Teaching Reform and Practice of Functional Experiment Based on the Cultivation of Excellent Medical Talents

In order to cultivate excellent clinical medical talents with a solid foundation, strong literacy, refined skills, excellent communication abilities, innovative thinking, and a strong focus on practicality, functional experiments have undergone a series of reforms in areas such as constructing new curriculum systems, improving teaching content, updating teaching equipment, introducing new teaching models, and enhancing teaching evaluation systems.

预测儿童Ⅱ期人工晶状体植入术后青光眼相关不良事件的风险:一项为期3年的研究

目的:建立并评估儿童Ⅱ期人工晶状体(intraocular lens,IOL)植入术后青光眼相关不良事件(glaucomarelated adverse events,GRAEs)的预测模型。方法:选取于中山大学中山眼科中心行Ⅱ期IOL植入术的无晶状体眼患儿205例(356眼),并在术后对其随访3年。采用Cox比例风险模型确定GRAEs的预测因子,并建立列线图预测模型。采用随时间变化的受试者工作特征(receiver operating characteristic,ROC)曲线、决策曲线分析、Kaplan-Meier曲线评估模型性能,并通过Bootstrapping的C指数和校准图进行内部验证。结果:行Ⅱ期IOL植入术时年龄较大(HR=1.50,95%CI:1.03~2.19)、术后一过性高眼压(HR=9.06,95%CI:2.97~27.67)和IOL睫状沟植入术(HR=14.55,95%CI:2.11~100.57)是GRAEs的危险因素(均P<0.05),并据此建立了两个列线图预测模型。在术后1、2、3年,模型1的ROC曲线下面积(area under curve,AUC)分别为0.747(95%CI:0.776~0.935)、0.765(95%CI:0.804~0.936)和0.748(95%CI:0.736~0.918),模型2的AUC分别为0.881(95%CI:0.836~0.926)、0.895(95%CI:0.852~0.938)和0.848(95%CI:0.752~0.945)。在内部验证和评价中,两种模型均表现出良好的性能和临床净效益。Kaplan-Meier曲线显示两个不同的风险组在两个模型中都能被显著且稳健地区分。此外,本研究也构建了在线风险计算器。结论:两种列线图均能灵敏、准确地识别Ⅱ期IOL植入术后GRAEs的高危患儿,有助对其进行早期识别和及时干预。

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Exploration on Teaching Reform of Medical Functional Experimental Science for International Students

Medical Functional Experiment Science, a bridge between basic medicine and clinical medicine, integrates classical experimental teaching contents of three courses including physiology, pathophysiology and pharmacology. This course not only helps students to verify and reinforce theoretical knowledge, but also cultivates their capability of scientific thinking to discover and solve problems. Based on the characteristics of international students and current situation of the teaching platform in the laboratory at Yangtze University, this paper discusses a series of problems in the Medical Functional Experiment Science teaching for international students and puts forward some measures for teaching reform including optimizing experimental content, innovating experimental teaching methods and establishing effective experimental evaluation mode, in order to cultivate more international medical students with innovative ability.

Exploration of the Exceptional Capacitive Deionization Performance of CoMn_(2)O_(4) Microspheres Electrode

The“battery type”inorganic electrode has been demonstrated the highly efficient sodium ion intercalation capacity for capacitive deionization.In this work,the CoMn_(2)O_(4)(CMO)microspheres with porous core-shell structure are prepared via co-precipitation and followed by annealing.The effects of annealing temperatures on the morphology,pore structure,valence state,and electrochemical behavior of CMO are explored.As electrode for capacitive deionization,the salt removal capacity and current efficiency of optimized AC||CMO device reaches up to 60.7 mg g^(−1) and 97.6%,respectively,and the capacity retention rate is 74.1%after 50 cycles.Remarkably,both the in-situ X-ray diffraction and ex-situ X-ray diffraction analysis features that the intercalation/de-intercalation of sodium ions are governed by(103)and(221)crystal planes of CMO.Accordingly,the density functional theory calculations realize that the adsorption energies of Na+onto(103)and(221)crystal planes are higher than that of any other crystal planes,manifesting the priorities in adsorption of sodium atoms.Furthermore,the X-ray photoelectron spectra of pristine and post-CMO electrode highlights that the reversible conversion of Mn^(3+)/Mn^(4+)couple is resulted from the intercalation/de-intercalation of Na^(+),while this is irreversible for Co^(3+)/Co^(2+)couple.Beyond that,the CMO electrode has been proven the selectivity removal of Na^(+) over K^(+)and Mg^(2+)in a multi-cation stream.

