Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To form the expert consensus on the limb management of patients with transvenous temporary cardiac pacing,standardize the limb management of patients with transvenous temporary cardiac pacing,and reduce complications related to the limb.Methods Using evidence-based methods,the evidence in this field was searched,evaluated and summarized,and relevant recommendations and research conclusions were extracted and classified by the level of evidence quality,and then the first draft of the consensus was formed.From December 2023 to January 2024,through 2 rounds of expert consultation and 4 rounds of expert meetings,the content was adjusted and the consensus was reached.Results Totally 16 experts participated in the consultation.The positive coefficient is 100%;the authoritative coefficient is 0.847 and 0.836;the average value of each index is more than＞3.8;the coefficient of variation is less than 0.21.The Kendall's harmony coefficient of the 2 rounds of expert consultation is 0.372 and 0.314,respectively,which were statistically significant.The consensus covers the preoperative,intraoperative and postoperative on limb management of patients with transvenous temporary cardiac pacing.Totally 11 themes were involved,including the preoperative preparation,position and catheter fixation in operation,position and catheter fixation in postoperative,activity,turn and transfer,duty shift on limb,nursing care after withdrawal of the catheter,prevention of deep vein thrombosis of the operative limb and prevent infection.Conclusion The consensus is highly scientific,and it is helpful to standardize the limb management of patients with transvenous temporary cardiac pacing.

Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

Objective To find a reliable, simple, and easily-operated method for the screening of neonatal congenital heart disease (CHD). Methods A total of 7 105 neonates born from January 2017 to July 2017 were selected. The validity and reliability of physical examination, pulse oximetry screening (POS), and perfusion index (PI) in the screening of neonatal CHD were evaluated according to the diagnosis made by color Doppler echocardiography. Results When physical examination, POS or PI was used separately in screening for CHD, the sensitivities were in the range of 13.11%~73.77%, specificities 50.20%~99.34%, Youden indexes 0.12~0.70, the total coincidence rates 50.40%~98.86%, positive predictive values 1.27%~40.70%, and negative predictive values 99.29%~99.70%. When physical examination, POS and PI were combined (two or three indexes were positive) for screening, the sensitivities and Youden indexes were 85.25% and 0.82 respectively, which were higher than those of single indicators and suggested that the combination had higher authenticities. The total coincidence rate of the combination was 97.07%, and, although it was lower than POS group (98.86%) and PI screening group (98.58%), it still had a good reliability. Conclusions The combination of physical examination, POS and PI has a certain clinical value in neonatal CHD screening.

Objective To investigate the clinical efficacy of fire needling plus medication in treating cystic acne.Methods Fifty-eight patients with cystic acne were randomly allocated to treatment and control groups, 29 cases each. The treatment group received fire needling plus oral administration of isotretinoin and the control group, oral administration of isotretinoin alone. The number of cysts was observed in the two groups and the clinical therapeutic effects were compared between the two groups. Results There was a statistically significant difference in the number of cysts between before treatment and at one, two, three or four weeks after in the two groups (P<0.01,P<0.05). The total efficacy rate was 89.3% in the treatment group and 34.5% in the control group; there was a statistically significant difference between the two groups (P<0.01).Conclusion Fire needling plus medication is an effective way to treat cystic acne.

Objective To determine whether erythromycin-resistant propionibacteria isolated from patients with acne in Wuhan city harbor 23S rRNA gene mutations as well as the transposon Tn5432 carrying ermX genes.Methods Twenty-nine Propionibacterium strains isolated from outpatients with acne in Wuhan city were included in this study.The E-test method was used to determine the susceptibility of these strains to erythromycin and clindamycin.PCR was performed to amplify the 23S rRNA,ermX,ermX (cj),IS1249a and IS1249b genes from resistant strains followed by DNA sequencing and nucleotide alignment.Results Among the 29 Propionibacterium strains,19 were identified as P.acnes and 10 as P.avidum.All of these Propionibacterium strains were resistant to erythromycin (MIC ＞ 256 μg/ml) and clindamycin (MIC ＞ 256 μg/ml),except for 3 P.acnes strains sensitive to clindamycin.Seven P.acnes strains resistant to both antibiotics exhibited an A→G transition at a position cognate with Escherichia coli 23S rRNA 2058.An A→G transition at a position cognate with E.coli 23S rRNA 2059 was identified in one clindamycin-resitant and three clindamycin-sensitive P.acnes isolates.The ermX gene was found in the remaining 8 P.acnes isolates and 2 P.avidum isolates,with the sequence 100％ identical to the reference sequence of the ermX gene of P.acnes in Genbank.Meanwhile,the ermX (cj) gene was successfully amplified from the other 8 P.avidum isolates,which showed 99％ sequence homology with the ermX (cj) gene of Corynebacterium jeikeium,but 94％ homology with the ermX gene of P.acnes in Genbank.Both IS1249a and IS1249b genes were amplified in the 10 ermX gene-positive Propionibacterium strains,but not in the other ermX gene-negative strains.Conclusions The erythromycin resistance in Propionibacterium isolates from Wuhan city may be associated with the A→G transition at the E.coli equivalent bases 2058 and 2059 of the 23S rRNA gene,as well as the presence of the erm X (transferred through the transposon Tn5432) and ermX (c j) genes.

Biochemical analysis assays based on colorimetric methods using gold nanoparticles have many advantages including high sensitivity, good selectivity, naked-eyes readout and complex instruments free. These methods have good prospects in applications. The biomolecule assay is highly relative with human health. This review mainly focuses on colorimetric assays applying gold nanoparticles for biomolecules detection.

Objective:To determine the location of mycobacterium tuberculosis(MTB) and whether the cellular immunity is induced after intragastric administration of BCG in mice.Methods:Viable MTB were detected in mesenteric lymph nodes?spleen and lungs at day 15,30 and 60 after intragastric administration of BCG to mice.The proliferation of T-lymphocyte with the stimulus of the purified protein derivative(PPD) was measured at day 60 and 90 after intragastric administration of BCG to mice.The expression of interleukin-2(IL-2) of T-lymphocyte in spleen was detected at day 60 and 90 after intragastric administration of BCG.Results:Viable MTB were detected in the mesenteric lymph nodes and spleen at day 15,30 and 60 after intragastric administration.At day 60 and 90 after intragastric administration of BCG to mice,the ratio of T-lymphocyte proliferation was 31.32%,37.94% separately and the production of IL-2 was 37.47?5.60 U/ml,39.41?7.73 U/ml separately.There were no statistically significant differences in the cellular immunity between the mice of the intragastric administration of BCG significant differences in the cellular immunity between the mice of the intragastric administration and the mice of the subcutaneous vaccination of BCG( P 0.05).Conclusion:Intragastric administration of BCG can induce cellular immunity in mice.