Fine-tuning of stable organic free-radical photosensitizers for photodynamic immunotherapy.

Photodynamic immunotherapy (PDI) is an innovative approach to cancer treatment that utilizes photodynamic therapy (PDT) and photosensitizers (PSs) to induce immunogenic cell death (ICD). However, currently most commonly used PSs have restricted capabilities to generate reactive oxygen species (ROS) via a type-II mechanism under hypoxic environments, which limits their effectiveness in PDI. To overcome this, we propose a novel approach for constructing oxygen independent PSs based on stable organic free-radical molecules. By fine-tuning the characteristics of tris(2,4,6-trichlorophenyl)-methyl (TTM) radicals through the incorporation of electron-donating moieties, we successfully found that TTMIndoOMe could produce substantial amounts of ROS even in hypoxic environments. In vitro experiments showed that TTMIndoOMe could effectively produce O2˙-, kill tumor cells and trigger ICD. Moreover, in vivo experiments also demonstrated that TTMIndoOMe could further trigger anti-tumor immune response and exhibit a superior therapeutic effect compared with PDT alone. Our study offers a promising approach towards the development of next-generation PSs functioning efficiently even under hypoxic conditions and also paves the way for the creation of more effective PSs for PDI.

In Situ Photoacoustic Visualization of Pneumonia Induced by MRSA and Specific Identifying Tumor-Homing Bacteria.

Optical imaging holds great promise for monitoring bacterial infectious processes and drug resistance with high temporal-spatial resolution. Currently, the diagnosis of deep-seated bacterial infections in vivo with fluorescence imaging, including near-infrared (NIR) fluorescence imaging technology, remains a significant challenge due to its limited tissue penetration depth. In this study, we developed a highly specific targeting probe, Cy7-Neo-NO2, by conjugating a bacterial 16S rRNA-targeted moiety, neomycin, with a bacterial nitroreductase (NTR)-activated NIR photoacoustic (PA) scaffold using our previously developed caged photoinduced electron transfer (a-PeT) approach. This conjugation effectively resolved probe aggregation issues in physiological conditions and substantially enhanced its reactivity toward bacterial NTR. Notably, Cy7-Neo-NO2 enabled the first in situ photoacoustic imaging of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA), as well as the detection of bacteria within tumors. Furthermore, upon NIR irradiation, Cy7-Neo-NO2 successfully inhibited MRSA growth through a synergistic effect combining photothermal therapy and photodynamic therapy. Our results provided an effective tool for obtaining exceptional PA agents for accurate diagnosis, therapeutic evaluation of deep-seated bacterial infections in vivo, and intratumoral bacteria-specific recognition.

Polymyxin-based fluorescent probes to combat Gram-negative antimicrobial resistance.

Reliable diagnostic approaches especially those targeting critical Gram-negative bacteria are urgently needed for the prevention of antimicrobial resistance. Polymyxin B (PMB) which specifically targets the outer membrane of Gram-negative bacteria is the last-line antibiotic against life-threatening multidrug-resistant Gram-negative bacteria. However, increasing number of studies have reported the spread of PMB-resistant strains. With the aim to specifically detect Gram-negative bacteria and potentially reduce the irrational use of antibiotics, we herein rationally designed two Gram-negative bacteria specific fluorescent probes based on our previous activity-toxicity optimization of PMB. The in vitro probe PMS-Dns showed fast and selective labeling of Gram-negative pathogens in complex biological cultures. Subsequently, we constructed the caged in vivo fluorescent probe PMS-Cy-NO2 by conjugating bacterial nitroreductase (NTR)-activatable positive charged hydrophobic near-infrared (NIR) fluorophore with polymyxin scaffold. Significantly, PMS-Cy-NO2 exhibited excellent Gram-negative bacterial detection capability with the differentiation between Gram-positive and Gram-negative in a mouse skin infection model.

Thermally activated delayed fluorescence emitters: a thionation approach toward next-generation photosensitizers.

