Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

Granulocytic sarcoma of breast:clinical histopathologic and biological behavior / 中华内分泌外科杂志

granulocytic sarcoma (GS) is rare in the breast, histologically and immunophenotypically similar to myelogenous leukemia, radiologically lacking specificity, similar to breast cancer or mammary abscess. It should not be misdiagnosed as invasive cancer, especially in the case of frozen diagnosis, leading to excessive surgery. Three cases of GS were collected, specimens were fully drawn, microscopic pathologic examinations and immunohistochemistry (SP method) granulocytic sarcoma of breast were performed. The clinicopathological, immunohistochemical features, diagnosis and prognosis of GS are discussed to improve the awareness of the disease.

Recent advances of microneedles for biomedical applications: drug delivery and beyond

The microneedle (MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing (3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.

Granular cell tumor of breast: clinicopathological and biological behavior / 中华内分泌外科杂志

Objective To investigate the clinicopathological and immunohistochemical features,diagnosis and prognosis of granular cell tumor of breast (GCT)and to improve the awareness of the disease.Methods Three cases of GCT were collected;Specimens were fully drawn,microscopic pathologic examinations and immunohistochemistry (SP method)were performed.Results Three cases were female patients aged from 39 to 56 years old (average 46 years).In clinical,a single indolent or indolent mass with a hard texture was located in the breast parenchyma.In pathological,the lump was mainly solid or hard tumor with clear boundary or infiltration,with a mean diameter of 2.1 (1.2-3.0)cm,and grey to yellow sections.Histologically,large cells were round or polygonal in shape.The cytoplasm was abundant and eosinophilic.The boundary of the tumor was clear in one case,and in the other two cases,the boundary was unclear.The nucleus was small and located in the center or ectopic.The cytoplasm was coarse-grained with s-100 staining positive microparticles and PAS reaction positive (anti-digestive enzymes).Immunohistochemistrically,the tumor cells were strongly positive for S-100,CD56,NSE and Vimentin,and negative for CK and SMA.None of the patients had present malignant transformation or metastasis.Conclusions GCT can occur in any part of the body,but is not common in breast.GCT is similar to breast cancer in clinical manifestations,imaging and macroscopic observation,etc.The correct diagnosis of this lesion depends on HE morphology,immunohistochemistry and special dyeing.The close postoperative follow-up should be performed.

The relationship between PLAGL1 methylation level and the risk of abnormal growth:a meta-analysis / 国际儿科学杂志

Objective Studies and researches have indicated that the methylation level of PLAGL1 differentially methylated region (DMR) was associated with some development disorder syndromes.This project is purposed to prove whether methylation levels of PLAGL1 DMR is related to the fetal and early postnatal development.Methods We performed a meta-analysis of the published data on PLAGL1 DMR methylation levels in children with developmental disorders compared with that in normal children.Results PubMed,Medline,EMBASE,WanFang databases were systematically searched to identify relevant studies.We included 7 studies in this meta-analysis,with a total of 195 cases and 438 controls concerning 6 kinds of developmental disorder syndromes.The methylation level of PLAGL1 DMR was lower in children with abnormal growth (excess growth or retarded growth) than that in normal children,with a pooled percentage mean methylation difference (95％ confidence intervals) of-1.05 (-1.93,-0.17).On this basis,we analyzed the odds ratio (95％ confidence intervals) of hypomethylation of PLAGL1 DMR in abnormal growth children in comparison with normal children.The combined odds ratio (95％ confidence intervals) of hypomethylation in abnormal growth children is 2.18 (1.23,3.88) in comparison with normal children.Conclusion Hypomethylation of PLALG1 is actually a risk factor of suffering abnormal growth for children.

Clinicopathological features and prognostic factors of apocrine carcinoma of breast / 临床与实验病理学杂志

Purpose To investigate the clinicopathologic features and prognostic factors of apocrine carcinoma ( AC) of breast. Meth-od Clinical data of 70 ACs and 283 invasive carcinomas, not otherwise specified were collected. Differences between the prognostic outcomes of the two groups were compared, and the relationship between clinicopathological characteristics and prognosis was also ana-lyzed. Results The mean age of the patients with AC (56. 17 ± 12. 41 years) was older than those with invasive carcinoma not other-wise specified (52. 77 ± 11. 07 years) (P=0. 039). The patients with AC had a lower frequency of axillary nodal metastasis, a lower frequency of ER and PR positivity comparing to invasive carcinoma not otherwise specified ( P<0. 05 ) . No significant differences in the overall survival (P=0. 221) and disease-free survival (P=0. 378) periods of the two groups were observed. Kaplan-Meier surviv-al analysis showed tumor size, lymph node metastasis, pathological stage, lymph node tissue infiltration were related with prognosis of patients with AC ( P<0. 05 ) . In multivariate analysis, lymph node metastasis was associated with a worse prognosis ( P<0. 05 ) . Conclusions Although AC and invasive carcinoma not otherwise specified have different clinicopathologic characteristics, the prog-noses of patients with these diseases are similar. Lymph node metastasis could be used as an independent factor for predicting the prog-nosis of patients with AC, early diagnosis and early treatment is the key to improve its prognosis.

