[Quality Control Indexes for Oncology (2023 edition) and hot topics in breast surgery].

The National Health Commission of the People's Republic of China has formulated the Quality Control Indexes for Oncology (2023 edition), with the objective of improving medical quality scientifically, refined and standardized. Among these indexes, the rate of pretreatment clinical TNM staging and the coincidence rate of evaluation of pretreatment TNM staging lay national standards for patients to formulate rational and targeted treatment strategies. This article reviewed the literature and referred to Chinese Medical Association Clinical Practice Guide for Breast Surgery, and presented recommendations for the hot topics of breast surgery, such as pathological sampling of the breast specimen, sentinel lymph node biopsy for early-stage breast cancer, breast conserving surgery, axillary lymph node dissection, breast reconstruction surgery, endoscopic-assisted breast surgery, the principles of surgical treatment for metastatic breast cancer, neoadjuvant treatment for advanced disease, and surgical grade of breast surgery, which have been widely concerned in recent years, to help improve homogenization of breast cancer treatment in China.

Dual-energy CT perfusion imaging for differentiating invasive thymomas, thymic carcinomas, and lymphomas in adults.

AIM: To evaluate the role of dual-energy computed tomography perfusion (DECTP) imaging in differentiating invasive thymomas (ITs), thymic cancers (TCs), and lymphomas in adults. MATERIALS AND METHODS: Ninety-five patients with solid masses in the prevascular mediastinum who underwent DECTP examinations were enrolled in this study. The perfusion parameters (blood flow, BF; blood volume, BV; mean transit time, MTT; permeability surface, PS) and spectral parameters (water concentration, WC; iodine concentration, IC; normalised iodine concentration, NIC; the slope of spectral radiodensity [Hounsfield units] curve, λHU) of the lesions were analysed. RESULTS: There were no differences in the MTT or WC values among ITs, TCs, and lymphomas (all p>0.05). The IC, NIC, and λHU values in the optimal arterial and venous phases and PS values of TCs were higher than those of ITs and lymphomas (all p<0.05), and there were no differences between ITs and lymphomas (all p>0.05). The BF and BV values of lymphomas were lower than those of ITs and TCs (all p<0.05), and there were no differences between ITs and TCs (all p>0.05). The cut-off values for BF and BV used to differentiate lymphomas from ITs and TCs were 42.83 ml/min/100 g and 4.66 ml/100 g, respectively (area under the receiver operating characteristic curve: 0.847 and 0.839; sensitivity, 80.6% and 82.1%; specificity, 75% and 71.4%; accuracy, 78.9% and 81.1%). CONCLUSIONS: The perfusion and spectral parameters of DECTP imaging help to identify ITs, TCs, and lymphomas, and BF and BV values help to differentiate lymphomas from ITs and TCs.

Twenty-year changes in mortality rates and underlying causes of death in patients with rheumatoid arthritis-associated interstitial lung disease.

Objectives: Despite recent advances in the treatment of rheumatoid arthritis (RA), few population-based studies have assessed the mortality rates and the underlying causes of death (UCDs) among patients with RA and RA-associated interstitial lung disease (RA-ILD). This study evaluated the trends in mortality rates, demographic characteristics, and UCDs among patients with RA-ILD.Method: Using data from death certificates (1999-2018) from the US Centers for Disease Control and Prevention Multiple Cause of Death files, we explored the trends in mortality rates and UCD for patients with RA and RA-ILD. Moreover, we examined the crude and age-standardized mortality rates (ASMRs) for such patients.Results: Among patients with RA or RA-ILD, ASMR variation decreased over 20 years. The ASMR ratio of RA-ILD to RA decreased by 5.84%. The ASMR for RA and RA-ILD stratified by gender or age group also decreased. The change in the ASMR ratio of RA-ILD to RA trended downwards in women and upwards in men. Arthropathies and ILD were the most frequent UCDs for RA-ILD, while arthropathies and ischaemic heart disease were the most frequent UCDs for RA.Conclusions: Although RA and RA-ILD presented a downward trend in mortality, RA combined with ILD may reduce life expectancy. Specifically, the mortality rate for patients with RA-ILD remained relatively stable during the study period when ILD was the UCD, suggesting the need for active prevention, early diagnosis, and effective management of RA-ILD.

