Objective:To discuss the oncologic safety, aesthetic outcome, and upper extremity function of single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) in the treatment of early breast cancer.Methods:From January 2014 to August 2019, a total of 80 patients with stage Ⅰ and Ⅱ breast cancer underwent SIE-NSM, at Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. Estimated the oncologic safety, aesthetic outcome, and upper extremity function.Results:SIE-NSM was performed successfully on all 80 patients.There was no serious complication after surgery.The follow-up time was 16-82 months and the median follow-up time was 42 months. Local recurrence occurred in two patients, and there was no distant metastases. Four (5%) patients developed grade 1-3 nipple-areola complex ischemia. There were no cases of subcutaneous effusion.The satisfaction with breasts, chest well-being, psychosocial well-being, and sexual well-being scores were confirmed to be highly rated by Breast-Q scale. Upper extremity function score confirmed that good upper limb function was preserved after surgery. The mean length of incision was (3.6±0.8) cm, and the blood loss was (24.7±19.3) mL.Conclusions:SIE-NSM can achieve a higher cosmetic score and a better recovery of upper limb function on the premise of ensuring the safety of the tumor.This novel method is an appropriate surgical option for patients with early breast cancer.

Objective:To examine the clinical application value of single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer.Methods:From February 2014 to July 2019, the clinic-pathological data of 34 early breast cancer patients received single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation at Department of General Surgery, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. All the patients were female, with an age of 46(11) years ( M( Q R)) (range: 26 to 64 years). The radical cure degree of operation, cosmetic effect after operation were evaluated. The satisfaction to operation and personal quality of life after operation was accessed by BREAST-Q scale. Results:All surgical procedures were successfully completed. The operation time was (313.4±11.7) minutes (range: 200 to 485 minutes). The blooding-liquid was (33.8±3.3) ml (range: 10 to 100 ml). There were 5 cases (14.7%) of nipple areola necrosis after operation, of which 1 patient received taking the prosthesis out because of prosthesis exposure. There was no capsular contracture or postoperative bleeding case. The follow-up time was 35(17) months (range: 12 to 77 months), and there was one case suffering local recurrence and metastasis, and another suffering metastasis. The scores of postoperative breast satisfaction, psychosocial status, chest wall status and sexual health were 78.32±2.57 (range: 55 to 100), 89.12±2.30 (range: 82 to 100), 91.47±1.33 (range: 43 to 100), and 78.50±2.68 (range: 39 to 100).Conclusion:Single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer can achieve provided curative and cosmetic effect on patients with breast cancer, with good patients′ postoperative quality of life and satisfaction.

Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

Objective:To examine the clinical application value of single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer.Methods:From February 2014 to July 2019, the clinic-pathological data of 34 early breast cancer patients received single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation at Department of General Surgery, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. All the patients were female, with an age of 46(11) years ( M( Q R)) (range: 26 to 64 years). The radical cure degree of operation, cosmetic effect after operation were evaluated. The satisfaction to operation and personal quality of life after operation was accessed by BREAST-Q scale. Results:All surgical procedures were successfully completed. The operation time was (313.4±11.7) minutes (range: 200 to 485 minutes). The blooding-liquid was (33.8±3.3) ml (range: 10 to 100 ml). There were 5 cases (14.7%) of nipple areola necrosis after operation, of which 1 patient received taking the prosthesis out because of prosthesis exposure. There was no capsular contracture or postoperative bleeding case. The follow-up time was 35(17) months (range: 12 to 77 months), and there was one case suffering local recurrence and metastasis, and another suffering metastasis. The scores of postoperative breast satisfaction, psychosocial status, chest wall status and sexual health were 78.32±2.57 (range: 55 to 100), 89.12±2.30 (range: 82 to 100), 91.47±1.33 (range: 43 to 100), and 78.50±2.68 (range: 39 to 100).Conclusion:Single-port inflatable endoscopic nipple sparing mastectomy with immediate reconstruction using prosthesis implantation in the treatment of early breast cancer can achieve provided curative and cosmetic effect on patients with breast cancer, with good patients′ postoperative quality of life and satisfaction.

Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.

