Bilateral lung transplantation,a new option for pulmonary metastasis from hepatocellular carcinoma?

To the Editor:The lung is the most frequent site of extrahepatic hepatocellular carcinoma(HCC)recurrence after liver transplantation(LT).Pulmonary metastasis from hepatocellular carcinoma(PM-HCC)carries a poor prognosis as the patient could finally die of pulmonary failure secondary to the tumor despite maintaining ideal liver function.

Use of veno-arterial extracorporeal membrane oxygenation in the fi rst successful combined lung-liver transplantation patient in China

Dear editor,Extracorporeal membrane oxygenation(ECMO)is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy.[1]ECMO use has been exponentially increasing over the last decade and is now considered a mainstream lifesaving treatment modality in critical care medicine.Many studies report ECMO use in patients with acute respiratory distress syndrome refractory to conventional clinical support,in-hospital cardiac arrest,and cardiogenic refractory shock.[1-3]Herein,we report the use of veno-arterial ECMO(VA-ECMO)in the first successful combined lung-liver transplantation(CLLT)patient in China.

Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.

CP-25 inhibits the functions of activated human B cells through regulating BAFF-TRAF2-NF-κB and TNF-alpha-TRAF2-NF-κB signaling

OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) of normal human were isolated using magnetic cell separation(MACS) by a positive selection.B cells(107 cells·mL^(-1)) were stimulated by BAFF(100 ng·mL^(-1))or TNF-alpha(100 ng·mL^(-1)) for two hours,and then were treated with CP-25(10-5 mol·L^(-1)) or Rituximab(5 μg·mL^(-1)) or Etanercept(10 μg·mL^(-1)).B cell proliferation was detected by CCK-8.B cell subsets and BAFF receptors(BAFFR,BCMA and TACI) were analyzed by flow cytometry.The expression of TNFR1 and TNFR2 on B cells was analyzed by flow cytometry.The expression of MKK3,MKK6,P-p38,P-p65,TRAF2 and p100/52 was analyzed by Western blotting.RESULTS CP-25 inhibited B cells proliferation stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept reduced the percentage and numbers of CD19^+B cells,CD19^+CD20^+B cells,CD19^+CD27^+B cells and CD19^+CD20^+CD27^+B cells induced by BAFF or TNF-alpha.CP-25 down-regulated the high expression of BAFFR,BCMA and TACI stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated the expression of MKK3,P-p38,P-p65,TRAF2 and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha.CONCLUSION CP-25 regulated moderately activated B cells function by by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway.This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

Single-lung transplantation for pulmonary alveolar microlithiasis: A case report

BACKGROUND Pulmonary alveolar microlithiasis(PAM)is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths.Currently,effective therapeutics for PAM are not available,and the only treatment for end-stage lung disease is lung transplantation(LuTx).Further,there are few reports that focus on LuTx for the treatment of PAM,and the follow-up reports of postoperative imaging are even rarer.CASE SUMMARY A 52-year-old man presented to Shanghai Pulmonary Hospital in 2017 after experiencing shortness of breath and exacerbation.The patient was diagnosed with PAM and referred for single-LuTx(SLuTx)on March 14,2018.Preoperative imaging results from a chest X-ray demonstrated bilateral,diffuse,symmetrical,sandstorm-like radiopaque micronodules,and pneumothorax and a computed tomography scan revealed minute,calcified military nodules in both lungs.We performed a left SLuTx,and intraoperative pathology was consistent with PAM.One week after surgery,a chest X-ray revealed slight exudation of the left lung,and one month later,the left transplanted lung exhibited good dilation,mild pulmonary perfusion injury with local infection,and left pleural effusion.Fiberoptic bronchoscopy revealed left hyperplastic granulation at the left bronchial anastomosis.Multiple sputum cultures suggested the presence of Klebsiella pneumoniae and Acinetobacter baumannii.The last follow-up was conducted in April 2019;the patient recovered well.CONCLUSION This case presents the imaging findings of a patient with PAM before and after LuTx and confirms the effectiveness of LuTx for the treatment of this disease.

