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 To evalu ate the effects of perimenopausal one-day outpatient multidisciplinary model on the cognition of women to menopause hormone therapy （MHT）. METHODS The perimenopausal one-day outpatient service opened by the Third Affiliated Hospital of Chongqing Medical University in 2017 was introduced ，which was participated by doctors ，pharmacists， nutritionists，music psychotherapists ，nurses and other multidisciplinary members to provide systematic ，all-round，humanistic and face-to-face group science popularization and education ，practical experience and Q&A for women in perimenopause or about to enter perimenopause （called“students”）. The students who participated in one-day outpatient service in 2020 were selected as the survey object ， and the questionnaire was CMEI2020KPYJ（ZAMM）00206] designed to analyze the understanding of perimenopausal syndrome，awareness rate of MHT ，willingness to use and concerns. RESULTS A total of 295 students completed the questionnaire. Compared with before participation ， after participated in one-day outpatient service ，the cognition level of the students were all improved significantly ，including perimenopausal age （96.61％ vs. 99.32％，P＝0.037），the importance of perimenopausal health care knowledge （91.19％ vs. 96.95％，P＜0.001），whether the perimenopausal syndrome needs treatment （88.47％ vs. 99.32％，P＜0.001），willingness to use MHT （70.59％ vs. 94.48％ ，P＜0.001），MHT treatment timing （60.50％ vs. 95.17％ ，P＜0.001），reducing the risk of cardiovascular disease （51.68％ vs. 96.55％ ，P＜0.001），delaying aging （69.75％ vs. 97.59％ ，P＜0.001），preventing osteoporosis（65.13％ vs. 97.59％），P＜0.001）；the medical staff were higher than the non-medical staff （P＜0.05）. Totally 90％ of the students said they had gained knowledge about the prevention and treatment of common diseases ，nutrition and guidance， psychological regulation guidance hormone therapy related knowledges and exercise methods ；the proportion of the students who were willing to use MHT for 1 to 5 years（31.09％ vs. 47.93％）increased significantly. The proportion of the students who concerned about the risk of thrombosis （60.24％ vs. 36.81％），weight gain （59.64％ vs. 14.84％）and life-long dependence （52.41％ vs. 18.13％）was significantly reduced ，but that of the students who concerned about cancer risk was not diminished. From 2017 to 2020，the utilization rate of MHT was increased from 2.22％ to 62.16％ in non-medical staff among the students. CONCLUSIONS The multidisciplinary model of perimenopausal one-day outpatient service can improve the awareness of MHT among perimenopausal women ，eliminate misunderstandings ，and increase the utilization rate of MHT.

Objective:To explore the effective chemical constituents and target genes of the Sanhan-Qushi-Wenjing-Tongluo formula through the method of network pharmacology, and to further analyze the mechanism of treatoffing psoas fasciitis. Methods:The TCMSP database was used to search and screen the chemical active substances of Sanhan-Qushi-Wenjing-Tongluo formula and its target proteins acting on the human body. At the same time, the GeneCards database platform was used to predict the target of disease and the active ingredient-target network was constructed. Construct a PPI network through the STRING database, search for PPI core genes, and then perform GO enrichment analysis and KEGG enrichment analysis to find the signal pathways involved and construct a target-path network. Results:Through screening, a total of 23 key chemical components and 25 common target proteins was obtained in Sanhan-Qushi-Wenjing-Tongluo formula treating psoas fasciitis; gene analysis of enrichment analysis results include antibiotic response, cyclin-dependent proteins kinase holoenzyme complex, cytokine receptor binding, etc. Kyoto Encyclopedia of Genes and Genomes enrichment analysis results include AGE-RAGE signaling pathway, measles, endocrine resistance, inflammatory bowel disease, etc; the target genes gained which have a higher degree of matching with the above mentioned pathways include IL6, JUN, IL1B, CDK4, CCND1. Conclusion:Sanhan-Qushi-Wenjing-Tongluo formula could treat psoas fasciitis by regulating the target genes such as IL6, JUN, IL1B, CDK4 and CCND1.