Digital learning in medical education: comparing experiences of Malaysian and Japanese students.

BACKGROUND: Medical education has undergone a transformation from conventional to digital learning, enabling learning without any time and place restrictions. Nevertheless, the actual trends of usage and its impact on learning motivation among medical students between developed and developing nations are yet to be investigated. Hence, this study compares the effect of digital learning on learning motivation among Malaysian and Japanese medical students in Universiti Kebangsaan Malaysia (UKM) and Shiga University of Medical Science (SUMS) respectively. METHODS: A modified Students Motivation towards Science Learning (SMTSL) was used to assess the digital learning usage and learning motivation among 150 UKM and 147 SUMS medical students throughout Year 1 to 5. RESULTS: The frequency of digital learning usage and learning motivation among UKM medical students was significantly higher as compared to SUMS (p < 0.001). Electronic books (e-books) were the most preferred source of digital learning among UKM medical students as compared to SUMS medical students who used research articles, e-books, online courses and videos at similar frequencies. UKM medical students in the clinical phase exhibited a significantly higher learning motivation as compared to preclinical students (p < 0.05) but not among SUMS medical students. CONCLUSION: A suitable learning environment should be developed to encourage digital learning usage among different levels of medical students to enhance its complementary role in medical education and augment the level of motivation among medical students in continuous lifelong learning.

[A retrospective evaluation of clinicalopathologic characteristics and prognostic factors for synchronous bilateral breast cancer in a single center].

Objective: To investigate the clinicopathologic features of synchronous bilateral breast cancer (SBBC) and prognostic factors. Methods: The clinicopathologic features of patients with SBBC treated in Peking University First Hospital from January 2008 to March 2019 were retrospectively analyzed. Results: Of all 4 111 patients diagnosed with breast cancer, 57(1.4%) cases were diagnosed with SBBC.Forty-three (75.4%) patients were treated with bilateral mastectomy. The median follow-up time was 58 months. The 5-year disease-free survival of SBBC was 80.7% and 5-year overall survival was 84.1%. The N stage and HER2 status of second primary breast cancer were associated with prognosis by univariated analysis (Z=5.866 and 4.231, both P<0.05). Conclusion: Majority of patients with SBBC were treated with bilateral mastectomy. While therapeutic strategy of SBBC should take both tumor burden and biomarker status of bilateral breast cancer into consideration.

[Docetaxel, carboplatin plus trastuzumab as neoadjuvant setting in patients with early-stage human epidermal growth factor receptor 2 positive breast cancer: a retrospective analysis].

Objective: To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer. Methods: Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison. Results: Patients who received trastuzumab-based therapy(n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab(n=177) (84.4% vs. 72.4%, χ²=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ²=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ²=1.008, P=0.315). Conclusions: TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.

Critical Role of Macrophage FcγR Signaling and Reactive Oxygen Species in Alloantibody-Mediated Hepatocyte Rejection.

