Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.

Objective To evaluate magnetic resonance imaging (MRI) in the diagnosis of deep anorectal abscess. Methods Twenty-one patients who were suspected of having deep anorectal abscess were admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2006 to December 2007, and their clinical data were retrospectively analyzed. Phased-array coil MRI was applied to all patients before the operation. We compared the efficacy of MRI and rectal digital examination in the classification of deep anorectal abscess and the diagnosis rate of internal opening according to the postoperative results. All data were analyzed using the chi-square test. Results Nineteen patients were diagnosed with deep anorectal abscess, one patient had presacral cyst combined with infection and one patient had perianal mucinous adenocarcinoma. A total of 25 lesions were identified, including 14 ischiorectal abscesses, five pelvirectal abscesses, and six high intersphincteric abscesses. Thirteen patients had single space abscesses and six had multiple space abscesses. There were no significant differences in the diagnosis rate between MRI (12/19) and rectal digital examination for internal opening (13/19) (χ2 =0. 116, P>0.05). The accuracy rate was significantly different between MRI (25/25) and rectal digital examination (16/25) in the classification of deep anorectal abscess (χ2 = 10.970, P <0.05). Operative exploration revealed that there were 13 patients with single space abscesses and six with multiple space abscesses. The accuracy rate was significantly different between MRI (19/19) and the rectal digital examination (13/19) for detecting multiple space abscesses (χ2 =7. 125, P <0. 05). Conclusions MRI with a phased-array coil can accurately detect the extent of deep anorectal abscess and its relationship with anorectal sphincters. MRI examination is helpful in excluding potential lesions in the anorectal region.

ObjectiveTo investigate the correlation between the expression of VEGF and the lymph node metastasis of colorectal carcinoma.MethodsVEGF was detected by immunohistochemistry in 24 cases of colorectal carcinoma with lymph node metastasis and 16 case of colorectal carcinoma without lymph node metastasis.CD34 was used as a marker to evaluate the MVD.All the data were analyzed using 10.1 statistical package.The comparison was performed by x2 test and Spearman rank correlation analysis.The level of significance is α =0.05.Resultsin the 40 cases of colorectal carcinoma,24 cases encountered lymph node metastasis with an MVD (40.65 ± 11.80) and 21 cases were VEGF positive (87.5％).In the 16 cases without metastasis,the MVD was (25.02 ± 11.52) and 4 cases were VEGF positive (25.0％).MVD and VEGF were significantly different between thecases with lymph node metastasis and those without (t =-4.138,x2 =16.00,P ＜0.01 ).In the 40 cases,there were 25 cases with positive VEGF with an MVD (41.33 ± 11.61 ) and 15 cases with negative VEGF with and MVD (22.84 ±8.88).The difference between the cases with positive VEGF and those with negative VEGF (t =5.301,P ＜0.05 ).VEGF level was positive correlated with MVD in the colon cancer ( rs =0.539,P ＜ 0.05 ).Conclusion VEGF may play a role in promoting the lymph node metastasis of colorectal carcinoma

Objective:To study the efficacy of drugs combined with rehabilitation training in the treatment of schizophrenia and the influence on social function. Methods:Totally 160 cases of schizophrene were divided into the control group and the observation group according to the admission time sequence with 80 ones in each. The control group was treated with medicines, and the observation group was given labor skills training, life skills training and health education additionally. The treatment course was 8 weeks. Before and after the treatment, brief psychiatric rating scale ( BPRS) and inpatient rehabilitation efficacy rating scale ( IPROS) were used to evaluate the clinical efficacy and social function of the two groups, and the score changes and curative effect in the two groups were compared. Results:After the treatment, BPRS and IPROS in the two groups were significantly decreased from the fourth week ( P<0. 05), and the reduction degree in the observation group was significantly larger than that in the control group (P<0. 05). There was no statistically significant difference in BPRS and IPROS of efficacy between the two groups (P>0. 05), while BPRS and IPROS of ef-fective rate in the observation group were significantly higher than those in the control group(P<0. 05). Conclusion:Drugs combined with rehabilitation training in the treatment of schizophrenia patients can improve mental symptoms, social life ability and cognitive function, which is better than drug treatment alone.