Study on aldehyde dehydrogenase-1 tumor cells in invasive micropapillary carcinoma of the breast / 中华内分泌外科杂志

Objective To investigate the expression of tumor stem cell marker aldehyde dehydrogenase -1 (ALDH-1)in primary tumor and lymph node metastases of lymph node-positive invasive micropapillary carcinoma ( IMPC) of breast and its clinical significance .Methods The expression , location and distribution of ALDH-1 were examined by immunohistochemical staining in 103 cases with lymph node metastasis of IMPC and 110 cases with lymph node metastasis of invasive ductal carcinoma not otherwise specified ( IDC-NOS) without preoperative chemotherapy and radiotherapy , and their relationship with clinicopathological characteristics and prognostic sig-nificance was analyzed .Results ( 1 ) The positive expression rate of ALDH-1 was significantly higher in IMPC group of primary tumor and lymph node metastases (37.9% in primary tumor, 39/103 cases;47.6% in lymph node metastases, 49/103 cases)than in IDC-NOS group(21.8% in primary tumor, 24/110 cases; 23.6% in lymph node metastases, 26/110 cases)(P<0.05).(2)Expression of ALDH-1 had a significantly positive corre-lation with tumor size , histological grade , lymph node metastasis , ER-negative status , PR-negative status , and HER2 overexpression in primary tumor and lymph node metastases of IMPC (P<0.05).(3)The disease-free sur-vival of IMPC group patients was significantly shorter than that of IDC-NOS group patients(P=0.003).In IPMC patients with lymphode metastases , the disease-free survival of patients with ALDH-1 positive in primary tumor and lymph node was significantly lower than patients with ALDH-1 negative expression (P<0.05).In multivari-ate analysis, positive expression of ALDH-1 in metastatic lesions was associated with worse prognosis ( P =0.005).Conclusion ALDH-1 can be used as an independent factor for predicting prognosis of patients with lymph node-positive breast IMPC and the existence of stem cells in IMPC tumor cells may represent high IMPC lymphatic invasion , lymph node metastasis and high resistance .

Promoter detection and transcriptional analysis of the spinosad biosynthetic gene cluster / 生物工程学报

Spinosad represents a new class of insecticides produced by Saccharopolyspora spinosa. To understand the transcription of the spinosad biosynthetic gene cluster, two promoter detection plasmids based on different reporter genes were constructed and used to detect 9 promoters in the spinosad biosynthetic gene cluster. In addition, the temporal transcriptional profiles of the corresponding genes controlled by the 9 promoters, together with 4 genes outside of the spinosad cluster but are required for the synthesis of sugars in spinosad, were examined by real-time PCR. The results indicate that the 9 spinosad biosynthetic genes were highly expressed at the stationary phase, which coincides with the accumulation of spinosad in the fermentation broth. Of particular note is that the transcription of the 4 sugar synthetic genes showed higher level at the exponential phase, suggesting the expression of sugar synthetic genes is not correlated with the spinosad synthetic genes. The data suggest that spinosad biosynthesis could be improved by engineering the expression pattern of the sugar synthetic genes that lie outside the spinosad gene cluster.

The value of CT score in predicting surgical methods and difficulty of hepatic cystic echinococcosis / 中华放射学杂志

Objective To evaluate the value of MSCT scores on surgery method selection and its difficulty estimation for hepatic cystic echinococcosis. Methods Based on the CT features of hepatic cystic echinococcosis ( HCE), an integral system including 7 items wasestablished. Images of preoperative CT examination performed on 71 cases of hepatic cystic echnococcosis were retrospectively analyzed by the integral system and compared with actual surgical. Total 93 cystic lesions were divided into 3 groups based on CT scores: Group A suitable for total cystectom (0 to 5 score), Group B suitable for subtotal cystectom (6 to 10 score), and Group C suitable forendocystectomy ( ≥11 scores, or4 score in one item). Spearman rank correlation was used to analyze the relationship between WHO classification of cystic echinococcosis and actual surgery methods, the relationship between operation mode forecasted by CT scores and actual surgery methods, the relationship between vessel scores of cyst and actual surgery methods, and that between biliary score of cyst and actual surgery methods. Fisher exact test and Chi-square test were used to evaluate the incidence of residual cavity in patients with different biliary scores. Results Thirty nine cysts got 0 to 5 scores, 45 cysts got 6 to 10 scores and 9 cysts got more than 10 scores. Total cystectom was performed on 30 cysts, subtotal cystectomy on 40 cysts and performed endocystectomy on 23 cysts, actually. Actual operation methods were correlated with that predicated by CT scores ( r = 0. 741, P ＜ 0. 01 ), and with vessels score and biliary score (r = 0. 587,0. 327 respectively,P ＜ 0. 01 ). The higher the biliary score, the higher the incidence of postoperative biliary tract complications. Conclusions Preoperative CT scoring was an easy and objective way to accurately predict the surgery methods and its difficulty for hepatic cystic cnechnococosis.