Humoral alloimmunity negatively impacts both short- and long-term cell and solid organ transplant survival. We previously reported that alloantibody-mediated rejection of transplanted hepatocytes is critically dependent on host macrophages. However, the effector mechanism(s) of macrophage-mediated injury to allogeneic liver parenchymal cells is not known. We hypothesized that macrophage-mediated destruction of allogeneic hepatocytes occurs by cell-cell interactions requiring FcγRs. To examine this, alloantibody-dependent hepatocyte rejection in CD8-depleted wild-type (WT) and Fcγ-chain knockout (KO; lacking all functional FcγR) transplant recipients was evaluated. Alloantibody-mediated hepatocellular allograft rejection was abrogated in recipients lacking FcγR compared with WT recipients. We also investigated anti-FcγRI mAb, anti-FcγRIII mAb, and inhibitors of intracellular signaling (to block phagocytosis, cytokines, and reactive oxygen species [ROS]) in an in vitro alloantibody-dependent, macrophage-mediated hepatocytoxicity assay. Results showed that in vitro alloantibody-dependent, macrophage-mediated hepatocytotoxicity was critically dependent on FcγRs and ROS. The adoptive transfer of WT macrophages into CD8-depleted FcγR-deficient recipients was sufficient to induce alloantibody-mediated rejection, whereas adoptive transfer of macrophages from Fcγ-chain KO mice or ROS-deficient (p47 KO) macrophages was not. These results provide the first evidence, to our knowledge, that alloantibody-dependent hepatocellular allograft rejection is mediated by host macrophages through FcγR signaling and ROS cytotoxic effector mechanisms. These results support the investigation of novel immunotherapeutic strategies targeting macrophages, FcγRs, and/or downstream molecules, including ROS, to inhibit humoral immune damage of transplanted hepatocytes and perhaps other cell and solid organ transplants.

[Phenylpropanoid glycosides from Sophorae Tonkinensis Radix et Rhizoma].

Three phenylpropanoid glycosides were purified by extensive chromatographic techniques including column chromatography over microporous resin, MCI, diol, sephadex LH-20, reverse phase C_(18) from water-extracts of Sophorae Tonkinensis Radix et Rhizoma. Their planar structures were elucidated by combination of various spectroscopic method, such as IR, UV, MS, and NMR. The absolute configuration of aglycone was determined by quantum chemical calculations. Their structures were elucidated as(8R)-3-(4-hydroxyphenyl)-1-propanol-2-O-ß-D-glucopyranoside(1), kalopanaxin D(2),(E)-4-hydroxycinnamyl alcohol 4-O-[2'-O-ß-D-apiofuranosyl(1″→2')]-ß-D-glucopyranoside(3). Compound 1 was undescribed previously. Compounds 2 and 3 were firstly isolated from Sophora genus.

[Proteomics analysis of erythrocyte membrane in rats with high altitude polycythemia before and after intervention with salidroside].

To investigate the effect of salidroside on the proteomics of erythrocyte membrane in high altitude erythrocytosis(HAPC) rats, in order to explore the mechanism of salidroside in improving HAPC based on the proteomics analysis. First, HPAC rat models were established, and 16 rats were randomly divided into HAPC model group and salidroside(100 mg·kg~(-1)) treatment group(8 rats per group). Saline was administered to the HAPC model group, while salidroside treatment group was given 100 mg·kg~(-1) salidroside once a day. After continuous oral administration with salidroside for 40 days(once a day), blood was collected from the femoral artery to obtain total red blood cell membrane proteins. Two-dimensional electrophoresis was used to separate total proteins. The two-dimensional electrophoresis of erythrocyte membrane proteins was analyzed before and after salidroside intervention, and the proteins with significant differences were identified by mass spectrometry. Finally, biological functions were analyzed using bioinformatics. A two-dimensional electrophoresis method was used to establish a protein expression profile with a high resolution and reproducibility of erythrocyte membranes in HAPC rats. Salidroside treatment significantly changed 18 protein spots in the 2-DE map of erythrocyte membranes, of which 13 proteins were up-regulated and 5 proteins were down-regulated. Eight differential proteins were successfully identified by mass spectrometry. Moreover, bioinformatics analysis found that these differential proteins were involved in such biological processes as oxidative stress, redox, and peroxisome pathway, which are mainly associated with peroxisome and MAPK signaling pathways. Therefore, salidroside could significantly change the expressions of erythrocyte membrane proteins in HAPC rats. Eight differential proteins were identified by a proteomic-based approach. The differential proteins were involved in such biological processes as oxidative stress, redox, peroxisome pathway.