Objective To analyze results of breast cancer screenings in the Cancer Screening Program in Urban China (CanSPUC) during 2012-2013. Methods In 14 cities of 9 provinces (Eastern Region: Beijing, Hebei, Liaoning, Shandong and Guangdong; Central Region: Heilongjiang and Hunan;Western Region: Chongqing and Gansu), 198 097 women aged 40-69 years who had lived in their cities for ≥3 years were surveyed through a cancer risk assessment questionnaire during 2012-2013. The questionnaires identified women considered to be at high risk for breast cancer, of whom 17 104 received screening examinations, for whom complete records of breast cancer screening and other data were available for 12 440 subjects altogether, including breast ultrasound exams for subjects 40-44 years old. Subjects older than 45 years or in whom breast imaging reporting and data system (BI-RADS) ultrasound had found≥3 lesions also underwent mammography. In this cohort, BI-RADS 3 class was defined as suspicious and BI-RADS ≥4 class as positive. Chi-square tests were used to compare breast cancer screening results by groups. Results As of October 2013, breast cancer screening percentages for the 12 440 subjects for whom full data were available were, by region, Eastern: 55.43% (6 895); Central: 21.45% (2 669); and Western:23.12% (2 876); by age, 40-44 years: 5.50% (684); ≥45 years: 94.50% (11 756). Using BI-RADS, 2018 subjects were found to have 3 lesions (detection rate:16.22%), which were distributed regionally as Eastern:19.00% (1 310 women), Central: 13.75% (367) and Western; 11.86% (341); χ2=91.45, P<0.001; and 289 were found to have≥4 lesions (detection rate:2.32%), which were distributed regionally as Eastern:2.41%(166), Central:1.54%(41) and Western;2.85%(82);χ2=11.04, P=0.004. Women aged 50-54 years had the highest detection rate of BI-RADS 3 lesions at 18.74% (561/2 994), and those aged 40-44 years had the highest detection rate of BI-RADS ≥4 at 2.92% (20/684). Conclusion Detection rates of BI-RADS ≥4 lesions were highest in the Western region and in women aged 40-44 years, and lowest in the Central region and in women aged 60-64 years. Detection rates of BI-RADS 3 lesions were highest in the Eastern region and in women aged 50-54 years and the lowest in the Western region and in women aged 60-64 years.

Objective:The research was aimed to investigate the association between serum total homocysteine (tHcy) and subacute combined degeneration of the spinal cord (SCD).Methods:A retrospective survey of 106 newly diagnosed patients with SCD were enrolled in this research who were treated in the department of neurology of Xijing Hospital from January 2008 to February 2019, meanwhile, 121 patients with spinal cord lesion (not SCD) and 104 neurology mild outpatients were selected as controls. Serum tHcy level was determined by using the chemiluminescent immunoassay assay. A multivariate logistic regression model was used to analyze the risk factors for SCD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and Youden index were used to evaluate the diagnostic efficacy of tHcy. Spearman correlation analysis was used to observe the correlation between tHcy and SCD severity. The SCD patients were categorized into normal or mild tHcy group, moderate tHcy group, and severe tHcy group based on tHcy levels. Clinical symptoms, nerve conduction velocity, magnetic resonance imaging (MRI) findings from the patients were studied.Results:The serum tHcy levels in SCD patients were 64.3(26.5, 98.8) μmol/L, while in patients with spinal cord lesion (not SCD) group were 13.7(10.8, 19.2) μmol/L, neurology mild outpatients were 10.6(8.2, 13.0) μmol/L, which was higher in SCD group ( H=112.020, P<0.001), ( H=165.525, P<0.001).The multivariate logistic regression model showed tHcy is the impact factor of SCD ( OR=1.107, 95% CI:1.077-1.139, P<0.001). At ROC analysis, tHcy showed diagnostic value with an optimal cut-off value of 24.9 μmol/L (AUC 0.913, 95% CI: 0.875-0.951, sensitivity 79.2%, specificity 91.6%). Spearman correlation analysis showed that tHcy was positively correlated with functional disability rating scale ( r=0.254, P=0.009). Conclusions:Serum tHcy is the risk factor for SCD and related to its disability. Focus on the increased level of tHcy plays a positive role in the diagnosis of SCD.

