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.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

Objective To analyze the relationship of miRNA-146a gene polymorphisms and ischemic post-stroke depression(PSD).Methods The SNP rs2910164 in the miRNA-146a gene in 200 ischemic PSD patients(case group)and 200 ischemic non-PSD patients(control group)was analyzed using the SNaPshot technique.The relative expression levels of miRNA-146a in the peripheral blood of two groups were determined.Results The case group showed significantly different allele and genotype frequencies of the SNP rs2910164 as compared with the control group(G vs.C:P=0.003;GG+CG vs.CC:P=0.012).Meanwhile,the case group presented a significantly lower level of miRNA-146a relative expression(P<0.05).Within the control group,additionally,the subgroup of GG+CG genotypes demonstrated a significantly lower level of miRNA-146a relative expression compared with the subgroup of CC genotypes(P<0.05).Conclusion SNP rs2910164 in the miRNA-146a is associated with the susceptibility to ischemic PSD,and G allele may play a role in the ischemic PSD.

Objective To propose a regression tree model for the estimation of blood pressure using the minimalist characteristics of photoplethysmography(PPG)signals.Methods Fifteen characteristic parameters were extracted from the PPG signals,and the 4 parameters with the highest correlations with blood pressure were screened using the Spearman correlation coefficient to construct a regression tree model for blood pressure estimation using the minimalist characteristics.Results The estimation errors of systolic and diastolic blood pressures in the constructed model were(-0.02±3.63)mmHg and(-0.04±2.10)mmHg,respectively.Conclusion The proposed regression tree model has a simple structure and high accuracy,which is of great significance for using a single-channel PPG signal for blood pressure estimation in wearable devices.

Humans ; Bradycardia/therapy* ; Tricuspid Valve Insufficiency ; Pacemaker, Artificial/adverse effects* ; Cardiac Pacing, Artificial

Objective: To observe the clinical effect of thumbtack needles combined with pediatric Tuina (Chinese therapeutic massage) for constipation in children caused by liver depression and Qi stagnation.Methods: A total of 60 children with constipation caused by liver depression and Qi stagnation were randomly divided into a combined group and a Tuina group, with 30 cases in each group. The cases in the Tuina group were treated with pediatric Tuina, while those in the combined group were treated with additional thumbtack needle therapy. We observed the clinical efficacy and the change in the number of spontaneous bowel movements per week before and after treatment. Results: After treatment, the cure rate and the total effective rate in the combined group were higher than in the Tuina group, showing statistical significance (P<0.05). Compared with the same group before treatment, the number of spontaneous bowel movements per week in both groups increased after treatment (P<0.05). With the progression of treatment, the number of spontaneous bowel movements per week increased in both groups, and the number in the combined group was more than that in the Tuina group, showing statistical significance (P<0.01). Conclusion: Thumbtack needles combined with pediatric Tuina is more effective than pediatric Tuina alone in the treatment of constipation in children caused by liver depression and Qi stagnation.

Objective:To understand the status of knowledge, attitude and practice of metabolic syndrome(MS) among the elderly in the community and analyze its influencing factors, so as to provide guidance for the prevention and treatment of MS.Methods:From January 2021 to August 2021, permanent residents(residence duration ≥6 months)aged 65 and above with regular health check examination in Fangzhuang Community Health Service Center of Fengtai District, Beijing were investigated using self-designed MS knowledge, attitude and practice questionnaire.After excluding 34 incomplete questionnaires, the 491 valid questionnaires were recycled with questionnaire valid percentage of 93.5%(491/525). The survey results were analyzed by descriptive analysis, Mann-Whitney U test, Kruskal-Wallis H test and multiple linear regression analysis and multiple linear regression.Results:The scores of MS knowledge, attitude and practice of the elderly in the community were 7(5, 10), 9(8, 10)and 19(18, 21)respectively.The correct answer rate of the diagnostic criteria of MS components was less than 50%.The score of knowledge about MS in the elderly was positively correlated with the scores of attitudes( r=0.263)and practice( r=0.134)(all P<0.01). The results of univariate and multiple linear regression analysis showed that gender, attending educational lectures and the prevalence of MS were the influencing factors of MS knowledge score(all P<0.05). Leisure time, attending educational lectures, pre-retirement occupation and regular health check examination were the influencing factors for MS attitude score(all P<0.05); attending educational lectures, leisure time, regular health check examination and pre-retirement occupation were the influencing factors for MS practice score(all P<0.05). Conclusions:The elderly in the community have a low level of knowledge about the components and diagnostic criteria of MS, but have a positive attitude and practice towards the prevention and treatment of MS.The level of knowledge, attitude and practice of MS is affected by health education lectures, occupation, regular health check examination and other factors.Health education on the diagnostic criteria and the awareness of disease prevention for the elderly in the community should be strengthened to improve the levels of the knowledge, attitude and practice of MS.

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Antineoplastic Agents/therapeutic use* ; China ; Drug Industry ; Humans ; Lung Neoplasms/drug therapy* ; Pharmaceutical Preparations

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective:To construct a core competency evaluation index system for ophthalmic specialist nurses so as to provide theoretical reference for cultivation and evaluation of ophthalmic specialized nurses in China.Methods:A research group was set up in October 2020, and the core competency evaluation index system for ophthalmic specialist nurses was initially formed by means of literature review, semi-structured interview and group discussion. From December 2020 to January 2021, an online questionnaire was used to conduct Delphi letter consultation among 23 experts in related fields nationwide, and the items were screened and modified. The weight of indicators was determined by the proportional distribution method.Results:Two rounds of consultation were conducted. The positive coefficients of experts were respectively 91.30% and 100.00%, Kendall's concordance coefficients were respectively 0.172 and 0. 192 ( P<0.05) , and the expert authority coefficient was 0.90. Finally, an index system consisting of 5 first-level indicators, 12 second-level indicators and 58 third-level indicators was formed. Conclusions:The core competence evaluation index system of ophthalmic specialist nurses constructed in this study has a high degree of enthusiasm and authority of experts, which reflects the characteristics of the ophthalmic nursing specialty and provides theoretical reference for cultivation and ability evaluation of ophthalmic specialist nurses in China.