Achieving highly efficient intersystem crossing (ISC) remains a key focus in the design of heavy atom-free photosensitizers (PSs) for various photophysical and photochemical applications. Herein, we report a general and robust molecular design strategy for obtaining photoactivatable heavy atom-free PSs by performing a simple sulfur substitution of carbonyl oxygen atoms of a thermally activated delayed fluorescence (TADF) emitter. This thionation led to a significant fluorescence loss, resulting in an increased ISC transformation. Upon white-light irradiation, the sulfur-substituted TADF compound (S-AIOH-Cz) exhibited a long-lived fluorescence turn-on response, a long-lasting triplet state lifetime and a superior reactive oxygen species (ROS) generation ability, which is desirable for time-resolved fluorescence imaging and photodynamic disinfection against antimicrobial resistance.

Encephalo-duro-arterio-synangiosis for intracranial arterial steno-occlusive disease: a retrospective case series study of 40 cases / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of encephalo-duro-arterio-synangiosis (EDAS) for intracranial atherosclerotic steno-occlusive disease (ICASD).Methods:Patients with symptomatic ICASD received EDAS treatment in the Department of Neurosurgery, the PLA General Hospital from January 2018 to January 2019 were retrospectively included. The baseline information, perioperative complications, primary endpoint events, and changes in modified Rankin Scale (mRS) scores before and after surgery were collected. The primary endpoint event was any stroke/death that occurred within 30 d after enrollment. The secondary endpoint events were any stroke/death, non-stroke bleeding (subdural or epidural bleeding), and clinical functional improvement after 30 d. The clinical functional improvement was defined as a decrease of ≥1 in the mRS score compared to before surgery.Results:A total of 40 patients were included, including 30 males and 10 females, aged 53.9±8.6 years old. The clinical symptoms were mainly limb weakness and dizziness. One case of ischemic stroke and one case of hemorrhagic stroke occurred during the perioperative period. The primary endpoint event incidence was 2.5%. The patients were followed up for 49.75±2.99 months after surgery. One patient died of cerebral hemorrhage 31 months after surgery, and one patient developed acute ischemic stroke 35 months after surgery. The postoperative mRS scores of 34 patients decreased compared to before surgery, and the clinical function improvement rate was 85%. The mRS score increased in 2 cases after surgery compared to before surgery and 4 cases had no change.Conclusion:EDAS can improve the clinical function of patients with symptomatic ICASD and reduce the incidence of long-term stroke.

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC / 医学前沿

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

Hyperglycemia in Diabetic Skin Infections Promotes Staphylococcus aureus Virulence Factor Aureolysin: Visualization by Molecular Imaging.

Bacterial skin infections are common in diabetic patients, with Staphylococcus aureus (S. aureus) being the most commonly isolated, causing comorbidities such as increased mortality and long-term hospitalization. While precise mechanisms remain to be determined, hyperglycemia represents an important pathogenetic factor responsible for the increased risk of S. aureus infection. Herein, we constructed a series of ratiometric fluorescent molecular probes for aureolysin (Aur), a major virulence factor in S. aureus. Using probe 1, we were able to determine specific Aur activity in both cells and tissues. We also observed that elevated glucose levels led to 2-fold higher Aur expression in S. aureus cultures. In a diabetic mouse model, we used molecular imaging to demonstrate that hyperglycemia tripled S. aureus Aur virulence compared to nondiabetic mice, resulting in more severe infections.

Safety and efficacy of immune checkpoint inhibitors therapy in liver transplantation recipients: an analysis report of literature published / 中华器官移植杂志

