[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Objective:To investigate the efficacy of postmastectomy radiotherapy (PMRT) for human epidermal growth factor receptor 2 (HER2)-positive T 1-2N 1M 0 breast cancer in the context of HER2-targeted therapy. Methods:This study collected the clinical data of 105 female patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy in the First Affiliated Hospital of Bengbu Medical College from January 2013 to December 2019. Then, the clinical outcomes of these patients were observed, and the prognostic factors and the efficacy of PMRT were analyzed. Results:The median follow-up time was 50 months (ranging from 14 to 107 months), and the 5-year overall survival (OS), local-regional recurrence-free survival(LRFS), and disease-free survival (DFS) were 81.6%, 91.9%, and 76.2%, respectively. The multivariate analysis indicated that independent prognostic factors for OS and DFS include the age, pathologic grade, and tumor size; the independent risk factors for LRFS include positive lymph node ratio (LNR) and hormone receptor (HR) status; and the independent prognostic factor for DFS was PMRT (HR: 2.85, 95% CI: 1.10-8.80, P < 0.05). The subgroup analysis suggested that PMRT significantly improved the OS of various high-risk subgroups ( χ2=4.01-9.18, P < 0.05). However, the further stratified analysis indicated that PMRT only increased the OS of the patients who did not receive HER2-targeted therapy in various high-risk subgroups ( χ2=4.50-6.70, P < 0.05), while there was no statistical difference before and after PMRT for the individuals who received targeted treatment ( P > 0.05). Conclusions:PMRT is an independent prognostic factor for the DFS of patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy. PMRT can improve the OS of high-risk patients with ages < 45 years old, pathologic grade Ⅲ, tumor diameter ≥ 3 cm, LNR > 10%, and HR (-) who received no HER2-targeted therapy. However, the efficacy may be compromised to some extent in the context of the application of HER2-targeted therapy.

Objective:To explore the effects of the deep inspiration breath-hold (DIBH) technique on cardiac dosimetry in internal mammary node irradiation with intensity-modulated radiation therapy (IMN-IMRT) for postoperative left breast cancer.Methods:Totally 23 left breast cancer patients in the First Affiliated Hospital of Bengbu Medical College from Octorber 2021 to July 2022 receiving postoperative IMN-IMRT were enrolled in this study. The changes in dosimetric parameters for their heart and left anterior descending coronary artery (LAD) in the DIBH mode were observed, and the potential factors affecting DIBH effects were analyzed.Results:Compared with the free breath (FB) mode, the DIBH mode manifested a heart volume decrease by 18% ( t = 10.47, P < 0.001), a left lung volume increase by 42% ( t = -14.55, P < 0.001), and significantly reduced dosimetric parameters ( Dmean, Dmax, V5- V30) for the heart and LAD, exhibiting statistically significant differences ( t=-13.38 to -3.30, P<0.05). As indicated by the Pearson correlation analysis, the relative ratio of cardiac dose reduction was positively correlated with that of left lung expansion ( r = 0.82, P < 0.001) and negatively correlated with the patient′age ( r = -0.56, P = 0.005). Conclusions:DIBH can effectively reduce the heart and LAD radiation doses in IMN-IMRT for postoperative left breast cancer and that the patient's age, and the DIBH effects might be affected by the vital capacity.