A novel anti-inflammatory and immunomodulatory drug CP-25 alleviated collagen induced arthritis by down-regulating BAFF-NF-κκB signaling pathway

OBJECTIVE To investigated the regulatory effect of paeoniflorin-6′-O-benzene sulfonate(CP-25) on B cell activating factor(BAFF)/BAFF receptor-nuclear factor of kappa B(NF-κB) signaling in B cell of collagen induced-arthritis(CIA) mice.METHODS Mice CIA was induced by injection of typeⅡcollagen(CⅡ).The arthritis index(AI) and swollen joint count(SJC) were assessed,and histopathology of spleen and joints were observed.The percentage of B cells subsets,BAFF receptor expressions were analyzed by flow cytometry.BAFF and immunoglobulin(Ig) levels were measured by protein antibody array.The expressions of TRAF2,MKK3,MKK6,p-P38,and p-NF-κB65 in NF-κB signaling mediated by BAFF were analyzed by western blot.RESULTS CP-25 decreased AI and SJC,restored abnormal weights,reduced thymus index and spleen index,inhibited T/B cells proliferation,alleviated the histopathology of spleen and joints in CIA mice.CP-25 also reduced high levels of serum BAFF and immunoglobulin,decreased CD19+B cells,CD19+CD27+B cells,and CD19-CD27+CD138+plasma cells,inhibited BAFFR and TACI expressions,decreased the expressions of TRAF2,MKK3,MKK6,p-P38,and p-NF-κB65.Compared with biological agents etanercept and rituximab,CP-25 restored high T cells proliferation and percentages of B subsets to normal level,and recovered the high levels of IgA,IgD,IgG1,IgG2 a and high expressions molecules in NF-κB signaling to normal levels.The action intensity of rituximab and etanercept was more strong than CP-25.The inhibitor effects of rituximab and etanercept on AI and SJC,thymus index,proliferation of T cells and B cells subsets were strong,and down-regulated the indexes to under normal levels.CONCLUSION CP-25 might be a promising anti-inflammatory immune and regulation drug,which alleviated CIA and regulated the functions of B cells through BAFF/BAFF receptor-NF-κB signaling.

Ginsenoside metabolite compound K alleviate collegen-induced arthritis through impairing dendritic cells function

OBJECTIVE Ginsenoside metabolite compound K(CK)is a degradation product of ginsenoside in the intestine by bacteria.The anti-inflammatory and immunomodulatory activities of CK have been reported.This study investigated whether CK exerted its immunoregulatory effect through modulation of dendritic cells(DCs)function.METHODS In vivo,severity of collegen-induced arthritis(CIA),T cells and DCs subsets,phenotype of DC were assayed by flow cytometry,CCL19 and CCL21 level in lymph nodes assayed by ELISA.In vitro,bone marrow-derived DCs from normal mice were matured with lipopolysaccharide and treated with CK for 48 h.In vivo,bone marrow-derived DCs were generated from CIA mice before and 2 weeks into CK treatment.DCs were analyzed for migration,phenotype and T-cell stimulatory capacity.RESULTS CK alleviated the severity of CIA,decreased pD Cs and mo-DCs,increased na?ve T cells in CIA mice lymph nodes,and suppressed CCL21 expression in lymph nodes.CK suppressed DCs migration induced by CCL21 and T cells-stimulatory capability of DC,down-regulated LPS-induced expression of CD80,CD86,MHCII and CCR7 on DCs.CONCLUSION This study elucidated the novel immunomodulatory property of CK via impairing function of DCs in priming T cells activation.These results provide an interesting novel insight into the potential mechanism by which CK contribute to the restoration of immunoregulation in autoimmune conditions.

Chinese expert consensus on organ protection of transplantation(2022 edition)

Introduction Organ transplantation increases survival and improves qual-ity of life to many patients with end-stage organ failure.Or-gan shortage is a worldwide problem that restricts organ trans-plantation[1].Organ procurement and preservation as well as ischemia-reperfusion injury(IRI)after transplantation are the im-portant factors affecting prognosis of recipients.Since the de-velopment of organ transplantation technology in the 20th cen-tury,organ protection technology has been a most promising con-cept in this field.Organ preservation solutions such as the Collins solution,University of Wisconsin(UW)solution,and histidine-tryptophan-ketoglutarate(HTK)solution were developed sequen-tially[2],which developed rapidly in static cold storage(SCS)tech-niques.SCS remains the standard preservation technique for organ transplantation[2].