Objective:To explore the clinical applications and therapeutic outcomes of immune checkpoint inhibitors(ICIs)on liver transplantation(LT)recipients after tumor development.Methods:Eight databases including PubMed, China National Knowledge Infrastructure, Wanfang Data, CQVIP, PubMed, EMBASE, Web of Science and Google scholar were accessed for searching the relevant literature articles in both Chinese and English from the establishment of databases to December 31, 2021. Disease response, adverse reactions and prognoses of patients with malignant tumors after LT and receiving ICIs were analyzed.Results:The patient was diagnosed as chronic rejection plus drug-induced liver injury by liver biopsy. After intermittent treatment with DPMAS plus plasma exchange and immunosuppressants, he finally died of tumor recurrence at 37 months after LT. After screening, a total of 28 articles on the application of ICIs after LT were retrieved. In these articles, there were 47 patients(37 males and 10 females)with a median age of 57(14-71)years and the predominant type of tumor after LT was hepatocellular carcinoma(28/47, 59.6%), followed by malignant melanoma in 11 cases (23.4%), non-small cell lung cancer in 3 cases(6.4%), colorectal cancer, cholangiocarcinoma, squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and post transplant lymphoproliferative disease(PTLD) in 1 case(2.1%). The overall remission rate after ICI treatment was 29.8%(14/47)and the disease progression rate 68.1%(32/47). Among them, 31.9%(15/47)had immune rejection. Case fatality rate was 61.7%(29/47)and median survival time 6.5(0.3-48.0)months.Conclusions:Depending on existing publications, among those LT recipients with malignant tumors treated by ICIs, the rate of graft rejection and patient mortality are higher. ICIs should be carefully considered for LT patients and further researches are required.

Incidence and risk factors analysis of colorectal adenomatous polyps in recipients after liver transplantation / 器官移植

Objective To analyze the incidence and risk factors of colorectal adenomatous polyps (CAP) in recipients after liver transplantation. Methods Seventy-seven liver transplant recipients and 231 individuals undergoing colonoscopy during physical examination were recruited in this study. The incidence of CAP and pathological examination results were analyzed. Clinical data of liver transplant recipients were collected. According to the incidence of CAP, liver transplant recipients were divided into the CAP group (n=28) and non-CAP group (n=49). The risk factors of CAP after liver transplantation were identified. Results The 5-year cumulative incidence rates of colorectal polyps in liver transplant recipients and physical examination individuals were 43% and 34%, and 29% and 23% for the 5-year cumulative incidence rates of CAP, with no significant differences (both P > 0.05). Among all liver transplant recipients, 65 polyps were detected. The quantity of polyps in 1 case was excessively high and not counted. Multiple polyps were identified in certain recipients. Five polyps were not prepared for pathological examination due to small size. Pathological examination of 60 polyps demonstrated 25 inflammatory polyps, 33 CAP (8 complicated with low-grade intraepithelial neoplasia and 3 complicated with high-grade intraepithelial neoplasia), and 2 well-differentiated adenocarcinoma. Cox model analysis prompted that use of ciclosporine after liver transplantation was an independent risk factor for CAP in the recipients. Conclusions The risk of CAP is slightly elevated after liver transplantation. Postoperative use of ciclosporine is an independent risk factor for CAP in recipients after liver transplantation. Colonoscopy should be emphasized in the recipients after liver transplantation.

De novo malignancies after liver transplantation: clinical characteristics and management strategies / 中华肝胆外科杂志