Evolution and trends of high myopia research from 2002 to 2021: a scientometric analysis

Background:Research on high myopia has gradually formed a complex network of knowledge,but a panorama of evolutionary trends is lacking.By conducting a scientometric analysis,we can gain a deeper understanding of the development and evolution of this field.Methods:The global literature on high myopia published from 2002 to 2021 was extracted from the Science Citation Index Expanded in the Web of Science Core Collection.Microsoft Excel,VOSviewer,and CiteSpace were used to analyse and visualize the bibliometric data.Publication-related information,including countries,journals,authors,citations,subject categories,and its’time trends,was analysed.Results:A total of 4,226 included publications showed an annually increasing trend during the past 20 years.The high myopia research hotspots were refractive error correction,epidemiology,ocular biometry,drug and laser treatment of myopic fundus lesions,and surgical treatment of myopic fundus lesions.Cocitation analysis showed that high myopia genetics and myopic fundus lesion research were the research frontiers.A total of 116 disciplines were involved in high myopia research.Ophthalmology(n=3,338)was the most dominant subject category.Engineering(betweenness centrality=0.65)was the discipline with the most obvious bridge role.Science&technology—other topics(burst years:2015–2021;strength=14.88)had the greatest strength as of 2021,which was the hottest subject category.Conclusions:High myopia genetics and myopic fundus lesion research showed a potential for breakthroughs.Medical-engineering cross-innovation is a cutting-edge technology trend.

QC_(0.44)-g-PLA两亲性共聚物合成及自组装纳米胶束在疏水性药物水系载体中的应用

在绿色溶剂1-丁基-3-甲基咪唑氯盐中,通过纤维素季铵盐的羟基与疏水单体乳酸(LA)之间的开环接枝聚合反应(ROP),在二甲氨基吡啶(DMAP)或1,8-二氮杂二环十一碳-7-烯(DBU)的催化作用下制备QC_(0.44)-g-PLA两亲性共聚物。利用红外光谱、核磁共振、X射线衍射、热重分析、透射电镜、粒径分布和荧光光谱等技术对QC_(0.44)-g-PLA共聚物的结构、性能及自组装行为进行表征。透射电镜和粒径分布结果表明,QC_(0.44)-g-PLA共聚物在水溶液中可自组装成均一球形纳米胶束,其粒径为92~226 nm,疏水链段PLA的摩尔取代度(MS)为0.83~2.54,共聚物临界胶束浓度(CMC)为215~272μg/m L,胶束的粒径和CMC值均随MS的增加而降低。胶束表面电荷呈阳电性,并且对紫杉醇(PTX)和吴茱萸碱(EVO)的包封率随共聚物中PLA的MS值增加而增加,其最大包封率分别为69.7%和66.4%。

Evaluation of a deep-learning model for multispectral remote sensing of land use and crop classification

High-resolution deep-learning-based remote-sensing imagery analysis has been widely used in land-use and crop-classification mapping. However, the influence of composite feature bands, including complex feature indices arising from different sensors on the backbone, patch size, and predictions in transferable deep models require further testing. The experiments were conducted in six sites in Henan province from2019 to 2021. This study sought to enable the transfer of classification models across regions and years for Sentinel-2 A(10-m resolution) and Gaofen PMS(2-m resolution) imagery. With feature selection and up-sampling of small samples, the performance of UNet++ architecture on five backbones and four patch sizes was examined. Joint loss, mean Intersection over Union(m Io U), and epoch time were analyzed, and the optimal backbone and patch size for both sensors were Timm-Reg Net Y-320 and 256 × 256, respectively. The overall accuracy and Fscores of the Sentinel-2 A predictions ranged from 96.86% to 97.72%and 71.29% to 80.75%, respectively, compared to 75.34%–97.72% and 54.89%–73.25% for the Gaofen predictions. The accuracies of each site indicated that patch size exerted a greater influence on model performance than the backbone. The feature-selection-based predictions with UNet++ architecture and upsampling of minor classes demonstrated the capabilities of deep-learning generalization for classifying complex ground objects, offering improved performance compared to the UNet, Deeplab V3+, Random Forest, and Object-Oriented Classification models. In addition to the overall accuracy, confusion matrices,precision, recall, and F1 scores should be evaluated for minor land-cover types. This study contributes to large-scale, dynamic, and near-real-time land-use and crop mapping by integrating deep learning and multi-source remote-sensing imagery.

