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 evaluate the mental health of medical workers, and develop an EAP suitable for heahhcare sector. Methods A 1-year EAP was implemented in a hospital in Beijing, in which SF-36 and JSS scales were used to study the health-related quality of life and job satisfaction of these workers. Results Work pressure is found to be the main source of pressure for medical workers, accounting for 63.7%. Scores of the group receiving EAP service are found to be significantly higher (P<0.01) in all dimensions (excepting work nature and supervisor dimension) of both SF-36 and JSS. Conclusions Medical workers are exposed to high pressure of work, having strong need for EAP service as result. EAP is an effective means to maintain mental health and improve quality of life and job performance, if applied widely.

Objective To investigate the expression and distribution of basic fibroblast growth factor (bFGF)and platelet-derived growth factor (PDGF)in the different phases of femoral neck fracture.Methods Immunohistochemical assays were used to determine the expression and distribution of bFGF and PDGF protein in 36 human specimen of femoral neck fracture.A was measured and analyzed by CMIAS color imaging analysis system for signals of bFGF protein were found high in the mesenchymal cells,monocyte and vascular endothelial cells at 1st week after fracture in 9 subjects,with A of (0.4076 ±0.0902).The weakly positive signals of PDGF protein were found in the mesenchymal cells,while strongly positive in the vascular endothelial cells with A of (0.2261 ±0.0636).At 2rd week,in 9 cases the expression of bFGF and PDGF was strongly expressed in fibroblasts,endothelial cells,cartilage cell and cartilage matrix,osteoblast,with A of[(0.6404±0.0920)and (0.7457±0.0756)]and significandy higher than that at 1st week (P＜0.05,P＜0.01).There was no significant difference between the 3rd and 3nd week with A of[(0.7168±0.1346)and (0.8033±0.0491),P＞0.05 ].The expression of bFGF and PDGF protein was reduced obviously at 4th week but was positive in young and cartilage tissue,with A of [(0.5374correlation between bFGF and PDGF protein in different phases (r1week=0.792,r2week=0.834,r3week=0.880,entiation of cartilage cell and osteoblast,and induce proliferation of vascular endothelial cells and new blood vessel.③ Both bFGF and PDGF are bone growth factors, cooperating in regulating proliferation and differentiation of cartilage cell and osteoblast for fracture healing.

AIM: To observe the effects of Salvia miltiorrhiza Bunge.f.alba. (Sal) on the mitochondrial ultra-structure, oxidative stress and apoptosis induced by ischemia injury in a rat model of focal cerebral ischemia and reperfusion.METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established by a modified Longa occlusion method. Adult male SD rats were randomly divided into control group, simple ischemia reperfusion group, Sal with ischemia reperfusion group and butylphthalide with ischemia reperfusion group. To study the protective effects of Sal and its mechanism, the intervention of Sal was given and the ultra-structure of mitochondria, functions of mitochondria under oxidative stress and the incidence of apoptosis of brain cells were determined.RESULTS: Many electron dense toxic granulation and vacuolus in mitochondria were observed in the rat brain of focal cerebral ischemia and reperfusion. Under the condition of ischemia and reperfusion, the mitochondria membrane was disaggregative, and the tubular cristae of mitochondrion disappeared. MDA content was obviously increased and the activity of glutathione peroxidase decreased significantly. The apoptosis of brain cells were observed in a great quantity. The changes of ultra-structure of mitochondria and the activity of GSH-Pxase were significantly improved by the treatment of Sal. Furthermore, treatment with Sal delayed the decrease of GSH-Pxase activity, and inhibited the increase in MDA content in brain tissue after ischemia and reperfusion. The incidence of apoptosis of brain cells was also decreased.CONCLUSION: Sal protects the brain tissue from ischemia injury.