Traction power systems for electrified railways:evolution,state of the art,and future trends

Traction power systems(TPSs)play a vital role in the operation of electrified railways.The transformation of conventional railway TPSs to novel structures is not only a trend to promote the development of electrified railways toward high-efficiency and resilience but also an inevitable requirement to achieve carbon neutrality target.On the basis of sorting out the power supply structures of conventional AC and DC modes,this paper first reviews the characteristics of the existing TPSs,such as weak power supply flexibility and low-energy efficiency.Furthermore,the power supply structures of various TPSs for future electrified railways are described in detail,which satisfy longer distance,low-carbon,high-efficiency,high-reliability and high-quality power supply requirements.Meanwhile,the application prospects of different traction modes are discussed from both technical and economic aspects.Eventually,this paper introduces the research progress of mixed-system electrified railways and traction power supply technologies without catenary system,speculates on the future development trends and challenges of TPSs and predicts that TPSs will be based on the continuous power supply mode,employing power electronic equipment and intelligent information technology to construct a railway comprehensive energy system with renewable energy.

Unveiling the therapeutic potential:KBU2046 halts triple-negative breast cancer cell migration by constricting TGF-β1 activation in vitro

Background:Triple-negative breast cancer(TNBC)is a heterogeneous,recurring cancer characterized by a high rate of metastasis,poor prognosis,and lack of efficient therapies.KBU2046,a small molecule inhibitor,can inhibit cell motility in malignant tumors,including breast cancer.However,the specific targets and the corresponding mechanism of its function remain unclear.Methods:In this study,we employed(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium)(MTS)assay and transwell assay to investigate the impact of KBU2046 on the proliferation and migration of TNBC cells in vitro.RNA-Seq was used to explore the targets of KBU2046 that inhibit the motility of TNBC.Finally,confirmed the predicted important signaling pathways through RT-qPCR and western blotting.Results:In this study,we found that KBU2046 functioned as a novel transforming growth factor-β(TGF-β1)inhibitor,effectively suppressing tumor cell motility in vitro.Mechanistically,it directly down-regulated leucine-rich repeat-containing 8 family,member E(LRRC8E),latent TGFβ-binding protein 3(LTBP3),dynein light chain 1(DNAL1),and MAF family of bZIP transcription factors(MAFF)genes,along with reduced protein expression of the integrin family.Additionally,KBU2046 decreased phosphorylation levels of Raf and ERK.This deactivation of the ERK signaling pathway impeded cancer invasion and metastasis.Conclusions:In summary,these findings advocate for the utilization of TGF-β1 as a diagnostic and prognostic biomarker and as a therapeutic target in TNBC.Furthermore,our data underscore the potential of KBU2046 as a novel therapeutic strategy for combating cancer metastasis.

Adjuvant tamoxifen switched to exemestane treatment in postmenopausal women with estrogen receptor-positive early breast cancer:A pragmatic,multicenter,and prospective clinical trial in China

Objective:This post-approval safety study assessed the efficacy and safety of exemestane after 2-3 years of tamoxifen treatment among postmenopausal women with estrogen receptor-positive(ER+)early breast cancer in China.Methods:Enrolled patients had received 2-3 years of tamoxifen and were then switched to exemestane for completion of 5 consecutive years of adjuvant endocrine therapy.The primary endpoint was the time from enrollment to the first occurrence of locoregional/distant recurrence of the primary breast cancer,appearance of a second primary or contralateral breast cancer,or death due to any cause.Other endpoints included the proportion of patients experiencing each event,incidence rate per annum,relationships between human epidermal growth factor receptor 2 status and time to event,and relationship between disease history variables and time to event.Results:Overall,558 patients were included in the full analysis set:397(71.1%)completed the study,20experienced an event,and 141 discontinued[47 owing to an adverse event(AE);37 no longer willing to participate].Median duration of treatment was 29.5(range,0.1-57.7)months.Median time to event was not reached.Eventfree survival probability at 36 months was 91.4%(95%CI,87.7%-95.1%).The event incidence over the total exposure time of exemestane therapy was 3.5 events/100 person-years(20/565).Multivariate analysis showed an association between tumor,lymph node,and metastasis stage at initial diagnosis and time to event[hazard ratio:1.532(95%CI,1.129-2.080);P=0.006].Most AEs were grade 1 or 2 in severity,with arthralgia(7.7%)being the most common treatment-related AE.Conclusions:This study supports the efficacy and safety of exemestane in postmenopausal Chinese women with ER+breast cancer previously treated with adjuvant tamoxifen for 2-3 years.No new safety signals were identified in the Chinese population.

