Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

辐射活性接枝聚合制备双重响应性还原氧化石墨烯材料

本研究通过辐射可逆加成?断裂链转移聚合在氧化石墨烯(GO)表面接枝了具有温度响应性的聚(N-异丙基丙烯酰胺)(PNIPAAm)。Raman光谱和X射线光电子能谱分析表明,GO在水溶液中共辐射接枝时会被同步还原。吸收剂量为1.8~14.4 kGy时,接枝了PNIPAAm的还原氧化石墨烯(rGO-g-PNIPAAm)还原程度和接枝率均随吸收剂量而增加。脉冲辐解研究证明,NIPAAm与水辐解产生的水合电子(e_(aq)^(-))和羟基自由基(OH)均会反应,反应速率常数分别为1.0×10^(10)L/(mol·s)和(4.3±0.2)×10^(9) L/(mol·s)。NIPAAm与OH反应在不饱和双键位置形成自由基,引发单体自由基加成聚合。而NIPAAm与e_(aq)^(-)的反应,不仅消耗了强还原性的e_(aq)^(-),还生成了还原性较弱的阴离子自由基中间产物,从而降低了r GO的还原程度。低还原程度的rGO表面残余羧基等含氧基团,赋予了rGO-g-PNIPAAm良好的p H响应性。辐射接枝的吸收剂量为3.6 kGy时,所制备的rGO-g-PNIPAAm具有优异的光热转换性能,较未接枝改性的GO提升30%。本工作为制备具有pH和温度双重响应性的光热转换材料提供了便捷、可控的方法。

Evaluation of bacterial contamination and medium-term oncological outcomes of intracorporeal anastomosis for colon cancer:A propensity score matching analysis

BACKGROUND Although intracorporeal anastomosis(IA)for colon cancer requires longer operative time than extracorporeal anastomosis(EA),its short-term postoperative results,such as early recovery of bowel movement,have been reported to be equal or better.As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum,there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells.However,intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified.abdominal cavity in IA.METHODS Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020,75 underwent EA(EA group),and 52 underwent IA(IA group).After propensity score matching,the primary endpoint was 3-year disease-free survival rates,and secondary endpoints were 3-year overall survival rates,type of recurrence,surgical site infection(SSI)incidence,number of days on antibiotics,and postoperative biological responses.RESULTS Three-year disease-free survival rates did not significantly differ between the IA and EA groups(87.2%and 82.7%,respectively,P=0.4473).The 3-year overall survival rates also did not significantly differ between the IA and EA groups(94.7%and 94.7%,respectively;P=0.9891).There was no difference in the type of recurrence between the two groups.In addition,there were no significant differences in SSI incidence or the number of days on antibiotics;however,postoperative biological responses,such as the white blood cell count(10200 vs 8650/mm^(3),P=0.0068),C-reactive protein(6.8 vs 4.5 mg/dL,P=0.0011),and body temperature(37.7 vs 37.5℃,P=0.0079),were significantly higher in the IA group.CONCLUSION IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

Low-Energy Spin Excitations in Detwinned FeSe

Antiferromagnetic spin fluctuation is regarded as the leading driving force for electron pairing in high-Tc superconductors.In iron-based superconductors,spin excitations at low energy range,especially the spin-resonance mode at ER~5kBTc,are important for understanding the superconductivity.Here,we use inelastic neutron scattering(INS)to investigate the symmetry and in-plane wave-vector dependence of low-energy spin excitations in uniaxial-strain detwinned Fe Se.The low-energy spin excitations(E<10 meV)appear mainly at Q=(±1,0)in the superconducting state(T9K)and the nematic state(T90 K),confirming the constant C_(2) rotational symmetry and ruling out the C_(4) mode at E≈3 meV reported in a prior INS study.Moreover,our results reveal an isotropic spin resonance in the superconducting state,which is consistent with the s±wave pairing symmetry.At slightly higher energy,low-energy spin excitations become highly anisotropic.The full width at half maximum of spin excitations is elongated along the transverse direction.The Q-space isotropic spin resonance and highly anisotropic low-energy spin excitations could arise from dyz intra-orbital selective Fermi surface nesting between the hole pocket aroundΓpoint and the electron pockets centered at MX point.

