Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

Protective performance of shear stiffening gel-modified foam against ballistic impact:Experimental and numerical study

As one of the most widely used personal protective equipment(PPE),body armors play an important role in protecting the human body from the high-velocity impact of bullets or projectiles.The body torso and critical organs of the wear may suffer severe behind-armor blunt trauma(BABT)even though the impactor is stopped by the body armor.A type of novel composite material through incorporating shear stiffening gel(STG)into ethylene-vinyl acetate(EVA)foam is developed and used as buffer layers to reduce BABT.In this paper,the protective performance of body armors composed of fabric bulletproof layers and a buffer layer made of foam material is investigated both experimentally and numerically.The effectiveness of STG-modified EVA in damage relief is verified by ballistic tests.In parallel with the experimental study,numerical simulations are conducted by LS-DYNA®to investigate the dynamic response of each component and capture the key mechanical parameters,which are hardly obtained from field tests.To fully describe the material behavior under the transient impact,the selected constitutive models take the failure and strain rate effect into consideration.A good agreement between the experimental observations and numerical results is achieved to prove the validity of the modelling method.The tests and simulations show that the impact-induced deformation on the human body is significantly reduced by using STG-modified EVA as the buffering material.The improvement of protective performance is attributed to better dynamic properties and more outstanding energy absorption capability of the composite foam.

Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis:Implications for bone health

BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Intestinal barrier in inflammatory bowel disease:A bibliometric analysis

The primary objective of this investigation was to examine the evolving trajectories and pivotal focal points within the domain of research on intestinal barriers with regard to inflammatory bowel disease(IBD).Publications germane to the intestinal barrier in the context of IBD were procured from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric scrutiny and visualization were executed employing the R package"bibliometrix"through the R software platform(version:4.3.0).A comprehensive compilation of 7344 English-language articles spanning from January 1,2001 to December 31,2021 was meticulously identified and included in the analysis.Remarkably,China emerged as the preeminent force in the realm of intestinal barrier research in relation to IBD.The significance of the intestinal barrier in the context of IBD has been progressively and comprehensively acknowledged.This recognition has ushered in a fresh therapeutic perspective that offers the promise of enhancing the management of inflammation and prognostication.

2D/3D钙钛矿异质结中多重量子阱的形成使声子瓶颈效应失效

声子瓶颈效应对有机-无机杂化钙钛矿光电性能的重要性已经广为认知.虽然在2D/3D异质结构中经常产生随机分布的多重量子阱结构,但人们对2D/3D钙钛矿异质结构中多重量子阱的形成对声子瓶颈效应的影响知之甚少.本文使用2D有机-无机杂化钙钛矿(NH_(3)(CH_(2))_(8)NH_(3)PbI_(4))去钝化3D有机-无机杂化钙钛矿,构建了2D/3D钙钛矿异质结构,并通过光致发光光谱和飞秒光泵浦太赫兹探测光谱研究了其激子和载流子动力学.观察到了多重量子阱结构的形成,并建立了激子形成时间、热载流子冷却速率和有效电荷载流子迁移率之间的结构-动力学-性能的构效关系.多重量子阱结构的形成可使声子瓶颈效应失效,并且调控2D/3D钙钛矿异质结的光电性能.该工作为构建2D/3D钙钛矿异质结构策略中认识能带排列和声子瓶颈效应的重要性提供有价值的信息.

A High-Randomness and High-Stability Electronic Quantum Random Number Generator without Post Processing

Random numbers are one of the key foundations of cryptography.This work implements a discrete quantum random number generator(QRNG)based on the tunneling effect of electrons in an avalanche photo diode.Without any post-processing and conditioning,this QRNG can output raw sequences at a rate of 100 Mbps.Remarkably,the statistical min-entropy of the 8,000,000 bits sequence reaches 0.9944 bits/bit,and the min-entropy validated by NIST SP 800-90B reaches 0.9872 bits/bit.This metric is currently the highest value we have investigated for QRNG raw sequences.Moreover,this QRNG can continuously and stably output raw sequences with high randomness over extended periods.The system produced a continuous output of 1,174 Gbits raw sequence for a duration of 11,744 s,with every 8 Mbits forming a unit to obtain a statistical min-entropy distribution with an average value of 0.9892 bits/bit.The statistical min-entropy of all data(1,174 Gbits)achieves the value of0.9951 bits/bit.This QRNG can produce high-quality raw sequences with good randomness and stability.It has the potential to meet the high demand in cryptography for random numbers with high quality.

