HR-positive HER2-low breast cancer is a new hotspot therapeutic subtype, accounting for approximately 53.7% of all breast cancers. Patients with this type of cancer tend to have a high rate of lymph node metastasis and poor sensitivity to neoadjuvant chemotherapy and conventional anti-HER2 therapy, and exploring therapeutic strategies for this subtype of patient is a current clinical challenge. Therapeutic strategies for HR-positive HER2-low breast cancer are constantly being updated, including CDK4/6 inhibitors across the lines of therapy, and next-generation antibody-drug conjugates such as T-DXd. With the accumulation of high-level evidence-based evidence for HR-positive HER2-low breast cancer in the future, the research data will provide more practical support for precise diagnosis and treatment, thereby improving the prognosis of patients with HR-positive HER2-low breast cancer.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Machine Learning ; Image Processing, Computer-Assisted/methods*

Objective To apply a phantom for dose measurement in interventional therapy for pediatric vascular diseases, and calculate the effective dose (E) and conversion coefficient of dose area product (DAP) to E, and to provide a dose reference for studying radiation dose and radiation protection in children. Methods Thermoluminescent dosimeters were placed in the organs of the phantom. Low-, medium-, and high-dose groups were set for three types of vascular anomalies based on the duration of fluoroscopy. Digital subtraction angiography was used to simulate exposure conditions at different dose levels. The organ dose was measured, and the effective dose was calculated. Results For the three groups of vascular anomalies in the head and face, the red bone marrow doses were 8.15, 30.34, and 43.53 mGy, respectively, the effective doses were 12.88, 47.84, and 73.12 mSv, respectively; and the average conversion coefficient of DAP to E was 2.16. For the three groups of vascular anomalies in the trunk, the red bone marrow doses were 2.11, 15.62, and 31.21 mGy, respectively; the effective doses were 12.39, 70.56, and 134.60 mSv, respectively, and the average conversion coefficient of DAP to E was 3.03. For the three groups of vascular anomalies in the lower extremities, the red bone marrow doses were 3.58, 6.50, and 12.28 mGy, respectively, the effective doses were 3.64, 7.04, and 14.85 mSv, respectively, and the average conversion coefficient of DAP to E was 0.73. Conclusion Patient dose and DAP-to-E conversion coefficient are in the following order: vascular anomalies in the trunk > vascular anomalies in the head and face > vascular anomalies in the lower extremities. The dose data obtained can be used to estimate children’s radiation exposure.

Objective:To investigate factors associated with the concentration of hydroxychloroquine (HCQ) and its metabolites in peripheral blood of patients with systemic lupus erythematosus (SLE) who were receiving long-term oral HCQ treatment.Methods:SLE patients who had been taking HCQ for more than 3 months were recruited. Clinical characteristics, laboratory test results and SLE disease activity index (SLEDAI) scores were examined. The concentrations of HCQ and its metabolites from peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Student's-test and Nonpara-metric tests were used to compare quantitative data, Chi-square and Fisher's exact tests were used to analyze qualitative data. Correlation between the test results was assessed by correlation coefficient. Variables with P values less than 0.05 in univariate analysis were entered into a logistic regression model. Results:In total, 191 SLE patients on long-term HCQ treatment were included in the analysis. Medians of HCQ blood concentrations ([HCQ]), desethylhydroxychloroquine (DHCQ) blood concentrations ([DHCQ]), desethylchloroquine (DCQ) blood concentrations ([DCQ]) and bisdesethylchloroquine (BDCQ) blood concentrations ([BDCQ]) were 523.19 (402.63, 677.88) ng/ml, 291.79 (212.30, 432.51) ng/ml, 49.37 (35.00, 73.05) ng/ml, 21.78(14.37, 52.46) ng/ml respectively. On multivariate analysis, weight-adjusted oral HCQ dose [ OR(95% CI)=1.366 (1.053, 1.772) , P=0.019], the course of hydroxychloroquine [ OR (95% CI) =0.991 (0.984, 0.999), P=0.026], estimated glomerular filtration rate [ OR(95% CI)=0.984 (0.971, 0.997), P=0.014] and platelet count [ OR (95% CI)=1.010 (1.005, 1.015), P<0.001] were associated with [HCQ]. [HCQ], [DCQ], [BDCQ], [BDCQ]/[HCQ] were negatively correlated with estimated glomerular filtration rate (eGFR) ( r=-0.20, P=0.006; r=-0.19, P=0.010; r=-0.26, P<0.001; r=-0.15, P=0.044, respectively) after adjusted for age, course of disease, duration of HCQ treatment and weight adjusted HCQ dosage, [DHCQ]/[HCQ] was negatively correlated with the SLEDAI score ( r=-0.16, P=0.027) when the effects of glucocorticoid was controlled, [BDCQ]/[HCQ] among different renal function levels was statistically significant ( H=12.46, P=0.014). Conclusion:The factors associated with HCQ blood concentrations in SLE patients on long-term oral HCQ treatment are weight-adjusted HCQ dosage, duration of hydroxychloroquine intake and renal function. In addition, [BDCQ] is closely correlated with renal function, [DHCQ] is correlated with SLE disease activity.

