significant (t values were respectively 4.346,9.420,3.949,5.436,38.809,7.736; P ＜ 0.05).The duration of mechanical ventilation treatment (10.21 ± 1.50,6.47 ± 1.20) d and the length of hospital stay (21.53 ± 1.90,16.32 ±2.10) d of the delayed group and the timely group were significantly different (t values were respectively 12.518,13.318; P ＜ 0.01).The timely group had significantly lower mortality rate (26.7％ (12/45),14.6％ (7/48)),VAP (46.7％ (21/45),22.9％(11/48)),acute gastric mucosal lesions (33.3％ (15/45),12.5％ (6/48)),MODS (40.0％ (18/45),16.7％ (8/48)) than the delayed group (x2 values were respectively 3.86,5.81,4.49,5.70; P ＜ 0.05).There is no significant difference on the incidence of pneumothorax between the two groups (11.1％ (5/45),8.3％ (4/48)).Conclusion Invasive mechanical ventilation is an effective treatment of ARDS caused by chest trauma.Early invasive mechanical ventilation can reduce the mortality rate and shorten the duration of mechanical ventilation and hospital stay of the patients with ARDS after severe thoracic trauma.