Laparoscopic pancreaticoduodenectomy: From “standard” to “extended”

Pancreatic cancer is one of the most desperate malignances worldwide with approximately 470 0 0 0 deaths per year, and the 5-year survival rate is only 11% [1]. Pancreaticoduodenectomy(PD) is the standard treatment for pancreatic head and periampullary lesions [2]. PD is often either described as “standard PD” or “extended PD”(e.g., “PD with portal vein resection, additional organ resection or arterial resection”) [3].

Hepatic arterial anastomosis in adult liver transplantation

Hepatic arterial reconstruction remains a critically challenging technique in liver transplantation,as efficient graft and patient survival are dependent on strong and continuous arterial blood supply to the donor liver[1,2].Complex arterial reconstruction has been identified as a crucial risk factor for arterial thrombosis[1–5].Consequently,selecting the appropriate arterial reconstruction method to decrease hepatic artery thrombosis has garnered the attention of the surgical community.

Immune checkpoint inhibitor for hepatocellular carcinoma recurrence after liver transplantation

To the Editor:Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally.Hepatocellular carcinoma(HCC)accounts for 90%of primary liver cancers with the highest incidence in China(more than 50%of all cases worldwide)[1].Liver transplantation(LT)is regarded as an optimal therapy for selected HCC patients.The Milan criteria are the benchmark for candidate selection that ensure excellent prognosis for patients with HCC[2].The Hangzhou criteria expand 51.5%more of Milan criteria for LT candidates with comparable posttransplant survivals[3].However,LT recipients fulfilling Milan criteria or Hangzhou criteria are at the risk of up to 13%−18%HCC recurrence rate within five years[4].Only 25%−50%of recurrent HCC patients post-LT are eligible for surgical treatment which have consistently presented favored survival benefit than systemic therapy[5].

乳腺癌组织中趋化因子CXCL3的表达意义

目的:研究乳腺癌组织中趋化因子CXCL3的表达,探讨CXCL3表达与乳腺癌临床病理参数的相关性。方法:利用免疫组织化学方法检测乳腺癌组织中CXCL3的表达情况。结果:CXCL3的表达量与乳腺癌患者的年龄,肿瘤大小及是否有无淋巴结转移不具有相关性(P>0.05),而Ⅲ级乳腺癌组织中CXCL3的表达量明显高于Ⅱ级乳腺癌组织(P=0.000)。结论:CXCL3表达水平与乳腺癌临床病理分级呈正相关,其可能参与乳腺癌发生与演进过程。

细胞信号转导通路与肝癌相关性研究进展

细胞信号转导是指信号分子通过刺激胞膜或者胞内受体,引起细胞内发生信号转导,从而影响细胞生物学功能的过程.近年来研究发现,某些细胞信号转导通路的激活或者抑制在肝癌(hepatocellular carcinoma,HCC)细胞的发生、发展中起着重要推动作用.本文将对近年来有关HCC的热门细胞信号转导通路的研究进行综述.

原发性肝癌分子靶向治疗基础与临床研究进展

原发性肝癌是世界上发病率第2的癌症,已成为我国癌症相关死亡原因中最常见的原因之一,对病人及患者家庭带来巨大的病痛和经济负担.传统的治疗方法迄今并未取得令人满意的效果,人们逐渐将目光转向有着精确性、不良反应小等诸多优点的靶向药物治疗.已有研究证实靶向药物索拉非尼的上市能改善原发性肝癌患者生存期,开启肿瘤靶向治疗的新纪元,近年来,肝癌的分子靶向治疗成为研究热点,随着研究的深入,已发现多种新型分子靶向药物能改善中晚期肝癌患者的预后.本文旨在阐述原发性肝癌分子靶向治疗基础与临床研究的最新进展.

原发性肝癌靶向药物治疗试验与临床研究进展

肝癌是一种高发的消化系统恶性肿瘤,传统的治疗方法对于中晚期肝癌疗效不佳,索拉非尼是第一个用于肝癌治疗的分子靶向药物,靶向药物的出现为中晚期肝癌患者提供了新的选择.近年来,特别是免疫治疗的加入,已发现许多新型靶向药物可明显改善中晚期肝癌患者的预后,因此靶向药物成为了研究热点.本文就近年来肝癌靶向药物治疗试验及临床研究进展做一综述.

Heterotopic pancreas in the gastrointestinal tract

Heterotopic pancreas is defined as pancreatic tissue found outside the usual anatomical location of the pancreas. It is often an incidental finding and can be found at different sites in the gastrointestinal tract. It may become clinically evident when complicated by pathological changes such as inflammation, bleeding, obstruction, and malignant transformation. In this report, a 60-year-old man with carcinoid syndrome caused by heterotopic pancreatic tissue in the duodenum is described, along with a 62-year-old man with abdominal pain caused by heterotopic pancreatic tissue in the gastric antrum. The difficulty of making an accurate diagnosis is highlighted. The patients remain healthy and symptom-free after follow-up of 1 year. Frozen sections may help in deciding the extent of resection intraoperatively. Although heterotopic pancreas is rare, it should be considered in the differential diagnosis of gastrointestinal stromal tumor.