Objective:To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV).Methods:Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3).Results:Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA:30.2±11.5 vs. 1.9±0.6, P<0.001;MPO:(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, P=0.01; C5a:(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, P<0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, P<0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels ( r=0.537, P=0.001 and r=0.358, P=0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level ( β=0.695, P=0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels ( r=-0.335, P=0.046; r=-0.372, P=0.026; r=-0.577, P<0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level ( β=-0.374, P=0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a ( r=0.598, P<0.001; r=0.599, P<0.001; r=0.537, P=0.001; r=0.415, P=0.012; respectively) and negatively correlated with MPO level in neutrophils ( r=-0.342, P=0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils ( β=0.511, P=0.002). Conclusion:In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.

Objective:To compare the efficacy and safety between microvascular anastomostive device (MAD) and hand-sewn (HS) in free flap reconstruction.Methods:Databases in Pubmed, Embase, CNKI, Wanfang, CBM and Weipu etc. The comparative study of MAD device and manual suture in free flap repair of soft tissue defects published in domestic and foreign official journals from January, 1950 to October, 2019 was collected. The quality of the included studies was strictly evaluated and relevant data were extracted. Revman 5.3 software was used to analyze all relevant data.Results:Fifteen trials with 5 539 patients were included. There was significant difference between MAD and HS in time of venous anastomoses ( SMD=-5.46, 95% CI: -7.50, -3.41, P<0.001), time of artery anastomoses ( SMD=-5.16, 95% CI: -9.61, -0.71, P=0.02), vascular crisis ( RR=0.49, 95% CI: 0.34, 0.70, P<0.001) and flap necrosis ( RR=0.52, 95% CI: 0.32, 0.86, P=0.01), the difference between the 2 groups was statistically significant ( P< 0.05). Conclusion:According to the analyses of the pooled results of MAD group and HS group, the data tend to suggest that MAD is superior to HS in the reconstruction with free flap.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective To investigate the risk factors of posttransplantation initial diabetes mellitus(PTDM) and the prognostic impact on living donor renal transplantation recipients.Methods The clinical data of 273 living donor renal transplantation recipients from 2007 to 2013 were retrospectively studied.Recipients were divided into PTDM group and non-PTDM group according to the diagnostic standard.Potential risk factors were analyzed by logistic regression model.The incidence of adverse events were analyzed and compared between the two groups.Recipients and grafts survival (overall and death-censored) rate was analyzed by Kaplan-Meier method.Results During the 5-year follow-up period,62 out of total 273 relative-living recipients were diagnosed as PTDM (22.71％).Six risk factors for PTDM were identified:BMI ≥25 kg/m2 (OR,3.911;95％CI,1.811-8.445),male gender (OR,2.291;95％CI,1.184-4.436),family history of diabetes (OR,3.225;95％CI,1.447-7.186),ARE (OR,4.481;95％CI,1.908-10.522),administration of tacrolimus (OR,3.678;95％CI,1.807-7.483) and impaired fasting glucose (IFG) diagnosed at 1st week posttransplantation (OR,3.925;95 ％ CI,1.997-7.716).The infection rate was significantly higher in PTDM group than in non-PTDM (16.12％ vs.7.11 ％,P =0.045).No significant difference was observed in both patient and graft survival (both overall and death-censored graft survival) rate during the 5-year follow-up period.Conclusion PTDM was associated with multiple risk factors,including male,high BMI,IFG during 1st week after transplantation,ARE,tacrolimus administration and family diabetes history.PTDM increased the infection incidence but did not affect both recipient and allograft survival significantly during the 5-year follow-up period.

Objective:To investigate the value of amino acid metabolomics in evaluating chemotherapeutic response of patients with ad-vanced breast cancer, the changes in the levels of 32 amino acids in the circulating serum of patients before (baseline) and after the first cycle (prognosis) of chemotherapy were tested. Methods:Seventy-three advanced breast cancer patients with local recurrence and distant metastasis admitted at the Liaoning Cancer Hospital from March 2015 to October 2016 were enrolled. Peripheral blood samples (2 mL) were collected before and after the first cycles of chemotherapy from each patient. Thirty-two amino acids in the se-rum were tested using the ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients were catego-rized into the improvement or deterioration groups, based on the first imaging test after 2-4 cycles of chemotherapy. The changes in amino acids levels were analyzed in different prognosis groups. Results:The levels of the 32 amino acids ranged 3-180000 pmol/L. Compared to their baseline levels, both glycine and L-glutamine increased in the improvement group, but decreased in the deteriora-tion group. Sarcosine was significantly reduced in the improvement group, while differences in its levels were not obvious in the deteri-oration group. L-threonine, taurine, iminodiacetic acid, and L-glutamic acid were increased in both groups. Conclusion:Changes in the serum levels of glycine, sarcosine, and the other amino acids before and after the first cycles of chemotherapy can predict chemothera-peutic response in patients with advanced breast cancer. Amino acid metabolomics may become a potential biomarker for predicting the efficacy of chemotherapy earlier than that of imaging tests, and thereby help improve therapeutic strategies for advanced breast cancer.