Objective:To investigate the effects of fluoride exposure on proliferation, apoptosis and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in mice.Methods:BMSCs were isolated and cultured from femur bone marrow of C57BL/6 mice (6 - 8 weeks). The cells in passage 3 were used to detect the surface markers of stem cells by flow cytometry. The cells were cultured in media with a final fluoride concentration of 0.0, 0.1, 1.0, 5.0, 10.0, 15.0, 20.0 and 40.0 mg/L, respectively. The effects of different fluoride concentrations on BMSCs cell proliferation (CCK8 method), apoptosis (flow cytometry analysis), osteogenic differentiation ability [alizarin red and alkaline phosphatase (ALP) staining] were detected. Western blot was applied to detect the levels of apoptosis-related proteins [poly ADP-ribose polymerase (PARP)], mitogen-activated protein kinase (MAPK) pathway member proteins [extracellular regulated protein kinase 1/2 (ERK1/2), c-Jun amino-terminal kinase (JNK), p38 and phosphorylated ERK, JNK, p38 (p-ERK, p-JNK, p-p38)], osteogenic differentiation-related protein [Runt-related transcription factor 2 (Runx2), ALP] and Wnt/β-catenin pathway member proteins [glycogen synthase kinase-3β (GSK3β), phosphorylated GSK3β (p-GSK3β) and β-catenin]. Immunocytofluorescense staining was applied to evaluate the expression levels of p-GSK3β and β-catenin. The two pathways (MAPK and Wnt/β-catenin) were blocked by SP600125 and DKK-1, respectively, to testify their involvement in mechanisms of apoptosis and osteogenic differentiation.Results:The mouse BMSCs were successfully isolated and cultured. Flow cytometry analysis showed that the mesenchymal stem cell surface biomarkers (CD73, CD90 and CD105) were positively expressed. The comparison of cell proliferation at three time points (24, 48 and 72 h) in each concentration group was statistically significant ( F = 65.36, 160.04 and 365.32, P < 0.001), and the comparison of early apoptosis (24 h) in each concentration group was statistically significant ( F = 214.04, P < 0.001); compared with the 0.0 mg/L group, the cell proliferation in 15.0, 20.0 and 40.0 mg/L groups decreased, and the early apoptosis rate in 10.0, 15.0 and 20.0 mg/L groups increased ( P < 0.05). When cells were treated with 15.0 mg/L fluoride for 0 - 24 h, the p-JNK/JNK ratio was higher at 2, 4, 8, 12, 18 and 24 h compared with that at 0 min ( P < 0.05); compared with the fluoride group (15.0 mg/L), the early apoptosis rate of cells after SP600125 block decreased ( P < 0.05), and the protein expression levels of PARP and p-JNK decreased ( P < 0.05). After osteogenic induction, compared with the 0.0 mg/L group, in 0.1 and 1.0 mg/L groups ALP staining was enhanced and the number of calcified nodules increased, and the protein expression levels of Runx2 and ALP in the 0.1 and 1.0 mg/L groups were higher ( P < 0.05). After osteogenic induction, compared with the 0.0 mg/L group, the p-GSK3β/GSK3β ratio and β-catenin protein level were significantly higher in the 0.1 and 1.0 mg/L groups ( P < 0.05); and compared with the fluoride group (1.0 mg/L), addition of DKK-1 significantly decreased the protein expression levels of p-GSK3β and β-catenin and reduced the nuclear entry of β-catenin, and ALP staining decreased and the number of calcified nodules decreased. Conclusions:High concentration of fluoride (> 10.0 mg/L) inhibits the proliferation and promotes apoptosis of BMSCs, while low concentration of fluoride (0.1, 1.0 mg/L) promotes osteogenic differentiation. The MAPK/JNK pathway and the classical Wnt pathway are involved in the above cellular processes, respectively.

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

[Abstract] Objective: To investigate the lung cancer-associated driver gene mutations in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) in Yunnan area, and to explore their association with clinical pathological features. Methods: Peripheral blood of 304 patients with stage Ⅳ NSCLC were collected from Molecular Diagnostic Center of Yunnan Cancer Hospital during January 2019 to December 2019. Next generation sequencing (NGS) technique was used to detect the mutation of NSCLC related driver genes, chi-square test was used to analyze the relationship between the major mutant genes and the clinicopathological features of patients, and Logistic regression was used to analyze the independent risk factors. Results: In the peripheral blood of 304 patients with stage Ⅳ NSCLC, there were 120 (39.47%) cases with EGFR mutations, 12 (3.95%) cases with ALK fusion, 36 (11.84%) case with other mutations such as KRAS, BRAF and RET. The main EGFR mutations were 19del and L858R (69.17%). The mutation rate of EGFR was higher in female, young, non-smoking, non-chemotherapy and lung adenocarcinoma patients (49.26% vs 31.55%, 45.39% vs 33.56%, 45.92% vs 27.78%, 45.07% vs 26.37%, 42.39% vs 10.71%, all P<0.05). Multivariate analysis showed that female, no history of chemotherapy and lung adenocarcinoma were independent risk factors for EGFR mutations (all P<0.05). Conclusion: Using NGS technology to detect the driver genes in peripheral blood of patients with advanced NSCLC in Yunnan area showed that the mutation rate of EGFR was higher in women and lung adenocarcinoma patients without chemotherapy history.