Establishment of a surveillance program for anal cancer in Crohn's disease

This letter discusses the incidence of anal cancer among Crohn's disease(CD)-related malignancies.Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals.Although CD-associated anal cancer is relatively rare,patients with CD accom-panied by anal or perianal lesions are at increased risk of anal cancer.Addi-tionally,compared to ulcerative colitis,which is also an inflammatory disease,CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences.Therefore,the detection of early-stage cancer is crucial for improving the prognosis.However,the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis.They are not appropriate for detecting CD-related malignancies in the recto-anal region.Therefore,there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

专为电动汽车市场的轮胎和橡胶制品设计的炭黑

本文探讨了特种炭黑材料EV 800在电动汽车轮胎和橡胶制品中的应用。EV 800具有可持续性、高结构和适宜的表面积,且已通过ISCC Plus认证,它能增强轮胎强度和耐久性,减少滚动阻力,提升电动汽车的能效。本文总结了EV 800对轮胎性能的积极影响,并通过实验对比确认了其作为电动汽车轮胎材料的适宜性,强调了其强度、能效提升和可持续性特点。

Accuracy and Utility of Vessel Analysis Using Non-Contrast CT for Planning Endovascular Aortic Repair

Objectives: This study aimed to determine whether errors in vascular measurements would affect device selection in endovascular aortic repair (EVAR) by comparing measurements obtained using non-contrast computed tomography (NCT) with those obtained using contrast-enhanced CT (CECT). Materials and Methods: This single-center, retrospective study included 25 patients who underwent EVAR for abdominal aortic aneurysm at our institution. A 1-mm horizontal cross-sectional slice of NCT and CECT from each patient was retrospectively reviewed. The area from the abdominal aorta to the common iliac artery was divided into four zones. A centerline was created using the NCT by manually plotting the center points. Subsequently, the centerlines were automatically extracted and manually corrected during the arterial phase of CECT. The diameter and length of each zone were measured for each modality. The mean diameters and lengths of the target vessels were compared between NCT and CECT. Results: The measurements obtained using both methods were reproducible and demonstrated good agreement. The mean differences in vessel length and diameter measurements for each segment between NCT and CECT were not statistically significant, indicating good consistency. Conclusion: NCT may be useful for preoperative EVAR evaluation in patients with renal dysfunction or allergies to contrast agents.

天然人源IgG Fab噬菌体抗体库的构建及多样性分析

目的:构建天然人源IgGFab噬菌体抗体库并分析来源于健康人外周血B淋巴细胞的抗体基因可变区的多样性及优势选择。方法:以DNA重组技术从300名健康志愿者的外周血淋巴细胞中扩增出全套人抗体轻链及重链Fd基因,分别插入噬菌体载体pFabICN相应位置,构建天然人源免疫球蛋白G基因文库;进一步从抗体库中随机挑选克隆,获得重轻链基因进行核苷酸序列测定并利用IgBLAST数据库分析抗体基因可变区的同源家族。结果:从4×108库容的天然人源IgGFab噬菌体抗体库中随机挑选克隆,对其中32个轻链及重链Fd基因插入正确的克隆进行核苷酸序列测定和氨基酸序列的推算,获得29条彼此完全不同的Fd重链基因及轻链基因。以IgBLAST数据库比对分析显示29条重链基因的V区分别属于VH3(72.4%),VH1(10.3%),VH4(6.9%),VH5(6.9%)和VH7(3.4%)基因家族。29条轻链基因分别属于Vκ1(44.8%),Vκ2(15.4%),Vκ3(11.5%),Vκ4(23.1%)基因家族和Vλ1(11.5%)基因家族。结论:以300份健康人外周血淋巴细胞的抗体基因构建的天然人源IgGFab噬菌体抗体库基因多样性良好,重链VH3基因家族存在优势表达。

基于六角形和球形冰晶模型的卷云辐射特征研究

卷云中冰晶粒子的单次光散射计算是卷云辐射传输及云微物理参数反演的重要基础。近年,利用高观测频率的静止气象卫星数据来反演水云和卷云的光学和微物理参数,进而计算地表光通量的研究倍受重视。然而,很多研究中卷云的冰晶用球形模型来模拟。由于不同形状和尺度大小的冰晶对电磁波的散射特征的不同,导致不同冰晶模型计算的卷云环境下卫星观测的辐射值及地表光通量的不同。利用不同尺度大小和电磁波波长的球形和六角形冰晶的单次散射数据,结合RSTAR辐射传输模式来定量分析了卷云环境下不同形状的冰晶模型对计算卫星观测的辐射和地表光通量中的影响。结果显示利用不同形状的冰晶模块来计算的卫星观测的辐射,地表向下辐射通量明显不同。波长在0.4～1.0μm之间的大气窗口部分的光谱辐射通量的差距最大。总辐射通量受云粒子形状的影响显著。研究证实了正确选择冰晶模型对卫星反演卷云微物理和光学参数的反演及计算地表光通量的重要性。该结果对于云微物理参数的反演及地表向下辐射通量的模拟具有参考价值。