Application of Grey Theory to Ionospheric Short-term Forecasting

By analysis of historical data of the ionosphere, it is suggested to apply grey theory to ionospheric short-term forecasting, grey range information entropy is defined to determine the optimum grey length of the sample sequence, the prediction model based on residual error is constructed, and the observation data of multiple ionospheric observation stations in China are adopted for test. The prediction result indicates that the average grey range information entropy calculation results reflect the cyclical effects of solar rotation, precision of the forecasting method in high latitudes is higher than low latitudes, and its error is large relatively in more intense solar activity season, the effect of forecasting 1 day in advance of average relative residuals are less than 1 MHz, the average precision is more than 90%. It provides a new way of thinking for the ionospheric foF2 short-term forecast in the future.

Urban Rural Disparity in Westernization Related Cancers and the Increasing Incidence in Parallel with Socioeconomic Development and Urbanization from 2000-2015 among a Rural Chinese Population: An Observational Study

Abstract China used to have great urban rural disparity in socioeconomic development. Since the late 1980s, rapid socioeconomic development and urbanization have been taking place in rural settings. It is epidemiologically established that cancer scale and profile will transit as economy prospers and urbanization develops. However, there are few published studies reporting what changes are undergoing in cancer pattern in Chinese rural settings. Population-based tumor registration data collected by us in urban Shijiazhuang city (available for 2,374,827 people in 2012) and in rural Shexian County (available for 408,995 people since 2000) were used for urban rural comparison of age standardized incidence rate (ASIR) of westernization-related cancers in 2012, and the trend of biennial ASIR of these cancers for 2000-2015 in Shexian County was examined following a decade of rapid socioeconomic development and urbanization. From 1988-2015, the Gross Domestic Product per Capita (GDP) in rural Shexian County increased from 860 to 3000 US$, and urbanization rate from 22.4% to 54.8%. The biennial ASIRs of lung, colorectal, gallbladder cancer and leukemia in both sexes, and that of breast, ovary, thyroid, and kidney cancer in women increased significantly from 2000 - 2015. The increase from 2000-2001 to 2014-2015 in man and women for lung cancer was from 15.9 to 34.7 per 105 (P = 0.05) and 9.6 to 16.7 (P = 0.00), for colorectal cancer from 6.6 to 15.9 (P = 0.00) and 4.0 to 11.7 (P = 0.00), for gallbladder cancer from 0.1 to 2.4 (P = 0.00) and 0.3 to 2.7 (P = 0.00), for leukemia from 2.8 to 7.7 (P = 0.00) and 2.3 to 6.2 (P = 0.00);and in women for cancer of breast from 2.8 to 17.3 (P = 0.00), kidney from 0.2 to 2.4 (P = 0.00), ovary from 0.2 to 4.3 (P = 0.00), and thyroid from 0.2 to 4.2 (P = 0.00). Notwithstanding these increases, their ASIRs in 2012 in Shexian County were still significantly lower than that in Shijiazhuang city. Westernization-related cancer is increasing rapidly in rural China. Comprehensive measures are needed to strengthen prevention to ensure sustainable development.