Objective:To investigate the clinical characteristics of de novo malignancies (DNMs) after liver transplantation (LT) and to study the clinical management strategies.Methods:Adult LT recipients who were regularly followed-up in the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2005 to April 2021 were enrolled in this study. The clinical characteristics of DNMs were retrospectively analyzed. Of 601 LT recipients, there were 105 females and 496 males, aged (51.4±9.6) years old. They were divided into the DNMs group ( n=26) and the non-DNMs group ( n=575) according to whether there were DNMs on followed-up. Clinical data including age, sex, basic diseases before LT and operation time were collected. These patients were follow-up in outpatient clinics. Results:Twenty-six patients were diagnosed to develop DNMs after LT, but there were 28 DNMs (of which 2 patients were diagnosed to have DNMs twice). The incidence of DNMs after LT was 4.3% (26/601), the median time from LT to DNMs was 42 (20, 70) months, and the cumulative incidence rates of DNMs were 0.5%, 2.0%, 6.3%, 21.0% and 34.5% at 1, 3, 5, 10 and 15 years after LT, respectively. Among the 28 DNMs, digestive system tumors were most common, with 17 lesions (60.7%), followed by 3 lesions (11.1%) of lung cancer, 2 lesions (7.4%) of lymphoproliferative diseases, and 1 lesion (3.7%) of cervical cancer, thyroid cancer, soft palate cancer, eyelid cancer, laryngeal cancer, and prostate cancer. The follow-up time of 55.9 (36.6, 102.5) months in the DNMs group after LT was longer than the 33.4 (18.5, 58.9) months in the non-DNMs group ( P<0.001). The 1, 5, and 10 year survival rates of patients with DNMs after LT were 96.3%, 83.5%, and 49.8%, respectively. The 1, 5, and 10 year survival rates of patients with non-DNMs after LT were 94.5%, 77.7%, and 75.4%, respectively. There was no significant difference in the cumulative survival rates between the two groups (log rank=0.402, P=0.526). Conclusion:The incidence of DNMs in LT recipients was 4.3%. The majority of them were digestive system tumors. Early diagnosis and treatment of DNMs significantly improved the prognosis and quality of life of these patients.

Helicobacter pylori infection in liver transplant recipients / 中华肝胆外科杂志

Objective:To determine the prevalence of Helicobacter pylori (Hp) infection in orthotopic liver transplantation (LT) recipients, and to study the efficacy and safety of Hp eradication therapy.Methods:13C-urea breath test was carried out between July 2018 and October 2019. There were 104 males and 26 females with an average age of 52.1 year for these LT recipients who were regularly followed-up in the Organ Transplant Center, the Affiliated Hospital of Qingdao University. Propensity scoring was used to match age and gender in a ratio of 1∶3. A healthy group of individuals consisting of 299 males and 91 females, with an average age of 51.8 years, were selected as the control group also in a ratio of 1∶3. All patients underwent 13C-urea breath test to evaluate Hp infection and results of quadruple therapy. Results:The prevalence of Hp infection among the LT recipients was 18.5%(24/130) which was significantly lower than the control group 36.4% (142/390) (χ 2=14.400, P<0.001). Among the recipients who received LT and 13C-urea breath test for less than 1 year, 1-3 years and more than 3 years, the prevalences of Hp infection were 14.3% (6/42), 17.8%(8/45) and 23.3%(10/43), respectively. Although the prevalence of Hp showed a gradually increasing trend, no correlation between Hp infection and duration from LT was observed (χ 2=1.321, P=0.517). Seventeen Hp positive recipients underwent Hp eradication therapy. The success rate of Hp eradication was 100.0%(17/17). Immunosuppressant concentration was monitored regularly in 10 patients. During Hp eradication, the blood concentration of immunosuppressant increased from 1.7 to 3.6 times, and the drug dosage was reduced to one half to one third of what it was before Hp eradication. Seven of these 17 recipients suffered from adverse effects caused by increased levels of blood concentration of immunosuppressants, including headache, hypertension, insomnia and irritability. Normal liver and kidney functions were observed during eradication. Conclusion:In this study, the prevalence of Hp infection among liver transplant recipients was 18.5%. The success rate of Hp eradication was 100% using bismuth-containing quadruple therapy. The dosage of immunosuppressant required to be monitored, and if necessary, adjusted during eradication to reduce adverse side effects.

Simple and robust differentiation of Ganoderma species by high performance thin-layer chromatography coupled with single quadrupole mass spectrometry QDa / 中国天然药物