BACKGROUND: Lung cancer is the most common neoplasmas with a poor prognosis and a low 5-year survival rate. Early screening is an important measure for the prevention and treatment of lung cancer. At present, different countries have issued corresponding lung cancer screening guidelines, but China still lacks guidelines based on Chinese population research. Therefore, the National Cancer Center launched a Multi-center Cancer Screening Program in Urban China. This study analyzed the evaluation of lung cancer risk assessment model and screening effect in urban China of Yunnan, so as to explore the evaluation model of high-risk lung cancer population suitable for China's national conditions and develop lung cancer screening guidelines for Chinese. METHODS: A questionnaire survey and lung cancer risk assessment were conducted on 165,337 people in 36 street offices in 4 main urban areas of Kunming, Yunnan Province, using cluster sampling method from January 2015 to December 2019. People with high-risk of lung cancer conducted low-dose computed tomography (LDCT) screening of chest. What's more, all participants were followed up by active or passive follow-up. RESULTS: There were 264 patients were diagnosed lung cancer by pathology, and the overall incidence of lung cancer was 0.16% (264/165,337). The high-risk group (0.31%, 116/37,914) was higher than the non-high-risk group (0.12%, 148/127,423), and the difference was statistically significant (P<0.001). The incidence of lung cancer in the high-risk group was higher than the non-high-risk group among the male, female, and lower 50-year-old or more than 50-year-old subgroups, with statistical differences (P<0.001), but there was no statistical difference in the group without LDCT screening (P=0.73). The sensitivity of the lung cancer high-risk population assessment model was 43.94% (116/264) and the specificity was 77.10% (127,275/165,073). The early diagnosis rate of the screening group was 72.97% (54/74), which was significantly higher than that of the non-screening group [28.48% (43/151)]. CONCLUSIONS The lung cancer high-risk population assessment model of National Key Public Health Program: Cancer Screening Program in Urban China can detect high-risk populations and improve the early diagnosis rate of lung cancer effectively.

Objective: To investigate the effects of p38 mitogen-activated protein kinases (p38 MAPK) inhibitor (SB203580) on airway inflammation in a mouse model of asthma. Methods: Forty-eight female BALB/c mice were randomly divided into four groups (n=12): control group, asthma group, dexamethasone group (2 mg/kg) and SB203580 group (5 mg/kg). Within 24 hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured by lung resistance (RL) and dynamic compliance (Cdyn). Bronchoalveolar lavage fluid (BALF) was collected for counting total cells, eosinophils, lymphocytes, neutrophils and macrophages. IgE and OVA-specific IgE in serum and IL-4, IL-5, IL-13 and IFN-γ in BALF were detected by ELISA. Lung tissues were stained with hematoxylin and eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) to observe histopathological changes. Expression of p38 MAPK and phosphorylated p38 (p-p38) MAPK was detected by immunohistochemical staining and Western blot, respectively. Results: (1) The mice in the asthma group showed typical symptoms of acute asthma after inhaling aerosolized OVA, while the symptoms were alleviated in those treated with dexamethasone or SB203580. (2) When challenged with the methacholine at the doses of 0.050 mg/kg, 0.100 mg/kg and 0.200 mg/kg, asthmatic mice treated with dexamethasone or SB203580 showed significantly decreased RL and increased Cdyn as compared with those in the asthma group (all P<0.05). (3) The concentrations of total IgE and OVA-specific IgE in serum in both dexamethasone and SB203580 groups were lower than those in the asthma group (all P<0.05). (4) Compared with the asthma group, the numbers of the total cells, eosinophil, lymphocytes and neutrophils in BALF were decreased in dexamethasone and SB203580 groups (all P<0.05). (5) Compared with the asthma group, the dexamethasone and SB203580 groups showed lower levels of IL-4, IL-5 and IL-13, but higher levels of IFN-γ in BALF (all P<0.05). (6) Dexamethasone or SB203580 significantly decreased the hyperemia and edema in airway mucosa, reduced the infiltration of inflammatory cells in the peribronchial areas and alleviated the tracheal epithelium goblet cell metaplasia in asthmatic mice. (7) Treatment with dexamethasone or SB203580 inhibited OVA-induced phosphorylation of p38 MAPK in asthmatic mice as revealed by immunohistochemical staining (both P<0.05). No significant difference in the expression of p38 MAPK was observed among the four groups (all P>0.05). (8) Expression of p-p38 MAPK at protein level in both dexamethasone and SB203580 groups was lower than that in asthma group (both P<0.05). Conclusion SB203580 regulated the Th1/Th2 balance through inhibiting the activation of p38 MAPK signaling pathway to alleviate OVA-induced airway inflammation.

