Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Objective:To investigate the clinical value of zoledronic acid in improving the prognosis of osteoporotic hip fracture and preventing its sequential contralateral hip fracture.Methods:A retrospective study of 206 patients diagnosed with hip fragile fractures in China Medical University Affiliated Shengjing Hospital and treated with anti-osteoporotic drugs after surgery was conducted. The prognosis of patients with hip fracture using survival rate analysis and the risk factors of acute febrile complications with multivariate analysis after zoledronic acid treatment were evaluated. Furthermore, chi-square test and multivariate analysis was used to explore whether zoledronic acid decreases the occurrence of the contralateral sequential fracture.Results:The 3-year survival rate of patients with overall hip fracture was higher in zoledronic acid treatment group compared with control group( P=0.026), with the incidence of fever at 53.3%. The age [ OR=0.786, P=0.027, the area under receiver operating characteristic (ROC) curve was 0.724] and cardiopulmonary complications ( OR=0.043, P=0.025, the area under ROC curve was 0.628) were significantly correlated with the occurrence of acute febrile response. The incidence of sequential contralateral fractures in zoledronic acid treatment group was significantly lower than that in control group ( χ2=4.356, P=0.037). The application of zoledronic acid ( OR=0.160, P=0.007, the area under ROC curve is 0.586) and the type of femoral neck fracture ( OR=0.196, P=0.001, the area under ROC curve is 0.607) were statistically associated with the occurrence of sequential fractures. Conclusion:Zoledronic acid treatment improves the outcome of patients with osteoporotic hip fracture and reduces the incidence of sequential hip fractures, especially femoral neck fracture. Senile age and cardiopulmonary complications might be associated with lower risk of acute febrile reactions after zoledronic acid treatment.

Objective:To observe the changes of nutrition impact symptoms (NIS) and fat-free mass and analyze the relationship between them in patients with head and neck cancer (HNC) during radiotherapy.Methods:A convenient sampling method was adopted to select HNC patients who received radiotherapy in the outpatient clinic of department of radiotherapy for head and neck cancer in a cancer hospital in Beijing from March 2017 to January 2020. The nutrition impact symptoms (NIS) were assessed by a nutrition impact symptoms checklist and the fat free mass was assessed by bioelectrical impedance analysis at three time points: before radiotherapy (T1), during radiotherapy (T2) and at the end of radiotherapy (T3). The Generalized Estimating Equations (GEE) was used to analyze the relationship between them.Results:A total of 542 HNC patients were included in the analysis. During radiotherapy, the patients' NIS number and score presented an increasing trend, reaching the highest level and peaked at the end of radiotherapy. The change of fat-free mass showed a decreasing trend and reached the minimum at the end of radiotherapy. Patients with higher NIS scores had more percentage loss of fat-free mass.Conclusions:During radiotherapy, patients with HNC showed an increase in NIS score and lost fat-free mass. Patients with higher NIS score lost more percentage of fat-free mass, which suggested that clinical medical staff should pay attention to NIS management and take comprehensive intervention measures in time to reduce the loss of fat-free mass.

To study the clinical effect of non-ampullary duodenal mucosal lesions treated by endoscopic resection. A retrospective analysis was performed on the data of 58 cases of duodenal non-ampullary mucosal lesions treated by endoscopic resection from January 2016 to June 2019 from 3 hospitals. Among 58 cases, 27 lesions (46.6%) were located in the duodenal bulb and 31 (53.4%) in the duodenal descending part (including the ball-drop boundary). Forty-six patients (79.3%) received endoscopic mucosal resection, 7 (12.1%) received endoscopic submucosal dissection and 5 (8.6%) received pre-cut endoscopic mucosal resection. Few postoperative complications were found except for 1 case of intraoperative bleeding, 1 case of delayed bleeding 2 days after surgery, 1 case of lesion residual and 2 cases of postoperative abdominal pain. No perforation occurred. Endoscopic treatment of non-ampullary duodenal mucosal lesions is safe and effective.

Objective:To investigate the indication of pre-cut-endoscopic mucosal resection (pre-cut-EMR) on the treatment of colorectal laterally spreading tumors (LSTs).Methods:A retrospective study was performed on data of colorectal LSTs patients, who underwent pre-cut-EMR in Wuxi Second People’s Hospital and Zhongshan Hospital from January 2014 to June 2019. The relationships between the clinical characteristics of the lesions and the success rate and complications of pre-cut-EMR were analyzed.Results:Data of 132 colorectal LSTs cases were included in the study. Morphology of 29 (22.0%) LSTs were homogeneous granular type, 43 (32.6%) LSTs were mixed non-granular type, 58 (43.9%) LSTs were flat elevated type, and 2 (1.5%) LSTs were pseudo-depressed type. The diameter of lesions was 2.3±1.5 cm (ranged from 2.0 cm to 5.0 cm). Among the 132 LSTs, 36 (27.3%) tumors were located in rectum, 15 (11.4%) in sigmoid colon, 10 (7.6%) in descending colon, 17 (12.9%) in splenic flexure of colon, 21 (15.9%) in transverse colon, 24 (18.2%) in hepatic flexure of colon, 6 (4.5%) in ascending colon, and 3 (2.3%) in cecum. The histopathological diagnoses of the 132 LSTs included low grade intraepithelial neoplasia in 58 cases (43.9%), high grade intraepithelial neoplasia in 69 cases (52.3%), intramucosal carcinoma in 2 cases (1.5%), and canceration in 3 cases (2.3%). Pre-cut-EMR was achieved in all 132 patients, and the operation time was 25.3±13.6 min (ranged 20-65 min). The rate of en bloc resection and complete resection were 95.5% (126/132) and 100.0% (132/132), respectively. Two cases (1.5%) had intraoperative perforation, and were both located in the sigmoid colon with the diameter of 4.0 cm and 4.5 cm, respectively. Twelve cases (9.0%) had immediate bleeding during operation, and 2 cases (1.5%) had delayed bleeding after operation. Patients had been followed up for 6-24 months, the wound healed well after operation, and no local recurrence was found.Conclusion:Pre-cut-EMR is an effective and safe therapy for colorectal LSTs with diameter less than 4.0 cm.