Effect of K1, K2 Anti-Bacterial Agents on Tobacco Ralstonia Solanacearum

The tobacco Ralstonia Solanacearum were both cultured on nutrient agar plates and inoculated in seedling stage of tobacco, then treated with K1 and K2, two anti-bacterial agents, at a serial con-centrations to study their inhibitory efficiency. The result indicated that K1 can inhibit R. Solanacearum growth entirely, at the concentration range from 1/50 to 1/5000. K2 can reach the same result at the concentration range from 1/50 to 1/50000. Compared with the control plates, K1, at the concentration 1/50000, had no significant differences, and the average number of colony per plate was 112-115. The immature tobacco shown wilt as soon as inoculated with R. Solanacearum, and recovered gradually after using K1, K2. The densities of microbial suspension, handled by K1, K2 within 10 hs, were both significantly lower than the controlled ones. The optical microscopy also shown that handled microbial body differed from the controlled, whose body was regular short, rod shape as opposed to the handled ones with irregular rod shape and damaged body. All the results indicated that K1 and K2 both had inhibitory effects on tobacco R. Solanacearum, and K2 was more efficient than K1.

Is proton a charge carrier for δ-MnO_(2) cathode in aqueous rechargeable magnesium-ion batteries?

Manganese dioxide(MnO_(2)) is considered as a potential cathode material for aqueous magnesium-ion batteries. However, the charge/discharge mechanism of MnO_(2)in aqueous electrolyte is still unclear. In present study, highly porous δ-MnO_(2) is investigated, which delivers a high capacity of 252.1 m Ah g^(-1) at 0.05 A g^(-1) and excellent rate capability, i.e., 109.7 m Ah g^(-1) at 1 A g^(-1), but a low-capacity retention of 54.4% after 800 cycles at 1 A g^(-1). The two-step discharging process, namely a consequent H^(+) and Mg^(2+) insertion reaction, is verified, by comparing the electrochemical performance of δ-MnO_(2) in 1 M MgCl_(2) and 1 M MnCl_(2) aqueous electrolyte and analyzing detailedly the Mg content and the bonding state of Mn at different charge/discharge state. Furthermore, partial irreversibility of Mg^(-1) ion insertion/extraction is observed, which may be one of the major reasons leading to capacity decay.

一种航空发动机风扇叶片的强度分析

航空发动机是一种具有严格气动负荷、机械负荷,且要求强耐久性的热动力机械,它是由许多零部件和附件组成的复杂系统,其可靠性和寿命直接影响着飞行的安全性,而航空发动机的寿命,很大程度上取决于主要零部件的寿命。本文对国内B737民航班机CFM56发动机的风扇叶片的强度展开了一系列研究,为提高发动机可靠性提供了参考价值。利用CATIA自带的有限元软件建立了发动机风扇的有限元模型,分别计算了风扇在不同转速下的离心应力分布和不同转速下扭矩对风扇的影响,并对其静强度进行了强度校核。

Development and Validation of an LC-MS/MS Method for Determination of Catalpol and Harpagide in Small Volume Rat Plasma: Application to a Pharmacokinetic Study

A rapid and sensitive liquid chromatography-tandem mass chromatography (LC-MS/MS) method has been developed and validated for simultaneous determination of catalpol and harpagide in rat plasma. The samples were extracted by one-step protein precipitation and separated on a SunFireTM C18 column (100 mm × 2.1 mm, 3.5 &mu;m;Waters) using acetonitrile-10 mM ammonium formate as mobile phase at a flow rate 0.3 mL/min in gradient mode. The analytes were detected without interference in Multiple Reaction Monitoring (MRM) mode with negative electrospray ionization. Linear responses were obtained for catalpol ranging from 20 to 5000 ng/mL and harpagide ranging from 10 to 2500 ng/mL. Coefficients of correlation (r) for the calibration curves were more than 0.99 for both analytes. Intra- and inter-day accuracy and precision were within the acceptable limits of less than 15.0% at all concentrations. The quantitation method was successfully applied for simultaneous estimation of catalpol and harpagide after oral administration of Zeng Ye Decoction.

Scaling Factor Optimization of Turbo-Polar Iterative Decoding

In this paper, we investigate the weighted iterative decoding to improve the performance of turbo-polar code. First of all, a minimum weighted mean square error criterion is proposed to optimize the scaling factors(SFs). Secondly, for two typical iterative algorithms,such as soft cancellation(SCAN) and belief propagation(BP) decoding, genie-aided decoders are proposed as the ideal reference of the practical decoding. Guided by this optimization framework, the optimal SFs of SCAN or BP decoders are obtained. The bit error rate performance of turbo-polar code with the optimal SFs can achieve 0.3 dB or 0.7 dB performance gains over the standard SCAN or BP decoding respectively.