多聚酶链反应分析溶组织内阿米巴的致病性

从急性阿米巴痢疾患者粪便中分离所得的溶组织内阿米巴虫株SH-3、SH-6、SH-8的DNA和包囊携带者粪便中分离所得的溶组织内阿米巴 SH-5、SH-7的 DNA应用多聚酶链反应技术扩增30个周期后作琼脂糖凝胶电泳分析,发现致病性引物 P_(11)、P_(12)可使SH-8虫株的DNA增殖;而非致病性引物P_(13)、P_(14)可使SH-3、SH-5、SH-6和SH-7虫株的DNA增殖。另外,酶株群分析和单克隆抗体反应也显示SH-8为致病性虫株,而另4株虫株均属于非致病性虫株,与多聚酶链反应的结果相一致。提示,致病性虫株与非致病性虫株的基因有区别,多聚酶链反应对溶组织内阿米巴进行基因分析是一种敏感和特异的新方法。

双奇核^(172)Re高自旋态实验研究

利用149Sm(27Al,4nγ)172Re反应布居了形变双奇核172Re的高自旋态,用12套带有BGO反康普顿抑制的高纯锗探测器阵列进行了在束γ实验测量,首次建立了172Re由3个转动带构成的高自旋态能级纲图.研究和讨论了3个转动带的结构特征,基于已有的高自旋态核结构知识并通过系统学比较和分析指出它们的准粒子组态分别为πh11/2 νi13/2,πh9/2 νi13/2和 π1/2-[541] ν1/2-[521].发现前两个转动带在自旋小于18时其转动能级呈现反常的旋称劈裂.

Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review

Spontaneous bacterial(SBP) and spontaneous fungal peritonitis(SFP) can be a life-threatening infection in patients with liver cirrhosis(LC) and ascites. One of the possible mechanisms of developing SBP is bacterial translocation. Although the number of polymorphonuclear cells in the culture of ascitic fluid is diagnostic for SBP, secondary bacterial peritonitis is necessary to exclude. The severity of underlying liver dysfunction is predictive of developing SBP; moreover, renal impairment and infections caused by multidrug-resistant(MDR) organism are associated with a fatal prognosis of SBP. SBP is treated by antimicrobials, but initial empirical treatment may not succeed because of the presence of MDR organisms, particularly in nosocomial infections. Antibiotic prophylaxis is recommended for patients with LC at a high risk of developing SBP, gastrointestinal bleeding, or a previous episode of SBP, but the increase in the risk of developing an infection caused by MDR organisms is a serious concern globally. Less is known about SFP in patients with LC, but the severity of underlying liver dysfunction may increase the hospital mortality. SFP mortality has been reported to be higher than that of SBP partially because the difficulty of early differentiation between SFP and SBP induces delayed antifungal therapy for SFP.

Evaluation and treatment of malignant ascites secondary to gastric cancer

Malignant ascites affects approximately 10% of patients with gastric cancer(gC), and poses significant difficulties for both patients and clinicians. In addition to the dismal general condition of affected patients and the diversity of associated complications such as jaundice and ileus, problems in assessing scattered tumors have hampered the expansion of clinical trials for this condition. However, the accumulation of reported studies is starting to indicate that the weak response to treatment in g C patients with malignant ascites is more relevant to their poor prognosis rather than to the ascites volume at diagnosis. Therefore, precise assessment of initial state of ascites, repetitive evaluation of treatment efficacy, selection of suitable treatment, and swift transition to other treatment options as needed are paramount to maximizing patient benefit. Accurately determining ascites volume is the crucial first step in clinically treating a patient with malignant ascites. Ultrasonography is commonly used to identify the existence of ascites, and several methods have been proposed to estimate ascites volume. Reportedly, the sum of the depth of ascites at five points(named "five-point method") on three panels of computed tomography images is well correlated to the actual ascites volume and/or abdominal girth. This method is already suited to repetitive assessment due to its convenience compared to the conventional volume rendering method. Meanwhile, a new concept, "Clinical Benefit Response in g C(CBR-GC)", was recently introduced to measure the efficacy of chemotherapy for malignant ascites of g C. CBR-GC is a simple and reliable patient-oriented evaluation system based on changes in performance status and ascites, and is expected to become an important clinical endpoint in future clinical trials. The principal of treatment for g C patients with ascites is palliation and prevention of ascites-related symptoms. The treatment options are various, including a standard treatment based on the available guidelines, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(HIPEC), laparoscopic HIPEC alone, intravenous chemotherapy, intraperitoneal chemotherapy, and molecular targetingtherapy. Although each treatment option is valid,further research is imperative to establish the optima choice for each patient.

