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

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.

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.

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 analyze reasons for unplanned return-to-theater obstetrical surgery in patients with placenta previa, and to propose a strategy for prevention.Methods Among 571 patients with placenta previa in the Department of Obstetrics, First Affiliated Hospital of Nanjing Medical University from January 2010 to January 2015, ten cases (1.75％) who had an unplanned return-to-theater obstetrical surgery were retrospectively analyzed.Results Seven out of the ten cases returned to the theater due to severe hemorrhage after cesarean section and hysterectomy or uterine artery embolization was performed.The rest three pregnancies were terminated at mid-term with amniotic injection of rivanol, two of which developed severe infection after the induction combined with uterine artery embolization followed by cesarean section,and the other one finally had an emergent hysterectomy due to severe postpartum hemorrhage after cesarean section because of intrapartum hemorrhage.Severe postpartum hemorrhage occurred in eight out of the ten cases, with a mean volume of (4 212± 1 651) ml.Blood loss between the original and return-to-theater surgery was (2 206± 736) ml.In these eight cases, the mean volume of erythrocyte suspension transfusion was (23.7±9.0) U, and [M(min-max)] 1 845(390 3 960) ml for plasma transfusion.Platelet transfusion was performed in five cases, cryoprecipitate transfusion in eight cases, serum albumin transfusion in six cases, and fibrinogen transfusion in five cases.The interval between original and return-to-theater surgery was 2.0(0.5-19.0) h.After the return-to theater surgery, the time of antibiotic use was (9.2±2.3) d, and the duration of hospital stays was (10.6±2.5) d.No patient required further re-operation, and all were discharged without long-term sequelae.All seven neonates had a good prognosis.Conclusions Severe postpartum hemorrhage in patients after initial operation because of placenta previa is the primary indication for unplanned return-totheater surgery.Closed postoperative monitoring, early recognition and expedite return-to-theater surgery are crucial to stop bleeding and save lifes.

Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis which is closely related with abnormal autoimmune.To some extent,it is too difficult to identify the diagnosis between AIP and pancreatic cancer.The treatment includes hormone therapy and surgery.In this article,based on accumulating the experience in the diagnosis and treatment of AIP cases for many years and reviewing the related literatures,we evaluate its type,the etiology and the clinical presentations,as well as summarize the typical characteristics of pathology,radiology and serology.

BacKground:The mechanism of diabetic gastrointestinaI dysmotiIity is stiII uncIear. More and more studies showed that gastrointestinaI smooth muscIe derived factors pIay an important roIe in gastrointestinaI dysmotiIity. RecentIy,the roIe of RhoA/ROCK signaIing pathway in diabetic compIications become a research hotspot. Aims:To investigate the possibIe roIe of RhoA/ROCK signaIing pathway in diabetic coIon dysmotiIity by examining the expressions of major signaIing moIecuIes in diabetic coIon muscIe. Methods:NormaI coIon tissue sampIes taken from patients undergoing radicaI surgery for coIonic cancer from Sept. 2012 to Dec. 2013 at the First AffiIiated HospitaI of Nanjing MedicaI University were coIIected. According to gIycated hemogIobin IeveI,the patients were divided into diabetes meIIitus( DM)group and controI group. The expressions of major signaIing moIecuIes in RhoA/ROCK1 signaIing pathway incIuding RhoA,ROCK1,MYPT1 and p-MYPT1 were determined by immunohistochemistry or Western bIotting. Results:Immunohistochemistry showed that expression of RhoA protein in DM group was significantIy Iower than that in controI group(P<0. 05). Western bIotting showed that expression IeveIs of RhoA,ROCK1 and p-MYPT1 proteins were significantIy Iower in DM group than in controI group(0. 62 ± 0. 42 vs. 1. 15 ± 0. 69,0. 54 ± 0. 09 vs. 0. 75 ± 0. 05,0. 70 ± 0. 28 vs. 1. 04 ± 0. 47;P<0. 05),whereas no significant difference in expression IeveI of MYPT1 protein was found between DM group and controI group(0. 94 ± 0. 50 vs. 1. 21 ± 0. 80,P>0. 05). Conclusions:The inhibition of RhoA/ROCK signaIing pathway in diabetic coIon muscIe may have some correIation with diabetic coIon dysmotiIity.