Objective To describe the characteristics of radiation induced mucositis in patients withhead and neck cancer ( HNC) during radiotherapy, and analyze the effect of radiation induced mucositis on diet patterns and weight change and the influencing factors for radiation induced mucositis. Methods Patients with HNC treated with radiotherapy in one cancer hospital were recruited. Data were collected before, during and at the end of the radiotherapy, which included radiation induced oral and pharyngeal mucositis, pain during eat-ing, diet patterns and weight. Results Two hundred and two patients were completely investigated and 43.5％and 34. 2％ of the patients suffered from moderate to severe (≥grade 2) oral mucositis and pharyngeal mucosi-tis, respectively during the radiotherapy. At the end of radiotherapy, 53. 5％ and 51. 5％ of the patients suffered from moderate to severe oral mucositis and pharyngeal mucositis (≥grade 2 ) , respectively. Oral and pharyngeal mucositis were significantly correlated with pain during eating, diet patterns and weight ( P<0. 05) . Tumor site was the main reason that affected the severity of mucositis ( Wald χ2 =26. 033, 14. 216;P<0.001). Conclusion Radiation induced mucositis was gradually aggravated with radiotherapy progress, which is closely related to pain during eating, change of diet patterns and weight loss. The severity of mucositis is re-lated to the tumor site. Measures should be taken to strengthen the management of adverse reactions and nutri-tional status of patients.

Objective To describe the characteristics of dysphagia in patients with head and neck cancer during radiotherapy,and analyze the cause of dysphagia and the relationship between dysphagia and weight change.Methods Patients with head and neck cancer treated with radiotherapy in Beijing Cancer Hospital from November 2017 to June 2018 were recruited.The M.D.Anderson Dysphagia Inventory (MDADI) was used to assess the dysphagia of patients before (T1),during (T2) and at the end (T3) of the radiotherapy.Meanwhile,the weight,dietary intake and radiation adverse effects were investigated.Generalized estimating equations were used to analyze the impact factors of dysphagia and the relationship among dysphagia,dietary intake and weight change.Results Ninety-six patients were completely investigated and the incidence of dysphagia were 6.3％ (6/ 96),80.2％ (77/96) and 85.4％ (82/96) in T1,T2 and T3.With the progress of radiotherapy,the total score and the scores of 4 dimensions of MDADI dropped and the dietary intake declined.The average weight loss was (5.09±3.31) kg,and 76.1％ of the patients had weight loss over 5％ at the end of radiotherapy.The occurrence of dysphagia was associated with the radiotherapy-related oral and laryngeal mucositis and the weight loss was closely associated with the site of radiation,dysphagia,and dietary intake decline.Conclusions The dysphagia of patients with head and neck cancer is affected by radiation adverse effects,and is most severe at the end of radiotherapy.Dysphagia might result in dietary intake decline and weight loss.Clinicians should pay close attention to the swallowing function of the patients and take measures earlier accordingly.

OBJECTIVETo analyze the risk factors of carcinogenesis of large colorectal polyps (diameter ≥ 10 mm) found by colonoscopy.

METHODSClinicopathological and follow-up data of 418 consecutive patients who were diagnosed as colorectal polyps with diameter≥10 mm by colonoscopy at two endoscopy centers of the Affiliated Wuxi Second People's Hospital, Nanjing Medical University (n=207) and Zhongshan Hospital, Fudan University (n=211) from January 2015 to December 2016 were retrospectively collected. High-grade intraepithelial neoplasia and cancer were defined as malignancy in this study. Chi square test was used for univariate analysis, and logistic regression was used for multivariate analysis (in patients with multiple polyps, if the pathological findings were all low grade intraepithelial neoplasia, one polyp with the largest diameter was selected to enter the model; in patients with high grade intraepithelial neoplasia, one polyp of high grade intraepithelial neoplasia with the largest diameter was selected to enter the model). Associated risk factors of malignancy were analyzed.