In this study, a high performance thin-layer chromatography/single quadrupole mass spectrometry QDa (HPTLC-QDa) method for robust authentication of Ganoderma lucidum, a popular and valuable herbal medicine, has been developed. This method is simple and practical, which allows direct generation of characteristic mass spectra from the HPTLC plates automatically with the application of in situ solvent desorption interface. The HPTLC silica gel plates were developed with toluene-ethyl formate-formic acid (5 : 5 : 0.2, V/V) and all bands were transferred to QDa system directly in situ using 80% methanol with 0.1% formic acid as desorption solvent. The acquired HPTLC-QDa spectra showed that luminous yellow band b3, containing ganoderic acid B/G/H and ganodeneric acid B, the major active components of Ganoderma, could be found only in G. lucidum and G. lucidum (Antler-shaped), but not in G. sinense and G. applanatum. Moreover, bands b13 and b14 with m/z 475/477 and m/z 475/491/495, respectively, could be detected in G. lucidum (Antler-shaped), but not in G. lucidum, thus allowing simple and robust authentication of G. lucidum with confused species. This method is proved to be simple, practical and reproducible, which can be extended to analyze other herbal medicines.

A single component self-assembled thermally activated delayed fluorescence nanoprobe.

A novel versatile thermally activated delayed fluorescence (TADF) nanoprobe, AI-Cz-NP, was designed and fabricated through self-assembly of a single-component amphiphilic monomer for potential applications in confocal imaging and time-resolved fluorescence imaging.

Diagnosis and treatment of de novo gastric cancer after liver transplantation: 3 cases reports and literature review / 中华器官移植杂志

Objective:To summarize the experience of diagnosing and treating de novo gastric cancer after liver transplantation(LT).Methods:The clinical data were analyzed for 3 LT patients with de novo gastric cancer during follow-ups.Results:The mean diagnostic age was 57(47~67)years, mean time interval between LT and diagnosis of de novo gastric cancer 82(40~122)months and mean follow-up time 23(4~42)months. After surgical resections, 2 survived and another died of recurrence.Conclusions:LT recipients are recommended for regular screening of de novo malignancies. Regular endoscopic screening of gastric tumors contributes to early detection, diagnosis and treatment. It may improve long-term survival outcomes in LT recipients.

Literature analysis report of de novo malignant tumors of digestive system after liver transplantation in China / 器官移植

Objective To investigate the incidence of de novo malignant tumors of the digestive system after liver transplantation (LT) in China. Methods Relevant literature review was performed from Wanfang data, China National Knowledge Infrastructure (CNKI) and Chongqing VIP. The retrieval time started from the establishment of each database to May 9, 2019. The Chinese search terms were liver transplantation+ postoperative/de novo+ malignant tumor/cancer. The age distribution, sex composition, time of diagnosis, involved organs, treatment and clinical prognosis of recipients with de novo malignant tumors of the digestive system after LT in China were retrospectively analyzed. Results After literature screening, 16 articles were eventually selected including 47 cases of de novo malignant tumors of the digestive system after LT. A majority of them were male recipients. The age of the recipients was 51 (23-65) years old, most of them were middle age (45-59 years old). The average time of diagnosis of de novo malignant tumors of the digestive system after operation was 43 (2-156) months, with the highest number of cases within postoperative 1-3 years. Colon and stomach were the most common tumor sites. Surgery combined with radiotherapy and chemotherapy remained the main treatment option. However, the overall clinical prognosis of patients with de novo malignant tumors of the digestive system after LT was poor with a mortality rate of 51%. Conclusions In China, colon cancer and gastric cancer are the main de novo malignant tumors of the digestive system after LT. The overall clinical prognosis of patients with de novo malignant tumors of the digestive system is poor. Sufficient attention should be paid to postoperative monitoring and prevention.

Retrospective analysis of cuffed-tunneled catheters in pediatric patients receiving maintenance hemodialysis / 中华儿科杂志

