Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective Building a TCM health management and clinical research integration platform for knee osteoarthritis,promoting the integration of traditional Chinese medicine with internet and mobile health technology,driving the digitalization of TCM-enabled knee osteoarthritis health management strategies,and providing a convenient digital platform for the efficient conduct of TCM clinical research on knee osteoarthritis.Methods Using a combination of literature review and market research,a preliminary framework for the platform's functions and services was established.Then,17 patients with knee osteoarthritis were interviewed through a convenient sampling method to identify their needs and preferences,and design the platform's functional modules and service flow.In the development and testing phase,a multidisciplinary team consisting of professional development engineers,data scientists,and clinical experts conducted multiple rounds of discussions to ensure the scientificity,feasibility,and convenience of the platform's function and service development.Results The integrated platform of traditional Chinese medicine health management and clinical research for knee osteoarthritis is built.The traditional Chinese medicine health management module includes features of health education,evaluation and exercise training,etc.The scientific research module includes patient self-report outcome data collection and remote quality control,etc.,which can provide the whole process service integrating health management and remote intelligent clinical trial.Conclusion Building an integrated platform of TCM health management and clinical research will provide more convenient and effective health management solutions for patients with knee osteoarthritis.

Objective Building a TCM health management and clinical research integration platform for knee osteoarthritis,promoting the integration of traditional Chinese medicine with internet and mobile health technology,driving the digitalization of TCM-enabled knee osteoarthritis health management strategies,and providing a convenient digital platform for the efficient conduct of TCM clinical research on knee osteoarthritis.Methods Using a combination of literature review and market research,a preliminary framework for the platform's functions and services was established.Then,17 patients with knee osteoarthritis were interviewed through a convenient sampling method to identify their needs and preferences,and design the platform's functional modules and service flow.In the development and testing phase,a multidisciplinary team consisting of professional development engineers,data scientists,and clinical experts conducted multiple rounds of discussions to ensure the scientificity,feasibility,and convenience of the platform's function and service development.Results The integrated platform of traditional Chinese medicine health management and clinical research for knee osteoarthritis is built.The traditional Chinese medicine health management module includes features of health education,evaluation and exercise training,etc.The scientific research module includes patient self-report outcome data collection and remote quality control,etc.,which can provide the whole process service integrating health management and remote intelligent clinical trial.Conclusion Building an integrated platform of TCM health management and clinical research will provide more convenient and effective health management solutions for patients with knee osteoarthritis.

Objective:To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) .Methods:A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed.Results:Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [ CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10 9/L, platelet (PLT) ≥450×10 9/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years ( HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl ( HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts ( P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients ( HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients ( HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions:Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.

OBJECTIVETo investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL).

METHODSA total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases.

RESULTSAtypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases.

CONCLUSIONSThe histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

Biopsy ; Bone Marrow ; pathology ; Burkitt Lymphoma ; genetics ; pathology ; Child ; Diagnosis, Differential ; Female ; Flow Cytometry ; Genes, myc ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Lymphocytes ; pathology ; Lymphoma, B-Cell ; pathology ; Lymphoma, Large B-Cell, Diffuse ; pathology ; Male ; Retrospective Studies ; Translocation, Genetic

OBJECTIVETo study the clinical and pathologic features of multiple myeloma(MM) with CCND1.

METHODSRetrospectively analyzed the clinical and pathologic profiles of 158 patients with MM from 2010 to 2013. The clinical and morphologic features of bone marrow aspiration, biopsy and immunophenotypic analysis which was carried out by flow cytometry and immunohistochemistry were analyzed in all patients with MM respectively. CCND1 translocation was studied by FISH method in all cases. Classical cytogenetic studies of bone marrow were performed in 24 cases whose CCND1 was positive.

RESULTSIn the 158 patients with MM, CCND1 was detected in 31 patients (19.6%）. In 31 patients, type IgA, IgD, IgG, IgM, light-chain only and nonsecretory MM were 4 cases,4 cases,11 cases,1 case, 6 cases and 5 cases respectively. A high incidence of CCND1 was observed in IgD and nonsecretory MM comparied with IgA and IgG respectively (P<0.05). but no statistical significance was reached between κ and λ type patients (P=0.627). The morphology of plasma cell in bone marrow biopsies were small Lymphocyte- Like 24 cases,mature plasma cell 6 cases and immature plasma cell 1 case. Immunophenotype of all 31 cases was CD38⁺CD138⁺CD19⁻CD45⁻, (CD56⁺ in 11 cases, CD20⁺ in 9 cases, CD117⁺ in 3 cases. MM with CCND1 showed a strong association with CD20 expression, the lack of CD56 expression. Immunohistochemistry showed positive for cyclinD1 in 22 cases.