RESULTSAmong the 418 patients, 278(66.5%) were male and 140(33.5%) were female, with mean age of (58.7±10.2) (range 15-87) years old. Of 398 patients undergoing endoscopic treatment with resected 456 polyps, 142 cases with 150 polyps were malignant, including 134 polyps of high-grade intraepithelial neoplasia and 16 polyps of intra-mucosal cancer. The other 20 patients showed negative elevation signs after endoscopic submucosal injection and were transferred to surgery, of whom 20 polyps were resected. Histological examination of these 20 polyps indicated invasive cancer. Univariate analysis showed that age ≥ 50 years [40.5% (150/370) vs. 25.0% (12/48), χ² =4.323, P=0.041], multiple polyps [77.5%(31/40) vs. 34.7%(131/378), χ² =12.900, P=0.001], polyp locating at rectum [59.0%(36/61) vs. 32.3%(134/415), χ² =22.736, P=0.000], polyp diameter ≥31 mm [74.1%(20/27) vs. 33.4%(150/449), χ² =36.493, P=0.000] and tubular villous adenoma [67.4%(120/178) vs. 16.8%(50/298), χ² =71.810, P=0.000] were associated with malignancy. Multivariate analysis showed that age ≥ 50 years(OR=2.473, 95%CI:1.209-5.058, P=0.013), multiple polyps (OR=2.472, 95%CI: 1.300-4.702, P=0.006), polyp locating at rectum (OR=1.253, 95%CI: 1.091-1.439, P=0.001) and the polyp diameter ≥31 mm (OR=1.500, 95%CI:1.196-1.881, P=0.000) were independent risk factors for malignancy of large colorectal polyps. The mean follow-up time was (9.6±4.2) months. During the follow-up period, 86 patients (20.5%) who received endoscopic resection developed recurrent adenoma which all were successfully removed by colonoscopic polypectomy. Two patients(0.5%) developed colon cancer 6 months after endoscopic resection and both underwent radical surgery and chemotherapy. Their previous pathology from endoscopic resection was tubular villous adenoma and high grade intraepithelial neoplasia. All the patients were alive during the follow-up period.

CONCLUSIONSAge ≥50 years old, multiple polyps, polyps locating at rectum and polyps with diameter ≥ 31 mm are the risk factors of malignancy. Emphasized examination should be recommended for those with the above mentioned risk factors to avoid missed diagnosis and misdiagnosis. The choice of endoscopic treatment must be reasonable for curative resection.

Objective To study the effect of human umbilical cord mesenchymal stem cells (hMSCs) on the survival rate of mice with radiation-induced intestinal injury and its effect on the repair of intestinal damage.Methods Adult C57BL/6J mice were selected and divided into control group and abdomen irradiation + PBS(IR + PBS) group and abdominal irradiation+hMSCs transplantation treatment (IR+hMSCs)group.Intestinal injury model was induced by abdominal irradiation at 13 Gy of T ray and the 30-day survival rate was recorded.On the 3.5th and 5.0th day after irradiation,HE staining was used to observe changes in the villus structure and thc number of intestinal crypts in each segment of the small intestine (duodenum,jejunum,and ileum).Results The survival rate of IR+hMSCs group was significantly higher than that of IR+PBS group (P＜0.05).On the 3.5th day after 13 Gy of abdomen irradiation,the duodenum,cavities and ileum villus in IR+PBS group were all fractured,the length was shortened,and the numbers were sparse when compared with the control group,while the hMSCs reduced the intestinal damage.On the 5.0th day after irradiation,the structural integrity of the small intestine in IR+PBS group was repaired slightly,but it still more serious than that of IR+hMSCs group (P＜0.01).The amount of intestine crypts were significantly higher in IR+hMSCs group than that of IR+PBS group,but were significantly lower than that of control group (P＜0.01) at 3.5th day and 5.0th day after radiation.Conclusion Transplantation of hMSCs can improve the survival rate and promote the repairation of intestinal injury induced by radiation in mice.MSCs are hopeful to be used on the treatment of radiation-induced intestinal injury.

Objective To investigate the induction of B-cell specific phenotype in classical Hodgkin lymphoma (cHL)upon all-trans retinoic acid(ATRA)incubation. Methods To construct B-cell specific promoter(CD19, CD79a,CD79b)driven reporter plasmid with NEO cassette to realize stable transfection and selection of cHL reporter cells. To verify the intact integration by amplification of the promoter and luciferase sequences,and to functionally validate the B-cell specific promoter by ABF1 interference and luciferase assay. Repoter cells were incubated with various doses of ATRA and luciferase activity was detected at 24,48 and 72 hours. Reporter cells were treated alone or in combination with 5-Aza and ATRA followed by luciferase assay. Endogenous B-cell specific genes(CD19, CD20, CD79a and CD79b) transcription and expression levels were detected by real-time PCR and immunoblot, respectively. The expression level of CD30 antigen on Hodgkin lymphoma cell membrane upon ATRA was assessed by flow cytometry. Results ATRA treatment stimulated B-cell specific signature in cHL cells including CD19,CD79a and CD79b while down-regulated their CD30 expression. Conclusions ATRA induces B-cell phenotype deficient cHL cells to regain their B-cell transcriptional program while abolishes their Hodgkin-specific machinery.