Preoperative multi-slice spiral CT evaluation of involvement of vessels and biliary ducts in hepatic cystic echinococcosis / 中华放射学杂志

Objective To analyze the MSCT imaging of vascular and biliary ducts affected by hepatic cystic enchionococcosis disease(HCD),and to evaluate the 3D image reconstruction of MSCT.Methods Forty four cases with HCD confirmed by radical surgery were collected in this study.All cases underwent multi-phase scanning with 64-slices CT,and 3D image reconstruction of hepatic vessels was performed.Three cases suspected of bile duct complications were examined with negative CT cholangiography.All the imaging data were acquired before surgery.The spatial relationships between the cysts and the neighbor vessels and(or)bile ducts were compared with the findings during operation,then consistency was tested.Results Altogether 46 lesions were detected by MSCT before surgery.All lesions were found and diagnosed correctly,including 3 lesions rupturing into biliary duct Compared with surgery findings,the spatial relationships between lesions and the vessels were entirely consistent in first grade portal vein(14 cases)and inferior macular vein(18 cases).The Kappa values were 0.8805,0.6087,0.7751,0.7392 for first grade hepatic artery,second grade hepatic artery,second grade portal vein and hepatic vein.The relationships between bile ducts and lesions also matched in 3 bile-duct fistula cases.Conclusions MSCT with its 3D technique showed a high accuracy in the assessment of spatial relationship between vessels,biliary duct and lesions.It provides comprehensive imaging information for surgery.

Effects of Resveratrol on Cell Growth,Migration,and Invasion of Breast Cancer Cell Line MDA-MB-231 / 中国医科大学学报

Objective To investigate the effects of resveratrol on cell growth,migration,and invasion of human breast cancer cell line MDAMB-231.Methods MTT assay and soft agar colony formation assay were used to detect the effects of resveratrol on cell growth.The effects of resveratrol on cell migration and invasion were determined by Transwell migration assay and Transwell invasion assay.respectively.Results Resveratrol(25 to 200 μmol/L)inhibited the growth of MDA-MB-231 cells in a time-and concentration-dependent manner(P＜0.01).The colony formation rate of MDA-MB-231 cells decreased with the increase in the concentrations of resveratrol.After being treated with resveratrol of 25,50,100 and 200 μmol/L for 24 hours,the invasive and migratory ability of MDA-MB-231 cells was significantly inhibited (P＜0.01).Conclusion Resveratrol could inhibit the growth of MDA-MB-231 cells,and the invasive and migratory ability of MDA-MB231 cells is also inhibited by resveratrol through degrading extracellular matrix.

Imaging of the intrabiliary rupture of hepatic bydatid cysts / 中华放射学杂志

rabiliary rupture of hepatic hydatid cysts;MRCP is an effective and noninvasive diagnostic tool ;ERCP is the gold standard in confirming intrabiliary rupture of liver hydatid disease.

Determination of Impurities in High Pure Neodymium Oxide with Inductively Coupled Plasma Mass Spectrometry / 分析化学

A method for the determination of impurities in high pure Nd_2O_3 employing inductively coupled plasma mass spectrometry(ICP-MS) was established, and emphasise was put on the elimination of matrix induced NdO~+ and NdOH~+ spectral interferences using cell collision technology(CCT). Using 10% O_2-10% Ar-80% He as the reaction/collision gas and with proper adjustment of the instrumental parameters, ~(159)Tb,~(165)Ho,~(163)Dy could be quantified at ~(175)TbO,~(179)DyO and ~(181)HoO respectively, while the matrix induced NdO~+ and NdOH~+ spectral interferences could be reduced by 25-70 folds. In addition, different elements were tested as internal standards for matrix effect correction under the CCT mode, and it was found that Re was best. Other impurities including La, Ce, Sm, Eu, Gd, Er, Tm, Yb and Lu were detected under conventional mode, except that Pr was detected under high instrumental resolution mode to eliminate peak tailing interference from Nd. In combination with mathematic correction, the established method can be applied for the determination of impurities in 99.999% Nd_2O_3 products with satisfactory RSDs and recoveries.