Relationship between quality of life and adolescent glycolipid metabolism disorder:A cohort study

BACKGROUND The prevalence of glucolipid metabolic disorders(GLMDs)in children and adolescents has a recognized association with cardiovascular diseases and type 2 diabetes mellitus in adulthood.Therefore,it is important to enhance our understanding of the risk factors for GLMD in childhood and adolescence.AIM To explore the relationship between quality of life(QoL)and adolescent GLMD.METHODS This study included 1956 samples in 2019 from a cohort study established in 2014.The QoL scale and glycolipid indexes were collected during follow-up;other covariates of perinatal factors,physical measures,and socioeconomic indicators were collected and adjusted.A generalized linear regression model and logistic regression model were used to analyse the correlation between QoL and GLMD.RESULTS Higher scores of QoL activity opportunity,learning ability and attitude,attitude towards doing homework,and living convenience domains correlated negatively with insulin and homeostasis model assessment insulin resistance(IR)levels.Psychosocial factors,QoL satisfaction factors,and total QoL scores had significant protective effects on insulin and IR levels.Activity opportunity,learning ability and attitude,attitude towards doing homework domains of QoL,psychosocial factor,and total score of QoL correlated positively with high density lipoprotein.In addition,the attitude towards doing homework domain was a protective factor for dyslipidaemia,IR>3,and increased fasting blood glucose;four factors,QoL and total QoL score correlated significantly negatively with IR>3.In subgroup analyses of sex,more domains of QoL correlated with insulin and triglyceride levels,dyslipidaemia,and IR>3 in females.Poor QoL was associated with an increased prevalence of GLMD,and the effect was more pronounced in males than in females.Measures to improve the QoL of adolescents are essential to reduce rates of GLMD.CONCLUSION Our study revealed that QoL scores mainly correlate negatively with the prevalence of GLMD in adolescents of the healthy population.The independent relationship between QoL and GLMD can be illustrated by adjusting for multiple covariates that may be associated with glycaemic index.In addition,among females,more QoL domains are associated with glycaemic index.

Lung transplantation in China between 2015 and 2018

Background:Lung transplantation(LT)has been demonstrated as the only effective therapy for patients with end-stage lung diseases.Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require wellorganized programs and registry data collection based on the large population.This study aimed to summarize and analyze the data of LT development in China.Methods:We retrospectively collected and analyzed data from the China Lung Transplantation Registry(CLuTR).Key data were reported from the registry with transplant types,indications,donor and recipient characteristics,outcomes and survival.The survival<30 days,1-year and 3-year survival rates were estimated with risk factors identified.Results:CLuTR contained data from 1053 lung transplants performed through January 1st,2015 to December 31st,2018 reported by 18 registered transplant centers.The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis.The total<30 days,1-year and 3-year survival rates in CLuTR were 81.45%,70.11%,and 61.16%with discrepancy by indications.Large proportion of recipients who were more than 60 years old required higher standard of care.Infection-related complications resulted in more death events in the early post-surgery periods.New York Heart Association grading at listing,extra-corporeal membrane oxygenation usage peri-transplantation,allograft dysfunction(primary graft dysfunction>Grade 0),renal insufficiency(estimated glomerular filtration rate<60 mL min_11.73 m^2),were independently associated with a higher risk for 3-year mortality in the entire cohort.Conclusions:Facing more end-stage of lung diseases and comorbidities,this study analyzed the outcomes and survival of LT recipients in China.Further prospectively stratified analyses with longer follow-up will be needed.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis

Background:Critical patients with the coronavirus disease 2019(COVID-19),even those whose nucleic acid test results had turned negative and those receiving maximal medical support,have been noted to progress to irreversible fatal respiratory failure.Lung transplantation(LT)as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.Methods:From February 10 to March 10,2020,three male patients were urgently assessed and listed for transplantation.After conducting a full ethical review and after obtaining assent from the family of the patients,we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.Results:Two of the three recipients survived post-LT and started participating in a rehabilitation program.Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved.The pathological results of the explanted lungs were concordant with the critical clinical manifestation,and provided insight towards better understanding of the disease.Government health affair systems,virology detection tools,and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.Conclusions:LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis.If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT,LT provided the final option for these patients to avoid certain death,with proper protection of transplant surgeons and medical staffs.By ensuring instant seamless care for both patients and medical teams,the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Advances in China＇s Organ Transplantation Achieved with the Guidance of Law

＂Transplantation＂ （Volume 97, Number 8, April 27, 2014） published an open letter from Professor Delmonico along with other seven professors to Mr. Xi Jinping, President of the People＇s Republic of China： China＇s Fight Against Corruption in Organ Transplantation. The article sharply posed this concern, thus evoking great attention at home and abroad within the transplant community. To this end, we hereby state our views and declare our position with regard to the concerns mentioned in the open letter about China＇s organ transplant undertaking.