[Moxa nitrogen content determination and its application in moxa floss grade identification].

Artemisia argyi samples were collected from different areas in Hubei Qichun and medicinal botanical garden of Hubei University of Traditional Chinese Medicine, and samples were purchased from different areas in Qichun medicinal market. The same method was used to prepare A. argyi samples from different areas into moxa floss of different leaf velvet ratio. The nitrogen content of A. argyi was determined by Kjeldahl method. The results show that there was an inverse relationship between the content of nitrogen and the level of the leaf velvet ratio grades of moxa floss and nitrogen content. Therefore, six functional models were established to illustrate the relationship between the grades of leaf velvet ratio and nitrogen content. The accuracy of the functional models was evaluated by ■. The cubic function model and exponential function model are selected as the best models and the formula is: Y_(grades)=-4.26 N~3+26.09 N~2-61.09 N+55.84, Y_(grades)=63.68×10~(-1.374N), with R~2 values of 0.976 5 and 0.969 6, respectively. The accuracy reached above 95% of the two function models when verified by laboratory-made moxa floss, while the accuracy of the models was 85.44% when verifed by commercial moxa floss. These results indicate that the model could be applied to the identification of the grades of moxa floss.

Evolving role of Instagram in #medicine.

Social media has become an integral part of daily life and its use is becoming increasingly intertwined with the healthcare sector. Instagram is a free photo and video sharing social media application that has been utilised extensively in visually rich fields within medicine. Herein, we discuss the advantages and disadvantages of its use in modern medicine.

[Breast reconstruction after mastectomy in breast cancer patients: specialization and standardization].

In recent years, with the improvement of screening and early diagnosis, the overall prognosis of breast cancer patients has been greatly improved in China. Breast reconstruction is an option to improve cosmetic outcomes and quality of life for the patients received mastectomy, this procedure has attracted a lot of attention. The breast reconstruction surgery is recommended by the 2018 NCCN Clinical Practice Guidelines in Oncology for Breast Cancer in patients with appropriate indications. Despite the high proportion of breast reconstruction after mastectomy in western countries, Chinese breast surgeon should objectively understand the differences in breast structure and cultural backgrounds between Chinese and foreign women, and conduct rigorous clinical practice on the basis of calm thinking. In particular, it should be clearly recognized that we have more local advanced and high-risk cases in newly diagnosed breast cancer patients. Making efforts to improve the overall survival for patients with breast cancer must be the top priority for our surgeon. Breast reconstruction for all patients without identifying the distinction of personal characters and indications should be avoided, and the pursuing of high proportion of clinical data with no consideration of the realities of clinical practice in China should also be avoided. The indication of breast reconstruction for breast cancer patients received mastectomy must be strictly determined by the surgeon.

[Evaluation of progression-free survival for locally advanced rectal cancer by MRI after neoadjuvant chemoradiotherapy and total mesorectal excision].

Objective: To evaluate the predictive value of MRI features and pathological parameters on local recurrence, metastasis and progression free survival (PFS) for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and subsequent total mesorectal excision surgery. Methods: A retrospective analysis of 95 patients with locally advanced rectal adenocarcinoma who underwent total mesorectal excision after neoadjuvant chemoradiotherapy was performed. Univariate and multivariate analyses were performed to evaluate the predictive value of MRI features before chemoradiation and postoperative pathological parameters on progression free survival. Results: Among the 95 cases, 5 cases occured local recurrence, 21 cases developed, 3 cases including both locally recurrence and distant metastasis, 19 died and 47 had no recurrence or metastasis at the last of follow-up. Univariant analysis showed that MRI signs before chemoradiation, namely, mr circumferential resection margin, mr levator ani muscle invasion, mr lymphatic vessel invasion, mr tumor deposition and postoperative pathological parameters, yp circumferential resection margin, yp lymphatic vessel invasion were related to PFS (P<0.05). Multivariate analysis of Cox proportional hazard model showed that mr lymphatic vessel invasion and mr tumor deposition were independent factors for PFS (OR=2.774 and 3.029, P<0.05). Conclusions: Lymphatic vessel invasion and tumor deposition on MRI are independent prognostic factors for progression free survival of locally advanced rectal cancer after neoadjuvant chemoradiotherapy and TME surgery. To some extent, MRI signs can assess local recurrence and distant metastasis in locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy and mesorectal excision.

