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.

OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.
Child ; Male ; Female ; Humans ; Anemia, Diamond-Blackfan/genetics* ; Pediatric Obesity/complications* ; Glucocorticoids/therapeutic use* ; Prevalence ; Risk Factors ; Ribosomal Proteins/genetics* ; Mutation

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.
Ferritins ; Humans ; Iron ; Iron Overload ; Liver/metabolism* ; Myelodysplastic Syndromes/therapy* ; Primary Myelofibrosis ; Retrospective Studies ; Splenomegaly

In this paper, a new type of preparation for treatment of initial dry eye disease, thermosensitive in situ gel, was prepared using levocarnitine as a model drug. Poloxamer 407 and poloxamer 188 were used as the gel matrix, and sodium hyaluronate and sodium carboxymethylcellulose were used as bioadhesive materials. Gelation temperature was determined by a rotor method and the prescription was optimized by central composite design-response surface methodology. The pH value, viscosity value and gelation temperature of the optimal prescription were measured. The release of the drug in vitro was examined by dialysis membrane permeation, and retention time of the thermosensitive in situ gel preparation on the rabbit's ocular surface was observed by a slit lamp microscope. The results showed that the dosage of the poloxamer 407 and poloxamer 188 were 20.81% and 3.46%, respectively, and sodium hyaluronate was 0.02%, sodium carboxymethyl cellulose was 0.10% of the optimal formulation of levocarnitine thermosensitive in situ gel. The pH value was 6.90 ± 0.06 at room temperature and the viscosity value started to rise sharply at 27 ℃ of the optimal formulation. The gelation temperature of the optimal preparation before and after dilution by simulated tear fluid were (26.37 ± 0.06) ℃ and (33.57 ± 0.21) ℃, respectively. In the first 240 min, in vitro release rate per unit area of levocarnitine thermosensitive in situ gel was lower than that of solution (P<0.05), and after 600 min, the cumulative release rate of levocarnitine thermosensitive in situ gel could reach more than 80%. The retention time of the thermosensitive in situ gel preparation on rabbit's ocular surface reached about 25 min, at least 5 times as much as that of the solution. The animal experiment was conducted following the National Institutes of Health Guidelines for the use of experimental animals, and approved by the Ethics Committee of the Experimental Animal Center of Beijing University of Chinese Medicine. The levocarnitine thermosensitive in situ gel showed good characteristics and sustained release property and significantly improved the retention time of the drug on the rabbit's ocular surface.

Objective To optimize ambi-extracting and inclusion process of volatile oil from Chuanxiong Rhizoma and Angelicae Sinensis Radix. Methods With yield ratio of volatile oil and ferulic acid content in water extract as evaluation indexes, single factor experiments were used to study the extraction process. With the inclusion rate of volatile oil and yield of inclusion as evaluation indexes, saturated aqueous solution was used to L9(34) orthogonal experiments to reach optimum inclusion process. Results The optimum extraction process of Chuanxiong Rhizoma and Angelicae Sinensis Radix was extracted for 8 hours with 8 folds the amount of water, and without soaking. The validation experiments of extraction of volatile oil and ferulic acid content in water extract were 1.23 mL and 0.387 9 mg/g. The optimum conditions of inclusion process were as follows: volatile oil (mL): β-CD (g) was 1:8;inclusion temperature was 40 ℃; inclusion time was 3 hours. The validation experiments of inclusion rate of volatile oil and yield of inclusion were 74.89% and 72.81%. Conclusion Optimum ambi-extracting and inclusion process of volatile oil from Chuanxiong Rhizoma and Angelicae Sinensis Radix are feasible and stable, witch can provide certain supporting data for preparation production.