Objective@#To summarize the characteristics of cuffed-tunneled catheters insertion and investigate the values of cuffed-tunneled catheters in pediatric patients.@*Methods@#Between March 2015 and July 2017, all the pediatric patients who received maintenance hemodialysis at least 3 consecutive months in our center were included. Sixteen cuffed-tunneled hemodialysis catheters were inserted in patients for long-term hemodialysis access. The clinical manifestations and complications were retrospectively reviewed.@*Results@#Fifteen pediatric patients with end stage ranal disease (ESRD) were included in this study and they received 16 cuffed-tunneled catheters for long-term vascular access, including 10 males and 5 females; median age at start of catheter insertion was 11.5 (4.2-14.5) years. Body weight was (27.8±8.0)kg (16.0-39.4 kg) . The size and the length of the catheters were based on the height of patients as follows: 28 cm for (115.6±10.6) cm (102.0-130.0 cm) ,36 cm for (148.6±9.9)cm (140.0-167.0 cm) . Cuffed-tunneled catheters outcome: 10 cuffed-tunneled catheters were still functional at the end of the study; 5 catheters were removed after successful kidney transplantation. Catheter failure occurred in 1 out of 16 cuffed-tunneled catheters due to catheter-related infections. The median catheter survival time was 11.9 months (range 3.5-21.3 months). Complications of cuffed-tunneled catheters: Catheter placements operation was successful in 15 cases using ultrasound guidance. No serious complications were observed in any patients receiving catheter inserting operation. The overall rate of catheter-related infections and thrombosis/malposition was 6.3% and 18.7%, respectively.@*Conclusions@#Ultrasound guidance is suggested in pediatric patients during the catheters insertion. The size and the length of the catheters should be based on the height of patients. Cuffed-tunneled hemodialysis catheters could be effectively used for maintenance of hemodialysis vascular access for pediatric patients with ESRD.

The risk factors and the etiology analysis of early infection in recipients following liver transplantation / 中华器官移植杂志

Objective To explore the risk factors,the distribution of etiology and drug resistance status of patients with early infection (3 months) after liver transplantation,and to provide reference for clinical diagnosis and treatment.Methods The clinical data of 112 recipients from February 2014 to December 2015 were collected,and logistic regression analysis was performed on the risk factors of early postoperative infection in liver transplant patients.The independent risk factors of infection after liver transplantation were screened out.At the same time,the results of pathogen culture and drug sensitivity test were statistically described.Results The independent risk factors for infection at 3th month after liver transplantation included the operative time ≥600 min [P =0.003,odds ratio (OR) =9.996,95 ％ confidence interval (95 ％ CI),2.221-44.981],intensive care unit (ICU) ≥6 days (P =0.010,OR =6.306,95％ CI =1.563-25.437),Child-Pugh grade of C (P =0.023,OR =6.298,95％ CI =1.294-30.659).Of the 112 liver transplant recipients,59 had an infection (52.68％),and 168 stains of pathogens were isolated.The positive rate of the specimens was highest in sputum,followed by bile,ascites,drainage and catheter end,blood,deep vein catheter,middle urinary,pleural effusion and peripherally inserted central catheter (PICC).The detectable rate of gram-negative bacteria,gram-positive bacteria,fungi and viruses was 46.43％ (78 strains),29.76％ (50 strains),18.45％ (31 strains),and 5.36％ (9 strains) respectively.Infection occurred mainly within 1 month after surgery,accounting for about 80.36％ (135 strains),especially at 1st week after surgery,accounting for about 34.52％ (58 strains).Gram-positive bacteria had a higher drug resistance rate,including penicillins,macrolides,aminoglycosides,quinolones,linamides,etc.especially in the highest rate of Enterococcus faeciurr.Gram-negative bacteria were individualized based on the different strains of the bacteria,and they were relatively low in the resistance of the carbapene.Conclusion Infection is one of the most common complications after liver transplantation.To reduce the incidence of infection after liver transplantation,efforts should be made to shorten the duration of operation and ICU stay time,improve the basic nutritional status of recipients,and enhance monitoring of the recipient's infection after liver transplantation,to further increase the survival rate of postoperative liver transplantation recipients and improve the quality of life.