[Analysis of neoadjuvant docetaxel, carboplatin and trastuzumab (TCH) in HER-2-positive breast cancer].

Objective: To analyze docetaxel (T) and carboplatin (C) combined with trastuzumab (H) -TCH regimen as neoadjuvant systemic therapy in early breast cancer patients with human epidermal growth factor receptor 2 (HER-2) positive. Methods: From January 2008 to December 2014, the data of patients diagnosed as early breast cancer in Breast Disease Center of Peking University First Hospital were retrospective reviewed. The data of patients with HER-2 positive conducted TCH neoadjuvant therapy and surgery, and with the complete clinicopathological information were analyzed. Results: A total of 77 cases were enrolled in this study. We defined G2+ G3+ G4+ G5 as responsive group according to Miller-Payne grading system, the responsive rate was 84.4% (65/77). The rate of complete pathological remission (pCR) was 39.0% (30/77). The 5-year disease free survival (DFS) was 87.3%, and 5-year overall survival (OS) was 93.6%. There was a significant difference between DFS and OS in the responsive group and non-responsive group (DFS: χ2=6.762, P=0.009; OS: χ2=5.062, P=0.024). Conclusion: TCH is an effective neoadjuvant therapy for patients with HER-2 positive breast cancer, and the toxic and side effects were under control.

[Current situation and prospect of breast cancer liquid biopsy].

Liquid biopsy is a diagnostic approach by analyzing body fluid samples. Peripheral blood is the most common sample. Urine, saliva, pleural effusion and ascites are also used. Now liquid biopsy is mainly used in the area of neoplasm diagnosis and treatment. Compared with traditional tissue biopsy, liquid biopsy is minimally invasive, convenient to sample and easy to repeat. Liquid biopsy mainly includes circulating tumor cells and circulating tumor DNA (ctDNA) detection. Detection of ctDNA requires sensitive and accurate methods. The progression of next-generation sequencing (NGS) and digital PCR promote the process of studies in ctDNA. In 2016, Nature published the result of whole-genome sequencing study of breast cancer. The study found 1 628 mutations of 93 protein-coding genes which may be driver mutations of breast cancer. The result of this study provided a new platform for breast cancer ctDNA studies. In recent years, there were many studies using ctDNA detection to monitor therapeutic effect and guide treatment. NGS is a promising technique in accessing genetic information and guiding targeted therapy. It must be emphasized that ctDNA detection using NGS is still at research stage. It is important to standardize ctDNA detection technique and perform prospective clinical researches. The time is not ripe for using ctDNA detection to guide large-scale breast cancer clinical practice at present.

Comparative genotoxicity of silver nanoparticles in human liver HepG2 and lung epithelial A549 cells.