CONCLUSIONA high incidence of CCND1 was detected in the IgD and nonsecretory MM, and correlated with Small Lymphocyte- Like, higher positive rate of CD20, cyclinD1 and the lack of CD56 expression. MM with CCND1 must be distinguished from LPL and other mature B cell lymphomas which have plasmacytoid differentiation.

Biopsy ; Bone Marrow ; Cyclin D1 ; metabolism ; Flow Cytometry ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; classification ; metabolism ; Plasma Cells ; Retrospective Studies ; Translocation, Genetic

Objective To study the characteristic findings of computer tomography (CT) and magnetic resonance imaging (MRI) in hepatobiliary cystadenocarcinoma.Methods CT,MRI and clinical data were analysed retrospectively.Plain,dynamic CT and MRI were performed in all patients.Results There were 8 patients,7 female,1 male,aged 48-74 years,with a median age of 58.Five lesions were in the left liver,and 3 lesions were in the right liver.One lesion was multilocular cysts with septations.Seven lesions were solitary.The lesions showed low or mixed density on plain CT.Two cysts showed evidence of hemorrhage,while 3 cysts showed fluid levels.There were different signal intensities in the cystic wall nodules which could appear as slightly low intensity on T1WI or slightly high intensities on T2WI.The cyst wall and septations appeared as slightly low intensity on T1WI and T2WI.The cystic fluid signal intensity changed with liquid ingredients.The nodularities showed obviously high signal intensity on DWI,and the fluid showed slightly high signal,while the cystic wall and separations showed slightly low signal intensity.On CT and MRI dynamic enhancement scanning,the nodularities showed obvious enhancement on the arterial phase,while the cystic wall and separations showed no enhancement.The nodularities showed persistent enhancement on the portal venous and delayed phases while the cystic wall and separation showed slight enhancement.Conclusions Hepatobiliary cystadenocarcinoma showed characteristic features on MSCT and MRI.MSCT combined with MR is an important method in the diagnosis and differential diagnosis of hepatobiliary cystadenocarcinoma.

From theYellow Emperorand other representative Chinese classics of the Tang and its previous dynasties we assorted the contents of extracting solvent, boiling time, boiling heat and special frying methods. By studying these contents, we found that immersion can reduce side effects and improve efficacy;boiling solvents include water, vinegar and so on;6-8 times the amount of water than the drug is preferred, boiling times is usually once;special frying methods include decoction first, decoction later, decocted medicine water used in place of water as solvent, infused decoction, etc. Decoctions were generally not allowed to stand overnight. TCM decocting methods had great impacts on its effectiveness. It can provide more medication ideas for doctors and provide boiling guidance to patients.

OBJECTIVETo analyze the effects of nicotine on the bone calcium and phosphorus content and alkaline phosphatase (ALP) activity in rat alveolar bone and mandible.

METHODSTwenty health male Wistar rats of five weeks of age were randomly assigned to two groups and received daily intraperitoneal injections for three months as follows: Saline solution for control group, nicotine 0.73 mg.kg-l.d-1 for experimental group. The bone calcium phosphorus content were detected by concentrated acid digestion method and the ALP activity was examined by improved Reddi method.

RESULTSCompared to the control group, bone calcium and phosphorus content was lower in the experimental group (P<0.05), ALP activity had no statistical significance(P>0.05). Bone calcium phosphorus and ALP activity in different parts had no statistical significance (P>0.05).

CONCLUSIONThe nicotine reduces calcium phosphorus deposition of jaw bone, but has no obvious influence to ALP activity.

Alkaline Phosphatase ; Animals ; Bone and Bones ; Calcium ; Male ; Nicotine ; Phosphorus ; Rats ; Rats, Wistar

Objective To study the expression of BCSG1 ,S100A4,VEGF in human breast cancer.Methods Immunohistochemistry technique SP method was used to examine breast fibroadenoma in 40 cases,breast invasive ductal carcinoma in 62 cases ( by armpit lymph node metastasis as 2 groups) and corresponding paratumor tissues in 48 cases. Results Among the 4 groups, there was significant difference ( P＜0.05 ) in the positive immunostaining rate of BCSG1 ,S100A4, VEGF. Conclusions In the breast invasive ductal carcinoma, the expression of BCSG1, S100A4 and VEGF increased. This suggested the invasive and metastasis ability of the neoplasm enhanced. The expression were in positive correlation with tumor pathology. Combined detection of BCSG1, S100A4, VEGF expression contributes to the early diagnosis and prognostic assessment of the carcinoma of the breast.