Objective To investigate the expressions of Transforming Growth Factorβ2 (TGF-β2) and Smad3 in human gliomas associated with pathologic grading. Methods The expressions of TGFβ2 and Smad3 protein were detected with SP immunhistochemistry in 80 human glioma specimens. The Kapan-Meier survival curves of progression-free survival time and overall survival time in different expression levels was compared with log-rank. Results The expression of TGFβ2 and Smad3 correlated with the pathological grading (r=0.545, r=0.570, P<0.01). Both progression-free survival time and overall survival time were significantly different between low expression group and high expression group (P<0.05). Conclusion Both TGF-β2 and Smad3 correlate well with the occurrence and differentiation of human gliomas,which help for the diagnosis, treatment and prognosis judgment．

Objective:To correlate peripheral blood hypersensitive C-reactive protein (hs-CRP) with cognitive function in patients with depression.Methods:Seventy-five patients with depression who received treatment in the Second People's Hospital of Lishui from January 2019 to May 2020 were included in the depression group. An additional 50 healthy controls were included in the control group. The MATRICS Consensus Cognitive Battery (MCCB) was used to evaluate participates' cognitive function. Serum hs-CRP level was determined using enzyme-linked immunosorbent assay.Results:Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in the depression group were significantly lower than those in the control group ( t = 10.774, 2.774, 9.840, 5.064, 7.915, all P < 0.01). Serum hs-CRP level in the depression group was significantly higher than that in the control group [(13.05 ± 2.94) mL vs. (1.13 ± 0.18) mL, t = 28.595, P < 0.01]. Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in patients with moderate and severe depression were significantly lower than those in patients with mild depression. Serum hs-CRP level in patients with moderate and severe depression was (10.41 ± 2.21) mg/L and (25.71 ± 4.04) mg/L, respectively, which was significantly higher than that in patients with mild depression [(3.03 ± 0.49) mg/L, t = 3.015, 3.370; 3.903, 3.441; 3.541, 3.604; 4.503, 4.661; 4.001, 3.980; 4.035, 3.669, all P < 0.01]. Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in patients with severe depression were significantly lower than those in patients with moderate depression ( t = 8.331, 5.227, 10.031, 6.003, 9.416, all P < 0.01). Serum hs-CRP level in patients with severe depression was significantly higher than that in patients with moderate depression [(25.71 ± 4.04) mg/L vs. (10.41 ± 2.21) mg/L, t = 11.005, P < 0.01]. Pearson correlation analysis showed that serum hs-CRP level in patients with depression was remarkably negatively correlated with speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores (all P < 0.01). Conclusion:Serum hs-CRP level in patients with depression is greatly increased, can reflect the severity of depression and is related to cognitive function.

OBJECTIVETo evaluate the efficacy of ligation of intersphincteric fistula tract (LIFT) in the treatment of complex fistula-in-ano.

METHODSClinical data of 24 patients with complex fistula-in-ano who treated with LIFT in the Affiliated Hospital of Nanjing University of Chinese Medicine from September 2009 to February 2012 were analyzed retrospectively. The operative efficacy and postoperative continence were evaluated.

RESULTSThe prime success rate of fistula healing was 66.7% (16/24) after the LIFT procedure. Two patients presented with intersphincteric incision infection which was successfully treated with topical of silver nitrate. Four patients had intersphincteric fistula with infection and managed with the complete laying open approach. The total clinical healing rate was 91.7% (22/24). Another 2 patients had persistent external opening with discharge. During follow-up of 6 to 44 (median 16) months, The Cleveland Clinic Florida Fecal Incontinence score revealed that no patient developed decreased continence.

CONCLUSIONLIFT is a safe and effective sphincter-preserve procedure for complex fistula-in-ano.