Objective:To introduce a new method of root reconstruction for proximal repair of acute type A aortic dissection, and to retrospectively analyze its short-term efficacy.Methods:From January 2018 to October 2019, a total of 455 patients with acute Stanford type A aortic dissection received surgical treatment. Among them, 343 patients underwent double-jacket-wrapping(DJW) root reinforcement(11 patients underwent leaflet suspension), 81 patients underwent Bentall surgery, 15 Wheat operations, 12 untreated roots, and 4 David operations. Compared 343 patients who underwent double-jacket-wrapping root reconstruction and 81 patients who underwent Bentall surgery. The perioperative indicators and short-term survival of the two groups were compared.Results:No patients died intraoperatively. The 30-day mortality rate in the DJW group and the Bentall group were 10.5% and 7.4%, respectively( P=0.403); cardiopulmonary bypass time were(218.8±68.4) min and(240.2 ± 59.8), P=0.011; aortic clamp time were(150.6 ± 47.9) min and(181.3 ±45.6)min, P=0.000. There was no difference between the operation time and the deep hypothermia circulatory time between the two groups. The mean follow-up was(11.7±6.4) months. Seven and two follow-up deaths occurred in the DJW group and the Bentall group, respectively, and the cause of death was not related to the aortic root. The degree of aortic regurgitation after DJW was 0.7±0.5, which was significantly lower than that before surgery( P=0.000). Conclusion:Compared with Bentall surgery, DJW method is a safe and effective method for the repair of acute type A aortic dissection roots, which can obtain good perioperative and early curative effects.

Objective:To investigate the positive rates of 2019-nCoV nucleic acid in different specimens from confirmed COVID-19 cases during hospitalization and after discharge.Methods:Patients with confirmed COVID-19 were enrolled from designated hospitals. Nasal swabs, throat swabs, and specimens of stool, urine and blood were collected during hospitalization. After the patients were discharged, nasal swabs, throat swabs and stool specimens were collected during follow-up. Real-time RT-PCR was used to detect 2019-nCoV nucleic acid.Results:This study involved 25 confirmed COVID-19 cases. During hospitalization, all patients tested positive in both nasal and throat swab 2019-nCoV nucleic acid tests, and nine of them (36.00%) were positive in stool specimen test. Urine and blood specimen test results were all negative. Nasal swabs, throat swabs and stool specimens were collected from each patient 7 d and 14 d after discharge. Two patients (8.00%) tested positive for 2019-nCoV nucleic acid again in nasal and throat swab tests on 7 d, while all stool specimen tests were negative. No 2019-nCoV nucleic acid was detected in nasal swabs, throat swabs or stool samples on 14 d.Conclusions:2019-nCoV nucleic acid was detected in stool samples of confirmed COVID-19 cases during hospitalization. Nasal and throat swab nucleic acid tests turned positive again in some patients after discharge.

Objective To explore the role of radiotherapy in the treatment of primary central nervous system lymphoma. Methods Clinical data of 60 patients diagnosed with primary central nervous system lymphoma from September 2010 to December 2017 were retrospectively analyzed. Among them, 50 cases were diagnosed by histopathological examination after stereotactic biopsy or tumor resection and 10 patients were diagnosed by gadolinium enhanced magnetic resonance imaging ( MRI) . Fifty-two patients underwent chemotherapy, and 45 of them received methotrexate-based chemotherapy, 25 received rituximab-based regimen. Twenty-seven patients were given with planned whole brain radiotherapy, while 33 patients were not. Salvage radiotherapy was delivered in 9 patients after treatment failure. Results The median follow-up time was 28 months ( 5-70 months) . The median overall survival time and median progression-free survival time of the whole patients was 22 months ( 5-65 months) and 13 months ( 5-55 months) , respectively. The 4-year overall survival rate and progression-free survival rate were 61% and 33%, respectively. The 4-year overall survival rates between patients with and without planned whole brain radiotherapy were 68% and 54% ( P=0.083) . The 4-year progression-free survival rates between patients with and without planned whole brain radiotherapy were 47% and 20% ( P=0.014) , respectively. Patients with and without salvage whole brain radiotherapy had a 4-year overall survival of 49% and 68%, respectively ( P=0.398) . Among patients who received whole brain radiotherapy, patients with a lower dose of ≤36 Gy had a similar overall survival compared with those with a higher dose of>36 Gy ( 80% vs. 45%, P=0.136) . Conclusions Radiotherapy is part of the comprehensive treatment of primary central nervous system lymphoma. Planned radiotherapy may bring clinical benefits to patients during the comprehensive therapy. However, the irradiation dose to the whole brain should not be too high because of neurotoxicity.