BACKGROUND: miR-15b plays an important role in the initiation and development of tumors, based on which, we speculate that miR-15b may be involved in the migration and invasion of glioma stem cells (GSCs). However, there is no relevant report and the mechanism of action is also unclear. OBJECTIVE: To identify the effects of miR-15b on the migration and invasion of GSCs and the mechanisms involved in this process. METHODS: Quantitative PCR was performed to evaluate the expression of miR-15b in the gliomas tissues, normal brain tissues, GSCs and non-GSCs. After knockdown of ATP-binding cassette superfamily G member 2 (ABCG2) by ABCG2 specific siRNA, Transwell assay was performed to determine the effect of ABCG2 on GSCs migration and invasion. Additionally, the GSCs were transfected with miR-15b mimics or inhibitor to up-regulate or down-regulate the expression of miR-15b. At 48 hours after transfection, Transwell assay was used to detect the effect of miR-15b on GSCs migration and invasion; ELISA and gelatin zymography assays were performed to determine the matrix metalloproteinase-2/-9 (MMP-2/-9) expression and activity after treatment with miR-15b. CD133-positive or non-CD133-positive cells were directly injected subcutaneously into nude mice. Tumor formation was observed within 30 days after injection. RESULTS AND CONCLUSION: miR-15b was significantly down-regulated in gliomas tissues compared with normal brain tissues, which was negatively correlated with the stage of gliomas. In addition, miR-15b was significantly down-regulated in GSCs compared with non-GSCs. Up-regulation of miR-15b significantly reduced the migration and invasion ability of GSCs (P < 0.01), and down-regulation of miR-15b significantly enhanced the cell migration and invasion of GSCs (P < 0.01). By target prediction analysis, we obtained that ABCG2 was a potential target gene of miR-15b. Luciferase assay confirmed that miR-15b targeted ABCG2 directly, and migration and invasion of GSCs were dramatically reduced by ABCG2 siRNA (P < 0.01). ELISA results showed that up-regulation miR-15b significantly inhibited MMP-2/-9 expression. ELISA and gelatin zymography assay results showed that ABCG2 siRNA did not affect MMP-2/-9 expression, but significantly inhibited the activity of MMP-2/-9. In the in vivo tumor model, GSCs were more tumorigenic as compared with non-GSCs from the same tumor in vivo. To conclude, miR-15b regulates the migration and invasion of GSCs by targeting the ABCG2 signaling pathway, and up-regulation of miR-15b can suppress the migration and invasion of GSCs.

Objective To observe the clinical efficacy and safety of levodopa combined with entacapone in the treatment of Parkinson ’ s di-sease.Methods Fifty -four patients with Parkinson ’ s disease were randomly divided into treatment group(n=27) and control group(n=27). Control group was given levodopa 0.25 g oral, tid.Treatment group was treated with entacapone 0.2 g oral tid, on the basis of the control group . Two groups were treated for 16 weeks.The clinical efficacy , serum levels of interleukin(IL) -1β, IL-6, malonaldehyde, superoxide dismutase ( SOD) and glutathione peroxidase ( GSH-Px) , scores of unified Parkin-son’ s disease rating scale ( UPDRS) and incidence of adverse drug reac-tions were compared between two groups .Results After treatment , the total effective rate of treatment group was significantly higher than that of control group (92.59%vs 70.37%, P<0.05).After treatment, among the treatment and control group , the levels of serum IL -1βwere (32.32 ±0.32), (45.35 ±6.01)pg? L -1, IL-6 were (4.03 ±0.54), (6.78 ±0.82)pg? L-1, malonaldehyde were (14.72 ±2.21), (19.37 ±2.44)mmol? mg -1, UPDRS-Ⅱscore were (3.98 ±1.56), (11.74 ±1.25) point and UPDRS-Ⅲscore were (26.43 ±3.28), (31.54 ±4.17) point, and those indexes in treatment group after treat-ment were significantly lower than those of control group ( P<0.05 ) .After treatment , the levels of serum SOD were (135.55 ±17.84), (120.93 ±18.38)U? μg-1 and GSH-Px were (99.74 ±12.43), (90.73 ±10.84)U? μg-1 in treatment and control group , also the those indexes in treatment group after treatment were significantly higher than those in control group ( P<0.05 ).The adverse drug reactions were based on the symptoms of nervous system , diges-tive system and skin for two groups.Also, the incidence of adverse drug reactions in control group was 14.81%, treat-ment group was 11.11%, the difference had no statistically significant difference ( P>0.05 ).Conclusion Levodopa combined with entacapone have a definitive clinical efficacy for the treatment of Parkinson ’ s disease , without increasing the incidence of adverse drug reactions .