Degradation kinetics of larotaxel and identification of its degradation products in alkaline condition

Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH（1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0） and temperature（0, 25, 37 and 45 °C）. The linear range was 0.5–25 μg/mL, the intra-and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 k J/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.

Changes in corneal curvature and aberrations after cataract surgery

Background:Surgically induced astigmatism(SIA)and corneal high-order aberrations(HOAs)are the two main causes of poor visual quality after cataract surgery.Changes in the parameters of corneal HOAs after cataract surgery and their effects on and relationships with changes in corneal curvature have not yet been reported.This study aimed to explore changes in anterior,posterior and total corneal curvature,astigmatism and HOAs after microincision cataract surgery.Methods:Sixty-one age-related cataract patients(61 eyes)were included in this prospective study.The total,anterior and posterior corneal astigmatism and corneal HOAs were analyzed by anterior segment optical coherence tomography(AS-OCT)and iTrace before,one day,one week and three months after 2.2 mm temporal microincision coaxial phacoemulsification to evaluate the changes in anterior,posterior and total corneal curvature,astigmatism and corneal HOAs.Results:The mean J0 and J45 values of anterior,posterior and total corneal curvature obtained by ASOCT showed no statistically significant difference between preoperatively and any postoperative followup.SIA occurred on the anterior,posterior and total corneal surfaces and showed no statistically significant difference at any postoperative follow-up.No significant changes in 3rd-order oblique trefoil,vertical coma or 4th-order spherical aberrations were observed after surgery except for a significant increase in horizontal coma at postoperative day 1(POD1).Conclusions:There were no significant changes in corneal curvature after 2.2 mm temporal microincision coaxial phacoemulsification,and the corneal HOAs were not changed significantly except for the increase in horizontal coma at POD1,which may be one of the main reasons of poor visual quality at POD1 in some cataract patients who have good uncorrected or corrected distance vision.

Changes in crystalline lens parameters during accommodation evaluated using swept source anterior segment optical coherence tomography

Backgrounds:To assess changes in anterior segment biometry during accommodation using a swept source anterior segment optical coherence tomography(SS-OCT).Methods:One hundred-forty participants were consecutively recruited in the current study.Each participant underwent SS-OCT scanning at 0 and−3 diopter(D)accommodative stress after refractive compensation,and ocular parameters including anterior chamber depth(ACD),anterior and posterior lens curvature,lens thickness(LT)and lens diameter were recorded.Anterior segment length(ASL)was defined as ACD plus LT.Lens central point(LCP)was defined as ACD plus half of the LT.The accommodative response was calculated as changes in total optical power during accommodation.Results:Compared to non-accommodative status,ACD(2.952±0.402 vs.2.904±0.382 mm,P<0.001),anterior(10.771±1.801 vs.10.086±1.571 mm,P<0.001)and posterior lens curvature(5.894±0.435 vs.5.767±0.420 mm,P<0.001),lens diameter(9.829±0.338 vs.9.695±0.358 mm,P<0.001)and LCP(4.925±0.274 vs.4.900±0.259 mm,P=0.010)tended to decreased and LT thickened(9.829±0.338 vs.9.695±0.358 mm,P<0.001),while ASL(6.903±0.279 vs.6.898±0.268 mm,P=0.568)did not change significantly during accommodation.Younger age(β=0.029,95%CI:0.020 to 0.038,P<0.001)and larger anterior lens curvature(β=−0.071,95%CI:−0.138 to−0.003,P=0.040)were associated with accommodation induced greater steeping amplitude of anterior lens curvature.The optical eye power at 0 and−3 D accommodative stress was 62.486±2.284 and 63.274±2.290 D,respectively(P<0.001).Age was an independent factor of accommodative response(β=−0.027,95%CI:−0.038 to−0.016,P<0.001).Conclusions:During−3 D accommodative stress,the anterior and posterior lens curvature steepened,followed by thickened LT,fronted LCP and shallowed ACD.The accommodative response of−3 D stimulus is age-dependent.