With the rapid expanding of human exposure to silver nanoparticles (AgNPs), genotoxicity screening of nanosilver is necessary to ensure consumer safety. Here, we assessed one key DNA damage responsive pathway activated by GADD45a gene after 24 h of AgNPs exposure in stable luciferase reporter cell systems based on two widely used in vitro cell models, human liver HepG2 and lung epithelial A549 cells. The comet assay and micronucleus test were also conducted to confirm the genetic damage induced by AgNPs. Our results showed that AgNPs produced a strong dose-dependent increase in transcriptional activation of GADD45a promoter indicated by luciferase activity accompanying by the significant decreases in cell viability. Surprisingly, in HepG2-luciferase cells, the relative luciferase activity was greater than 4.5× the control level after being treated with 200 µg ml-1 AgNPs. These results were generally in line with the positive and dose-dependent responses in cytotoxicity, DNA strand breaks indicated by Olive tail moment, tail DNA (%) and tail length, and chromosome damage indicated by induction of micronuclei, nucleoplasmic bridges, and nuclear buds. Additionally, compared with the A549-luciferase cells, the HepG2-luciferase cells seemed to be more susceptible to AgNPs as higher levels of genotoxicity were induced. We concluded that our GADD45a promoter-driven luciferase reporter gene cell system, together with the comet assay and micronucleus test, can be used as valuable tools for rapid screening of genotoxic potential of nanosilver. Copyright © 2016 John Wiley & Sons, Ltd.

The Z-cad dual fluorescent sensor detects dynamic changes between the epithelial and mesenchymal cellular states.

BACKGROUND: The epithelial to mesenchymal transition (EMT) has been implicated in metastasis and therapy resistance of carcinomas and can endow cancer cells with cancer stem cell (CSC) properties. The ability to detect cancer cells that are undergoing or have completed EMT has typically relied on the expression of cell surface antigens that correlate with an EMT/CSC phenotype. Alternatively these cells may be permanently marked through Cre-mediated recombination or through immunostaining of fixed cells. The EMT process is dynamic, and these existing methods cannot reveal such changes within live cells. The development of fluorescent sensors that mirror the dynamic EMT state by following the expression of bona fide EMT regulators in live cells would provide a valuable new tool for characterizing EMT. In addition, these sensors will allow direct observation of cellular plasticity with respect to the epithelial/mesenchymal state to enable more effective studies of EMT in cancer and development. RESULTS: We generated a lentiviral-based, dual fluorescent reporter system, designated as the Z-cad dual sensor, comprising destabilized green fluorescent protein containing the ZEB1 3' UTR and red fluorescent protein driven by the E-cadherin (CDH1) promoter. Using this sensor, we robustly detected EMT and mesenchymal to epithelial transition (MET) in breast cancer cells by flow cytometry and fluorescence microscopy. Importantly, we observed dynamic changes in cellular populations undergoing MET. Additionally, we used the Z-cad sensor to identify and isolate minor subpopulations of cells displaying mesenchymal properties within a population comprising predominately epithelial-like cells. The Z-cad dual sensor identified cells with CSC-like properties more effectively than either the ZEB1 3' UTR or E-cadherin sensor alone. CONCLUSIONS: The Z-cad dual sensor effectively reports the activities of two factors critical in determining the epithelial/mesenchymal state of carcinoma cells. The ability of this stably integrating dual sensor system to detect dynamic fluctuations between these two states through live cell imaging offers a significant improvement over existing methods and helps facilitate the study of EMT/MET plasticity in response to different stimuli and in cancer pathogenesis. Finally, the versatile Z-cad sensor can be adapted to a variety of in vitro or in vivo systems to elucidate whether EMT/MET contributes to normal and disease phenotypes.

[Hot topics of circulating tumor DNA testing in breast cancer].

The progress of gene detection technologies represented by next generation sequencing (NGS) and digital PCR laid a foundation for studies of circulating tumor DNA (ctDNA) in breast cancer. In 2014, the NGS workgroup organized by the College of American Pathologists (CAP) published the College of American Pathologists' Laboratory Standards for Next-Generation Sequencing Clinical Tests, which provides a blueprint for the standardization of gene testing. In 2015, the Guidelines for Diagnostic Next-generation Sequencing published by the European Society of Human Genetics claimed that NGS is unacceptable in clinical practice before studies guided by guidelines are approved. Although existing studies show the benefits of ctDNA testing in disease monitoring and prognosis analyzing, we have a ways to go to normalize the procedure and build strict detection criteria.