BACKGROUND: The quality of chest compressions can be significantly improved after training of rescuers according to the latest national guidelines of China. However, rescuers may be unable to maintain adequate compression or ventilation throughout a response of average emergency medical services because of increased rescuer fatigue. In the present study, we evaluated the performance of cardiopulmonary resuscitation (CPR) in training of military medical university students during a prolonged basic life support (BLS). METHODS: A 3-hour BLS training was given to 120 military medical university students. Six months after the training, 115 students performed single rescuer BLS on a manikin for 8 minutes. The qualities of chest compressions as well as ventilations were assessed. RESULTS: The average compression depth and rate were 53.7±5.3 mm and 135.1±15.7 compressions per minute respectively. The proportion of chest compressions with appropriate depth was 71.7％±28.4％. The average ventilation volume was 847.2±260.4 mL and the proportion of students with adequate ventilation was 63.5％. Compared with male students, significantly lower compression depth (46.7±4.8 vs. 54.6±4.8 mm,P<0.001) and adequate compression rate (35.5％±26.5％ vs. 76.1％±25.1％,P<0.001) were observed in female students. CONCLUSIONS: CPR was found to be related to gender, body weight, and body mass index of students in this study. The quality of chest compressions was well maintained in male students during 8 minutes of conventional CPR but declined rapidly in female students after 2 minutes according to the latest national guidelines. Physical fitness and rescuer fatigue did not affect the quality of ventilation.

OBJECTIVETo explore the effects of harmful factors in tank cabins on renal function of tank crews.

METHODSOne hundred and fifty two tank crews as the observation group and 37 soldiers without tank environment exposure as control group were selected in the study. α1-microglobulin(α1-MG), β2-microglobulin(β2-MG), IgG, N-acetyl-β-glucosidase (NAG) and urinary albumin excretion rate (UAER) in morning and 24 h urine were measured.

RESULTSCompared to the control group, the levels of α1-MG, β2-MG, NAG, UAER in observation group were increased significantly (P < 0.05). β2-MG, NAG, UAER of Soldiers with more than 50 motorized hours in observation group were significantly higher than those of control group (P < 0.05). β2-MG, NAG and UAER of soldiers divorced from tank occupation more than 3 years decreased to the normal levels. β2-MG of soldiers divorced from tank occupation more than 10 years was significantly higher than that of 6-10 years group.

CONCLUSIONTank occupational exposure influences the renal function of tank crews but not to a degree of clinical kidney disease. The renal function of crews divorced from tank occupation may recover but dysfunction of renal tubular reabsorption still exists.

Acetylglucosaminidase ; metabolism ; Albuminuria ; Alpha-Globulins ; metabolism ; Environmental Exposure ; adverse effects ; Humans ; Kidney ; physiology ; Kidney Function Tests ; Military Personnel ; beta 2-Microglobulin ; metabolism

OBJECTIVETo evaluate the effect of adjuvant hormonal therapy (AHT) immediately after radical surgery for high- risk organ-confined or locally advanced prostate cancer using the PSA-related biochemical relapse rate within 2 years after surgery.

METHODSWe retrospectively analyzed 62 cases of high-risk organ-confined or locally advanced prostate cancer. The patients were treated by laparoscopic radical prostatectomy or radical retropubic prostatectomy after MRI and ECT systemic bone imaging examination, which revealed no regional lymph node or bone metastasis. Thirty-two of the patients (group A) received AHT orally or subcutaneously from 2 weeks to 1 months after operation, and another 30 (group B) were left untreated. We followed up the patients for 2 years, measuring the serum PSA level every 3 months, performing ECT every 6 months, and recording the adverse reactions, medication dura- tion, and the patients'quality of life.

RESULTSAll the operations were successfully accomplished. The rate of 2-year biochemical relapse-free survival was 78.13% (25/32) in group A and 53.33% (16/30) in group B.

CONCLUSIONAHT immediately after radical surgery can improve the rate of biochemical relapse-free survival of the patients with high-risk organ-confined or locally advanced prostate cancer and check the progression and metastasis of the disease.

Aged ; Antineoplastic Agents, Hormonal ; therapeutic use ; Chemotherapy, Adjuvant ; Disease Progression ; Disease-Free Survival ; Humans ; Laparoscopy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; blood ; Neoplasm Staging ; Prostate-Specific Antigen ; blood ; Prostatectomy ; methods ; Prostatic Neoplasms ; blood ; drug therapy ; pathology ; surgery ; Quality of Life ; Retrospective Studies