Prognosis analysis of hepatitis B virus recurrence after liver transplantation: a single-center study of 38 cases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the prognosis of hepatitis B virus (HBV) recurrence after liver transplantation.</p><p><b>METHODS</b>Thirty-eight patients (37 males; 1 female) with HBV-related end-stage liver disease underwent liver transplantation at our institute between December 1998 and November 2009 and experienced HBV recurrence. Clinical data from pre-transplant and follow-up examinations were retrospectively retrieved from medical records, and included serologic indices of HBV (HBV DNA, markers of liver function) and histological findings from liver biopsy.</p><p><b>RESULTS</b>The median follow-up time was 45.1 months. The median time to HBV recurrence after transplantation was 31.8 months (range: 0.3 to 72.8 months) for histologically benign cases and 13.7 months (range: 0.3 to 66.6 months) for malignant cases. HBV DNA gene mutations were detected in 21% (8/38) of cases. Eighteen patients were treated with entecavir or adefovir, with respect to gene mutations, and HBV DNA fell below 103 copies/ml and liver function became normal. Twenty-two patients died, and causes of death included hepatocellular carcinoma (HCC, n=18), organ failure (n=2), or infection (n=1).</p><p><b>CONCLUSION</b>HBV gene mutations and HCC recurrence were important risk factors for HBV recurrence in our study population. In addition, patients with benign liver diseases who received salvage therapy with adefovir or entecavir achieved a satisfactory prognosis.</p>

Diagnosis and treatment of hepatic venous outflow obstruction after pediatric liver transplantation / 中华肝胆外科杂志

ObjectiveTo investigate the diagnosis and treatment of hepatic venous outflow obstruction(HVOO) after pediatric liver transplantation.MethodsFrom Jan.2000 to Dec.2009,48 children received liver transplantation in the Department of Liver Transplantation,First Central Hospital,Tianjin.There were 3 patients who developed HVOO (2 received liver transplantation in our center,while the third from another centre).The HVOO was diagnosed by color Doppler ultrasound (CDUS),computed tomography (CT),and angiography of inferior vena cava (IVC).The patients received balloon dilation and/or stent placement and followed-up with regular monitoring.ResultsIn our center,the incidence rate of HVOO was 4.17％ (2/48).The time of onset was 2 months to 1 year postoperatively.The pressure gradient between the hepatic vein and the right atrium was from 6 to 30mmHg.After treatment,the venous pressure gradient decreased from 4 to 10mmHg.Resolution of clinical symptoms was achieved in these patients.HVOO relapsed in two patients who received balloon angioplasty only.The clinical symptoms were relieved after repeated balloon dilation in one and stent placement in the other.There were no further complications after these procedures.All patients were alive at a follow-up from 2 months to 9 years.ConclusionThe incidence of HVOO after pediatric liver transplantation was not high,but HVOO led to serious consequences.Balloon dilation and/or stent implantation were safe and efficacious treatments for HVOO after pediatric liver transplantation.

Combination of low-dose HBIg and Nucleoside analogues to prevent recurrent hepatitis B virus after liver transplantation: a retrospective analysis of 1506 cases / 中华肝胆外科杂志

Objective To evaluate the preventive effect of combination of low-dose HBIg and Nucleoside analogues on recurrence of hepatitis B after liver transplantation. Methods Retrospectively analyzed HBV status and recurrence in patients accepting Nucleoside analogues plus low-dose HBIg as prophylaxis treatment after liver transplantation for HBV-related end-stage liver disease from December 1998 to Octomber 2009 in our center. Results In all the 1506 patients whose survival time >30 d after liver transplantation, 37 patients showed HBV recurrence, the HBV cumulative-recurrence rate of 1, 2, 3, 4, 5 and 6y was 1.3%,2. 4%,2. 7%,2. 9%,3. 7% and 4.6% respectively. The time of recurrence varied from 0. 3 to 66. 6 months (median 12. 8 months) after transplantation. Virus mutation could be tested in 9 cases of the 37 recurrence patients, including 4 YMDD cases, 2 YMDD + YIDD cases, 1 YMDD+YVDD cases, 1 YVDD case,and 1 YIDD case. Conclusions Liver transplantation is the principal therapeutic method for the patient with end-stage liver diseases related to HBV, with the effectively prophylaxis treatment to aim directly at HBV recurrence. If the patients who got HBV recurrence received targeted treatments, the situation can be controlled satisfactorily.