The New Era of Organ Transplantation in China

On June 13, 2016, the US congress passed the bill H. Res. 343 based on the false statements regarding organ transplantation in China, which indicated serious miscommunication and misjudgment between China and the US on the issue. The bill is preceded and followed by a series distorted media reports by the Cable News Network and the New York Times.II,21 It is a typical act ofdemonizing China with colored glasses that boldly ignored the facts and fabricated the evidence for political purposes.

Bilateral lobar lung transplantation and a single lung transplantation using lungs from a single organ donor during coronavirus disease 2019 pandemic

To the Editor:During the coronavirus disease 2019(COVID-19)pandemic in China,cadaveric organ donation became drastically reduced,which exacerbated the waitlist morbidity and mortality of lung transplant(LTx)patients.We report a case where we were able to maximize the utilization of the lungs from a single cadaveric donor by performing a single left LTx for one recipient using the donor’s left lung,and by bipartitioning the donor’s right lung,we were able to perform bilateral lobar transplantation for another recipient.

Pediatric case report:successful bilateral lung transplantation performed to treat an 8-year-old girl with pulmonary interstitial fibrosis due to surfactant protein(SP)-C gene mutation

To the Editor:Pediatric lung transplantation is a highly specialized therapy for end stage pulmonary disease in children,and is performed in only a handful of transplant centers around the world.In the past decade,about 100 cases of pediatric lung transplantation have been performed annually all over the world.Most centers perform 1 to 4 pediatric lung transplantations annually,with only five centers performing more than five per year.Since 2007,our team has performed lung transplantations in 12 pediatric patients,among whom 11 were over 10 years old.

Pulmonary arterial stent for pulmonary trunk stenosis after size-mismatched lung transplantation

To the Editor: Appropriate donor-to-recipient size matching is of crucial importance in lung transplantation. Although tailoring of the lung has been described as a successful means of overcoming size disparities, its merits and demerits remain unclear. Here, we present a case of recurrent hypoxemia after unmatched single lung transplantation.

Green channel of human organ transport improved the utilization rate of Chinese citizens’donated lungs:a single-center data analysis

To the Editor:Organ donation after the citizen’s death program was fully launched in China in 2015.According to the allocation regulations of donated organs,all donated lungs must be allocated through the China Organ Transplant Response System(COTRS,www.cot.org.cn).[1]To fully optimize the implementation of organ transportation sharing policy and coordinate multiple government departments and social groups involved in the process,the"Green Channel of Human Organ Transport(GCHOT)"was established on May 6th,2016 in China[Supplementary Figure 1,http://links.lww.com/CM9/A431].[2]In this study,we reviewed and compared the status of lung transportation between the pre-and post-GCHOT periods based on data collected from the largest lung transplantation(LT)center in Wuxi,Jiangsu,China,with the aim of introducing the detailed process and implementation of GCHOT in China.

Respiratory arrest associated with polymyxin B in a lung transplant patient

To the Editor:The polymyxin antibiotics colistin(polymyxin E)and polymyxin B(PMB)became available in the 1950s;thus,they did not undergo contemporary drug development procedures.Their clinical use has recently resurged,assuming an important role as salvage therapv for otherwise untreatable gram-negative infection.[1]Multidrug-resistant(MDR)bacterial infections are primarily caused by gram-negative bacilli(GNB),such as Pseudomonas aeruginosa and Klebsiella pneumoniae^in lung transplant(LT)patients.[2]The increasing prevalence of MDR-GNB infections in LT patients has led to an upsurge in the use of these“older”drugs.During the treatment course,we should pay attention to severe and life-threatening respiratory paralysis caused by neuromuscular blockage associated with PMB.Herein,we report a rare case of a 67-year-old LT patient who suffered from respiratory arrest induced by PMB.