Objective To detect the serum microRNA-148b-3p level in patients with diabetes mellitus and diabetic nephropathy,and to analyze its correlation with clinical and pathological indexes.Methods The research crowd was divided into three groups (1) diabetic nephropathy group:biopsy with diabetic nephropathy (n=25,14 males,11 females);(2) type 2 diabetes mellitus group:type 2 diabetes mellitus patients with normal urinary microalbumin/urinary creatinine value (n=10,4 males,6 females);(3) normal control group:healthy subjects (n=9,3 males and 6 females).Clinical indicators included gender,age,24-hour urine protein,systolic blood pressure (SBP),diastolic blood pressure (DBP),serum creatinine (Scr),urea (Urea),cystatin-C (Cys-C),blood albumin (ALB),urine microalbumin (UMA),triacylglycerol (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),serum uric acid (UA),fasting blood glucose (FBG),glycated hemoglobin (HbA1c),urine microalbuminuria / urinary creatinine (UACR),and estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula.Real-time quantitative PCR was applied to verify the expression of microRNA-148b-3p in serum samples of the research crowds.The relationships between microRNA-148b-3p level and clinical features was also analyzed.Results The levels of serum microRNA-148b-3p in diabetic nephropathy group and in type 2 diabetes mellitus group were 1.82 times and 1.73 times of that in normal control group (P ＜ 0.05,respectively).The level of serum microRNA-148b-3p was significantly correlated with HDL-C (r=-0.374,P=0.013),UMA (r=0.426,P=0.004),FBG (r=0.330,P=0.046) and TG (r=0.423,P=0.005).Multiple linear regression analysis showed that UMA level was independently associated with serum microRNA-148b-3p level (β=0.338,P=0.044).The area under the receiver operating characteristic curve (ROC) of serum microRNA-148b-3p in diagnosing type 2 diabetes mellitus and diabetic nephropathy was 0.835 and 0.665,respectively.Conclusions The level of serum microRNA-148b-3p of patients with type 2 diabetes mellitus or diabetic nephropathy significantly increases.The level of UMA is independently associated with serum microRNA-148b-3p level.Serum microRNA-148b-3p is expected to be a potential biomarker for the diagnosis of diabetic nephropathy.

Objective To compare the efficacy and safety of induction therapy in 3+7 protocol and 3+10 protocol in children with acute myeloid leukemia (AML). Methods Two protocols were carried out in our hospital during January 2010 to January 2015, namely 3+7 protocol(AML-06,A group) and 3+10 protocol (modified AML protocol, B group). A total of 56 cases aged from 1 year-old to 13 year-old were enrolled in A group with male to female ratio at 31:25. Five of them were classified as FAB M1, 25 as M2, 11 as M4, 10 as M5, 2 as M6 and 3 as M7. Another 44 cases aged from 1 year to 12 years were enrolled in B group with a male to female ratio at 26:18, and 17 cases were classified as FAB M2, 14 as M4, 9 as M5, 2 as M6, and 2 as M7. Efficacy and adverse events were compared between the two groups. Results The complete remission rate (CR) of B group was 70.4%, while CR in A group was 48.2%. Considering the CR, 3+10 protocol showed higher efficacy than 3+7 protocol (P< 0.05). The major adverse event was bone marrow suppression. Treatment-related mortality (TRD) in A group was 1.8%, which was lower than that in B group (2.3%). The overall survival rate in A group was 75.0%, which was lower than that in B group (86.4%, P< 0.05). Conclusions The induction therapy of 3+10 protocol and 3+7 protocol showed effectiveness for AML treatment. The 3+10 protocol showed a higher CR than 3+7 protocol with no TRD increase, indicating that the 3+10 protocol should be recommended for AML treatment in children.