Impact of treatment modalities on patients with recurrent hepatocellular carcinoma after liver transplantation:Preliminary experience

Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.

Clinical practice guidelines on liver transplantation for hepatocellular carcinoma in China(2018 edition)

Introduction Over 300000 people in China die each year of hepatocellular carcinoma(HCC),which accounts for approximately half of HCCrelated deaths worldwide.Liver transplantation(LT)is generally recognized as one of the most effective therapeutic approaches for end-stage liver diseases.Since the beginning of the second LT boom in the 1990s,LT in China has been developed rapidly with professional and large-scale trends,and it is approaching or has reached the level of developed countries in terms of quantity and quality.According to the China Liver Transplant Registry,the number of transplants for HCC accounted for 36.8%of the total number of LT cases during the past 5 years in the mainland of China.In order to develop an effective,safe and standardized protocol to guide the national LT practice,the clinical guidelines of LT for HCC was launched in 2014 by multidisciplinary experts from Chinese Society of Organ Transplantation,Chinese Medical Association and Chinese Association of Organ Transplantation,Chinese Medical Doctor Association.Recently,there have been new clinical and scientific advances in the field of LT and to keep abreast of these achievements,the original clinical practice guidelines need to be updated.

Hepatitis B virus X protein enhances hepatocarcinogenesis by depressing the targeting of NUSAP1 mRNA by miR-18b

Objective: The aim of this study was to investigate the underlying mechanism whereby HBx modulates the targeting of NUSAP1 by miR-18b to enhance hepatocarcinogenesis.Methods: We employed an integrated approach of bioinformatics analysis and molecular experiments in hepatoma cells, HBV transgenic mice, and clinical liver cancer tissues to investigate the role of HBx-regulated miR-18b in the development of liver cancer.Results: In this study, we report that the HBx-mediated tumor suppressor miR-18b modulates hepatocarcinogenesis during the host-HBV interaction. The expression levels of miR-18b were lower in clinical HBV-positive liver cancer tissues and liver tissues of HBV-transgenic mice. Interestingly, HBx inhibited miR-18b expression by inducing the methylation of CpG islands in its promoter. Accordingly, we tested the hypothesis that HBx enhanced hepatocarcinogenesis by increasing the expression of target genes of miR-18b. Moreover, we identified nucleolar spindle-associated protein 1(NUSAP1) as one of the target genes of miR-18b.NUSAP1 was expressed at high levels in liver cancer tissues. Interestingly, HBx up-regulated NUSAP1 by suppressing miR-18b.Functionally, miR-18b significantly inhibited the proliferation of hepatoma cells by depressing NUSAP1 levels in vivo and in vitro.Conclusions: Thus, we conclude that the targeting of NUSAP1 mRNA by the tumor suppressor miR-18b is controlled by HBxmodulated promoter methylation during the host-virus interaction, leading to hepatocarcinogenesis. Our findings provide new insights into the mechanism by which HBx-mediated miRNAs modulate hepatocarcinogenesis.

Clinical application of self-expanding metallic stent in the management of acute left-sided colorectal malignant obstruction

瞄准：在尖锐左边的颜色的管理用自我膨胀的金属性的斯滕特氏印模膏(SEMS ) 的申请总结我们的经验表面的恶意的阻塞。方法：经历在 2000 年 4 月和 2004 年 1 月之间的 SEMS 的放置的所有病人的回顾的图表评论被执行。结果：SEMS 的插入与偶尔的内视镜的帮助在 fluoroscopic 指导下面在 26 个病人被尝试。损害的地点位于二个病人，的结肠左曲七个病人，的左冒号八个病人的 S 字形的冒号和九个病人的直肠。SEMS 的打算的使用为在 7 个病人并且作为到在 19 个病人的选任的外科的一座桥的减轻。在后者组， SEMS 的放置允许外科手术前全身并且肠准备和下列一个阶段吻合。成功的斯滕特氏印模膏放置在 22 被完成(85%) 26 个病人。临床的肠阻塞在 21 在成功的斯滕特氏印模膏放置以后解决了 24 个小时(95%) 病人。三 SEMS 相关的次要的复杂并发症发生了，二 stents 移植了，一个人引起了肛门疼痛。结论：SEMS 在尖锐恶意的颜色的管理代表一个有效、安全的工具表面的阻塞。作为到外科的一座桥， SEMS 能为系统的支持和肠准备提供时间并且排除对烘便的转向或在桌子上洗室年龄的需要。作为一项辩解的措施， SEMS 能为突现的结肠开口术消除需要。