Objective:The research was aimed to investigate the association between serum total homocysteine (tHcy) and subacute combined degeneration of the spinal cord (SCD).Methods:A retrospective survey of 106 newly diagnosed patients with SCD were enrolled in this research who were treated in the department of neurology of Xijing Hospital from January 2008 to February 2019, meanwhile, 121 patients with spinal cord lesion (not SCD) and 104 neurology mild outpatients were selected as controls. Serum tHcy level was determined by using the chemiluminescent immunoassay assay. A multivariate logistic regression model was used to analyze the risk factors for SCD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and Youden index were used to evaluate the diagnostic efficacy of tHcy. Spearman correlation analysis was used to observe the correlation between tHcy and SCD severity. The SCD patients were categorized into normal or mild tHcy group, moderate tHcy group, and severe tHcy group based on tHcy levels. Clinical symptoms, nerve conduction velocity, magnetic resonance imaging (MRI) findings from the patients were studied.Results:The serum tHcy levels in SCD patients were 64.3(26.5, 98.8) μmol/L, while in patients with spinal cord lesion (not SCD) group were 13.7(10.8, 19.2) μmol/L, neurology mild outpatients were 10.6(8.2, 13.0) μmol/L, which was higher in SCD group ( H=112.020, P<0.001), ( H=165.525, P<0.001).The multivariate logistic regression model showed tHcy is the impact factor of SCD ( OR=1.107, 95% CI:1.077-1.139, P<0.001). At ROC analysis, tHcy showed diagnostic value with an optimal cut-off value of 24.9 μmol/L (AUC 0.913, 95% CI: 0.875-0.951, sensitivity 79.2%, specificity 91.6%). Spearman correlation analysis showed that tHcy was positively correlated with functional disability rating scale ( r=0.254, P=0.009). Conclusions:Serum tHcy is the risk factor for SCD and related to its disability. Focus on the increased level of tHcy plays a positive role in the diagnosis of SCD.

Objective To analyze results of breast cancer screenings in the Cancer Screening Program in Urban China (CanSPUC) during 2012-2013. Methods In 14 cities of 9 provinces (Eastern Region: Beijing, Hebei, Liaoning, Shandong and Guangdong; Central Region: Heilongjiang and Hunan;Western Region: Chongqing and Gansu), 198 097 women aged 40-69 years who had lived in their cities for ≥3 years were surveyed through a cancer risk assessment questionnaire during 2012-2013. The questionnaires identified women considered to be at high risk for breast cancer, of whom 17 104 received screening examinations, for whom complete records of breast cancer screening and other data were available for 12 440 subjects altogether, including breast ultrasound exams for subjects 40-44 years old. Subjects older than 45 years or in whom breast imaging reporting and data system (BI-RADS) ultrasound had found≥3 lesions also underwent mammography. In this cohort, BI-RADS 3 class was defined as suspicious and BI-RADS ≥4 class as positive. Chi-square tests were used to compare breast cancer screening results by groups. Results As of October 2013, breast cancer screening percentages for the 12 440 subjects for whom full data were available were, by region, Eastern: 55.43% (6 895); Central: 21.45% (2 669); and Western:23.12% (2 876); by age, 40-44 years: 5.50% (684); ≥45 years: 94.50% (11 756). Using BI-RADS, 2018 subjects were found to have 3 lesions (detection rate:16.22%), which were distributed regionally as Eastern:19.00% (1 310 women), Central: 13.75% (367) and Western; 11.86% (341); χ2=91.45, P<0.001; and 289 were found to have≥4 lesions (detection rate:2.32%), which were distributed regionally as Eastern:2.41%(166), Central:1.54%(41) and Western;2.85%(82);χ2=11.04, P=0.004. Women aged 50-54 years had the highest detection rate of BI-RADS 3 lesions at 18.74% (561/2 994), and those aged 40-44 years had the highest detection rate of BI-RADS ≥4 at 2.92% (20/684). Conclusion Detection rates of BI-RADS ≥4 lesions were highest in the Western region and in women aged 40-44 years, and lowest in the Central region and in women aged 60-64 years. Detection rates of BI-RADS 3 lesions were highest in the Eastern region and in women aged 50-54 years and the lowest in the Western region and in women aged 60-64 years.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.