Effect of in vitro interferon-beta administration on hepatitis C virus in peripheral blood mononuclear cells as a predictive marker of clinical response to interferon treatment for chronic hepatitis C

AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P<0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.

Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant

We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.

Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double-blind, placebo-controlled study

AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM(group I) or rabeprazole plus placebo(group P).The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease(FSSG) and the short form(SF)-36 quality of life questionnaires after four weeks of treatment.We also assessed whether patients with NERD with minimal changes(grade M) had different responses to the therapies compared with patients who did not have minimal changes(grade N).RESULTS:Group I and group P showed significant improvements in their FSSG scores after the treatment(from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P.Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N(modified Los Angeles classification)(7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041).The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.CONCLUSION:The addition of IM to rabeprazole significantly improves gastroesophageal reflux diseasesymptoms and the quality of the lives of patients with NERD grade N.

Function-preserving gastrectomy for gastric cancer in Japan

Surgery used to be the only therapy for gastric cancer, and since its ability to cure gastric cancer was the focus of attention, less attention was paid to functionpreserving surgery in gastric cancer, though it was studied for gastroduodenal ulcer. Maki et al developed pylorus-preserving gastrectomy for gastric ulcer in 1967. At the same time, the definition of early gastric cancer(EGC) was being considered, histopathological investigations of EGC were carried out, and the validity of modified surgery was sustained. After the development of H2-blockers, the number of operations for gastroduodenal ulcers decreased, and the number of EGC patients increased simultaneously. As a result, the indications for pylorus-preserving gastrectomy for EGC in the middle third of the stomach extended, and various alterations were added. Since then, many kinds of function-preserving gastrectomies have been performed and studied in other fields of gastric cancer, and proximal gastrectomy, jejunal pouch interposition, segmental gastrectomy, and local resection have been performed. On the other hand, from the overall perspective, it can be said that endoscopic resection, which was launched at almost the same time, is the ultimate function-preserving surgery under the current circumstances. The current function-preserving gastrectomies that are often performed and studied are pylorus-preserving gastrectomy and proximal gastrectomy. The reasons for this are that these procedures that can be performed with systemic lymph node dissection, and they include three important elements:(1) reduction of the extent of gastrectomy;(2) preservation of the pylorus; and(3) preservation of the vagal nerve. In addition, these operations are more likely to be performed with a laparoscopic approach as minimally invasive surgery. Of the above-mentioned three elements, reduction of the extent of gastrectomy is the most important in our view. Therefore, we should try to reduce the extent of gastrectomy if curability of the gastric cancer can still be achieved. However, if we preserve a wider residual stomach in functionpreserving gastrectomy, we should pay attention to the development of metachronous gastric cancer.

Risk factors for proximal migration of biliary tube stents

AIM: To analyze the risk factors for biliary stent migration in patients with benign and malignant strictures.

Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs > G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of > G2 skin toxicity,and absence of > G2 hypoalbuminemia.The disease control rate in patients with > G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and > G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.

Role of stereotactic body radiation therapy for hepatocellular carcinoma

The integration of new technologies has raised an interest in liver tumor radiotherapy,with literature evolving to support its efficacy.These advances,particularly stereotactic body radiation therapy(SBRT),have been critical in improving local control or potential cure in liver lesions not amenable to first-line surgical resection or radiofrequency ablation.Active investigation of SBRT,particularly for hepatocellular carcinoma(HCC),has recently started,yielding promising local control rates.In addition,data suggest a possibility that SBRT can be an alternative option for HCC unfit for other local therapies.However,information on optimal treatment indications,doses,and methods remains limited.In HCC,significant differences in patient characteristics and treatment availability exist by country.In addition,the prognosis of HCC is greatly influenced by underlying liver dysfunction and treatment itself in addition to tumor stage.Since they are closely linked to treatment approach,it is important to understand these differences in interpreting outcomes from various reports.Further studies are required to validate and maximize the efficacy of SBRT by a large,multi-institutional setting.