Objective To summarize the magnetic resonance imaging (MRI) features of the persistcnt perineal sinus (PPS).Methods The retrospective and descriptive study was conducted.The clinical data of 7 patients with PPS who were admitted to the Nanjing University of Traditional Chinese Medicine between July 2010 and January 2017 were collected.Patients received horizontal,anteroposterior axes and coronal scanning of MRI after abdominoperineal resection (APR) of rectal cancer.Two physicians read collectively films and then achieved consistent results if there was a disputed result.Observation indicators:(1) MRI features;(2) treatment and follow-up situations.Patients underwent resection of PPS according to results of MRI examination,and then regular pathological examination.Follow-up using telephone interview was performed to detect sinus recurrence and reoperation up to April 2017.Results (1) MRI features:① Lesion location:lesions of PPS in 7 patients were located at the presacral areas,top side was up to the third sacral plane,and lower side extended down to the pubic area.② Morphology and signal:sinus tract of 7 patients showed irregular flaky and tubular abnormal signals;fibrotic sinus tract wall showed low signals in T1 weighted imaging (T1WI) and T2WI;contents of sinus tract in 7 patients showed low signal in T1WI and high signals in T2WI and T2WI-fat suppression (T2WI-FS).Of 7 patients,uniform signal and mixed signal were respectively detected in 2 and 5 patients.③ Branches and cystic spaces:1 patient had a branch at the tip of the coccyx,extending to the rear of the sacral vertebra.The top of sinus tract in 4 patients enlarged to form a cavity.④ Signs of infection:signs of infection in 3 patients included blurred and exuded fat gaps around the sinus tract,unclear and partially adhesion with pelvic organ;the pelvic floor muscles in 1 patient were thickened and swollen,with a high signal in T2WI-FS;flaky fluid shadows in 2 patients were seen in the posterior sinus,with a high signal in T2WI-FS,showing a tissue edema of anterior sacrum.⑤ Enhancement features:result of MRI examination of 1 patient showed mild and heterogeneous enhancement of sinus.(2) Treatment and follow-up situations:among 7 patients undergoing sinus resection,2 received curettage of superior sinus due to high location,and 5 received successfully operation.All patients underwent postoperatively regular antibiotic therapy.The healing time was 14-78 days,with an average time of 42 days.The postoperative pathological examination showed different degrees of inflammatory cell infiltration.Seven patients were followed up for 2-74 months,with an average time of 40 months.Of 7 patients,sinus in 6 patients was healed,1 had recurrence of sinus and didn't receive therapy.Seven patients didn't undergo debridement or transposition of skin flap again.Conclusion The MRI imaging features of PPS includes flaky and tubular abnormal signal in the the anterior sacrum,low signal in T1WI,high signals in T2WI and T2WI-FS,and the enhanced scanning of sinus duet shows mild and heterogeneous enhancement.

Objective To evaluate the efficacy of ligation of intersphincteric fistula tract (LIFT) in the treatment of complex fistula-in-ano. Methods Clinical data of 24 patients with complex fistula-in-ano who treated with LIFT in the Affiliated Hospital of Nanjing University of Chinese Medicine from September 2009 to February 2012 were analyzed retrospectively. The operative efficacy and postoperative continence were evaluated. Results The prime success rate of fistula healing was 66.7%(16/24) after the LIFT procedure. Two patients presented with intersphincteric incision infection which was successfully treated with topical of silver nitrate. Four patients had intersphincteric fistula with infection and managed with the complete laying open approach. The total clinical healing rate was 91.7%(22/24). Another 2 patients had persistent external opening with discharge. During follow-up of 6 to 44 (median 16) months, The Cleveland Clinic Florida Fecal Incontinence score revealed that no patient developed decreased continence. Conclusion LIFT is a safe and effective sphincter-preserve procedure for complex fistula-in-ano.

Objective To evaluate the efficacy of ligation of intersphincteric fistula tract (LIFT) in the treatment of complex fistula-in-ano. Methods Clinical data of 24 patients with complex fistula-in-ano who treated with LIFT in the Affiliated Hospital of Nanjing University of Chinese Medicine from September 2009 to February 2012 were analyzed retrospectively. The operative efficacy and postoperative continence were evaluated. Results The prime success rate of fistula healing was 66.7%(16/24) after the LIFT procedure. Two patients presented with intersphincteric incision infection which was successfully treated with topical of silver nitrate. Four patients had intersphincteric fistula with infection and managed with the complete laying open approach. The total clinical healing rate was 91.7%(22/24). Another 2 patients had persistent external opening with discharge. During follow-up of 6 to 44 (median 16) months, The Cleveland Clinic Florida Fecal Incontinence score revealed that no patient developed decreased continence. Conclusion LIFT is a safe and effective sphincter-preserve procedure for complex fistula-in-ano.