Objective To analyze the diagnostic status of haemophilia in Chinese children in recent years,and to provide information for increasing the life quality of children with haemophilia in China.Methods The pediatric haemophilia cases registration data were collected and analyzed by using questionnaire,from January 1,2008 to March 30,2014 in 13 haemophilia treatment centers of haemophilia treatment center collaboration network of China pediatric group.These centers were from 12 provinces / municipalities.Results A total of 554 cases were collected;median age was 7.0 years old(0.1 to 17.9 years old);among them,481 cases(86.8％) were hemophilia A,and 73 cases were hemophilia B (13.2％);55 mild cases (9.9％),290 moderate cases (52.4％),and 209 severe cases (37.7％);162 cases(29.2％) had family history,the other 392 cases(70.8％) had no family history.The diagnosis was made at a median age of 12.0 month-old(0 to 180.0 months);the diagnosis time was 0.5 months(0 to 144.0 months) after the first bleeding;diagnosis timing with short interval was in 356 cases(64.3％),long interval was in 198 cases(35.7％).The diagnostic timing was not correlated with disease severity (P =0.812) or the family history (P =0.243);but correlated with the severity of first bleeding(P =0.027) and per capita gross domestic product (P ＜ 0.01) in patients' residence.From 1996 to 2013,the annual number of newly diagnosed cases was increasing year by year,with a higher proportion of short interval of diagnose timing.Conclusions With development of hemophilia work in China,the number of diagnosis of haemophilia children is increasing year by year.Moderate and severe hemorrhage are both taken seriously and diagnosed timely.But the diagnosis is delayed in some children.Chinese haemophilia work still need to be strengthen and the propaganda and diagnostic technology are to be popularized.

Objective To investigate the status and influencing factors of infusion-related adverse events in third-party cord blood stem cell infusion. Methods A total of 305 patients successfully underwent haploidentical stem cell transplantation combined with the third-party cord blood(CB) infusion,were recruited by convenience sampling from January 2013 to December 2015,in hematological department of a tertiary hospital in Suzhou. A self-developed questionnaire and adverse event assessment scale were used to investigate the influencing factors. Results The rate of infusion-related adverse events was 49.51%,81.82% were related to cardiovascular adverse events with the high-est rate of hypertension(76.14%). Logistic regression analysis showed that age(OR=1.030,95CI%:1.010-1.051),HLA matching between CB and receptor (OR=0.589,95%CI:0.413-0.838),thawed CB cell activity (OR=1.064,95%CI:1.015-1.115)were major influencing factors. Conclusion Nurses should pay attention to patients who are elderly,with low matching HLA and receive thawed CB product with high cell activities,and provide timely nursing care in advance.