A Study on Investment Structure of Fixed Assets and Regional Economic Growth

Nowadays,it has been in the period of rapidly developing China’s economy.Since the financial crisis in 2008,China has paid more and more attention to investing in fixed assets,and the growth rate of investing in fixed asset is also rising.However,when promoting regional economic growth,if we only pay attention to the total amount of fixed asset investment,there will inevitably exist some blindness and lack of sustainability.Therefore,the study between the investment structure of fixed assets and regional economic growth is quite important.China has a vast territory and many regions.The investment structure of fixed assets in different regions is also different,so the influence on economic growth is also different.This paper analyzes the investment structure of fixed assets and regional economic growth,and help realize the rapid growth of regional economy by recognizing the current situation of China's investment structure of fixed assets.

Targeted axillary dissection after neoadjuvant chemotherapy for highly selective patients with initial cN1 breast cancer:A single-center prospective trial

Background:Sentinel lymph node(SLN)biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy(NAC).However,it is still difficult to precisely define pre-NAC clinical node-positive(cN1)and post-NAC clinical node-negative(ycN0).This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection(TAD)after NAC in highly selective pre-NAC cN1 patients(not considering ultrasound-based axillary ycN staging).Methods:This prospective trial included patients with initial pre-NAC cT1-3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University.When NAC was effective(including complete and partial responses)and preoperative axillary palpation was negative,preoperative ultrasound-based axillary staging was not considered,and all patients underwent TAD followed by axillary lymph node(LN)dissection.The detection rate(DR)and false-negative rate(FNR)of TAD were calculated.Results:A total of 82 patients were included,and 77 of them were eligible for data analysis.The DR for TAD was 94.8%(73/77).There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound,45 patients with two,and 2 patients with three.One patient had one TAD LN,four patients had two TAD LNs,and 68 patients had three or more TAD LNs.Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD.Preoperative ultrasound-based ycN0 and ycN+conditions were detected for 52 and 21 cases,respectively.The FNR was 7.4%(2/27)for standard TAD(≥3 SLNs),which was lower than that of all successful TAD(≥1 SLN;10.0%,3/30).Conclusions:In rigorously defined pre-NAC cN1 breast cancer patients,standard TAD is feasible for those with negative axillary palpation after NAC,and FNR is also less than 10%.Registration:chictr.org.cn,ChiCTR2100049093.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer:an interim analysis of a phase Ⅲ randomized clinical trial

Background:In the era of immunotherapy,neoadjuvant immunochemotherapy(NAIC)for the treatment of locally advanced esophageal squamous cell carcinoma(ESCC)is used clinically but lacks of high-level clinical evidence.This study aimed to compare the safety and long-term efficacy of NAIC followed byminimally invasive esophagectomy(MIE)with those of neoadjuvant chemotherapy(NAC)followed by MIE.Methods:A prospective,single-center,open-label,randomized phase Ⅲ clinical trial was conducted at Henan Cancer Hospital,Zhengzhou,China.Patients were randomly assigned to receive either neoadjuvant toripalimab(240mg)plus paclitaxel(175 mg/m^(2))+cisplatin(75 mg/m^(2))(toripalimab group)or paclitaxel+cisplatin alone(chemotherapy group)every 3 weeks for 2 cycles.After surgery,the toripalimab group received toripalimab(240 mg every 3 weeks for up to 6 months).The primary endpoint was event-free survival(EFS).The pathological complete response(pCR)and overall survival(OS)were key secondary endpoints.Adverse events(AEs)and quality of life were also assessed.Results:Between May 15,2020 and August 13,2021,252 ESCC patients ranging fromT1N1-3M0 to T2-3N0-3M0were enrolled for interim analysis,with 127 in the toripalimab group and 125 in the chemotherapy group.The 1-year EFS rate was 77.9%in the toripalimab group compared to 64.3%in the chemotherapy group(hazard ratio[HR]=0.62;95%confidence interval[CI]=0.39 to 1.00;P=0.05).The 1-year OS rates were 94.1%and 83.0%in the toripalimab and chemotherapy groups,respectively(HR=0.48;95%CI=0.24 to 0.97;P=0.037).The patients in the toripalimab group had a higher pCR rate(18.6%vs.4.6%;P=0.001).The rates of postoperative Clavien-Dindo grade Ⅲb or higher morbidity were 9.8%in the toripalimab group and 6.8%in the chemotherapy group,with no significant difference observed(P=0.460).The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups(12.5%versus 12.4%).Conclusions:The interim results of this ongoing trial showed that in resectable ESCC,the addition of perioperative toripalimab to NAC is safe,may improve OS and might change the standard treatment in the future.