Disitamab vedotin,a HER2-directed antibody-drug conjugate,in patients with HER2-overexpression and HER2-low advanced breast cancer:a phase I/Ib study

Background:Disitamab vedotin(DV;RC48-ADC)is an antibody-drug conjugate comprising a human epidermal growth factor receptor 2(HER2)-directed antibody,linker and monomethyl auristatin E.Preclinical studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast,gastric,and ovarian cancers with different levels of HER2 expression.In this pooled analysis,we report the safety and efficacy of DV in patients with HER2-overexpression and HER2-low advanced breast cancer(ABC).Methods:In the phase I dose-escalation study(C001 CANCER),HER2-overexpression ABC patients received DV at doses of 0.5-2.5 mg/kg once every two weeks(Q2W)until unacceptable toxicity or progressive disease.The dose range,safety,and pharmacokinetics(PK)were determined.The phase Ib dose-range and expansion study(C003 CANCER)enrolled two cohorts:HER2-overexpression ABC patients receiving DV at doses of 1.5-2.5 mg/kg Q2W,with the recommended phase 2 dose(RP2D)determined,andHER2-lowABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2-low ABC.Results:Twenty-four patients with HER2-overexpression ABC in C001 CANCER,46 patients with HER2-overexpressionABCand 66 patients with HER2-low ABC in C003 CANCER were enrolled.At 2.0 mg/kg RP2D Q2W,the confirmed objective response rates were 42.9%(9/21;95%confidence interval[CI]:21.8%-66.0%)and 33.3%(22/66;95%CI:22.2%-46.0%),with median progression-free survival(PFS)of 5.7 months(95%CI:5.3-8.4 months)and 5.1 months(95%CI:4.1-6.6 months)for HER2-overexpression and HER2-low ABC,respectively.Common(≥5%)grade 3 or higher treatment-emergent adverse events included neutrophil count decreased(17.6%),gamma-glutamyl transferase increased(13.2%),asthenia(11.0%),white blood cell count decreased(9.6%),peripheral neuropathy such as hypoesthesia(5.9%)and neurotoxicity(0.7%),and pain(5.9%).Conclusion:DV demonstrated promising efficacy in HER2-overexpression and HER2-low ABC,with a favorable safety profile at 2.0 mg/kg Q2W.

Association of a complete breast cancer pathologic response with axillary lymph node metastasis via neoadjuvant chemotherapy:Results from the CSBrS-012 study

To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.

CACA Guidelines for Holistic Integrative Management of Breast Cancer

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Clinical evaluation of the first domestically produced generic isosulfan blue injection in sentinel lymph node biopsy for early breast cancer in China:a multicenter,single-arm,open validation trial(CSBrS-024)

In 2020,the first generic isosulfan blue product for injection(notification number:2020 LP00901,batch number:118210301,5 mL:50 mg,Guangdong Hebo Pharmaceutical Co.,Ltd.)was approved by the National Medical Products Administration of China.This multicenter,single-arm,phase III,open clinical validation trial was organized by the Chinese Society of Breast Surgery to evaluate the efficacy and safety of this domestically produced generic isosulfan blue injection for sentinel lymph node biopsy(SLNB)in patients with early breast cancer(BC)in China.

Clinical practice guidelines for the diagnosis and treatment of inflammatory breast cancer:Chinese Society of Breast Surgery(CSBrS)Practice Guidelines 2022

To improve the diagnosis and treatment of inflammatory breast cancer(IBC),the Chinese Society of Breast Surgery(CSBrS)of the Chinese Medical Association identified the key clinical issues for clinical practice guidelines through literature research and evaluated the relevant evidence with reference to the Grading of Recommendations Assessment,Development and Evaluation(GRADE).[1]Level of evidence standard and recommendation strength criteria are shown in previous publication.[2]Recommendation strength review committee was comprised of 31 members and all the members are breast surgeons.The target audience are Chinese breast disease specialists.The recommendation is shown in Table 1.