Objectives:Recent studies have shown that patients with chronic hepatitis B (CHB) have an increased prevalence of osteoporosis. However, the direct relationship between hepatitis B virus (HBV) DNA (representing the viral replication level) and bone mineral density (BMD) remains undefined. We aimed to investigate the association between HBV DNA levels and BMD in middle-aged and elderly CHB patients without prior antiviral therapy. Methods:This cross-sectional study recruited 362 untreated patients with CHB (men aged ≥50 years and postmenopausal women) who underwent both HBV DNA testing and dual-energy X-ray absorptiometry (DXA) within a 6-week interval. Based on bone mineral status, patients were categorized into three groups: normal BMD, osteopenia, and osteoporosis. Multiple regression and generalized additive models (GAMs) were applied to analyze associations between HBV DNA and BMD, whereas Receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminatory ability of HBV DNA levels to distinguish patients with osteoporosis. Exploratory mediation analysis of β-CTX and CRP was performed to assess indirect statistical associations linking HBV DNA with BMD. Results:Patients with osteoporosis had considerably higher HBV DNA levels than those with osteopenia or normal BMD. In multivariable analyses, each 1 log10 IU/mL increase in HBV DNA was associated with a 0.22-unit decrease in BMD T-score in the total cohort, with a stronger inverse association observed in males (β = -0.32) than in postmenopausal females (β = -0.16). GAMs revealed a continuous negative association between HBV DNA levels and BMD across the spectrum from normal bone density to osteoporosis (P for trend <0.001). HBV DNA demonstrated good between-group discriminatory ability for differentiating osteoporosis, with superior accuracy in males (area under the ROC curve = 0.847; optimal cut-off: 2.857 log10 IU/mL). Exploratory mediation analyses suggested that β-CTX and CRP may contribute to the association between HBV DNA and BMD in the total cohort; however, only β-CTX demonstrated a notable mediating effect in males. Notably, the direct association between HBV DNA levels and BMD remained evident across all mediating models. Conclusion:Higher HBV DNA levels are independently associated with lower BMD and demonstrate discriminatory ability for osteoporosis status in patients with CHB. Longitudinal studies are warranted to determine the predictive value of HBV DNA in predicting osteoporosis risk.

Portal vein thrombosis (PVT) is an important complication of liver cirrhosis, especially in patients with chronic hepatitis B (CHB). Previous studies have revealed that hepatitis B virus (HBV) infection and several serological indicators are associated with PVT; however, no predictive model including virological indicators of PVT in cirrhosis patients with CHB has been established. A retrospective cohort study including 252 CHB patients at the Affiliated Hospital of Qingdao University between January 1, 2012, and December 31, 2023, was performed. Baseline data were collected. PVT outcomes and antiviral virological responses were subsequently evaluated. We recognized risk factors and their hazard ratios. Propensity score matching (PSM) analysis was used to control for confounding factors. A clinical predictive model of PVT in CHB patients was established and verified. During a median follow-up time of 2568 days, 28 patients (11.11%) developed PVT. There were significant differences in age, portal vein diameter, spleen major axis, antiviral therapy time, prothrombin time (PT), blood platelet count, aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), alpha-feto protein (AFP), D-dimer, international normalized ratio (INR), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), serum hepatitis B virus deoxyribonucleic acid (HBV DNA) loads and levels after antiviral therapy, complications associated with hepatocellular cell cancer cirrhosis level, and antiviral responses between PVT patients and non-PVT patients. The effect of antiviral therapy was worse in more severe cirrhosis. There were greater PVT risks in patients with VBT antiviral responses, larger major axes in the spleen, and higher hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) levels. After controlling for confounding factors with PSM analysis, there was still a higher PVT risk in patients with adverse virological responses. A predictive nomogram for PVT in CHB patients was established and validated. PVT is a common complication in cirrhosis patients with CHB. Favorable virological responses are beneficial for lowering the risk of PVT in CHB patients. HCC, virological response, age, portal vein diameter, splenic major axis, PT, PLT, HBsAg, and HBsAb can be used to predict PVT in CHB patients.

To investigate the clinical value and performance of [18F]AlF-NOTA-FAPI-04 PET/CT in assessing early-stage liver fibrosis in liver transplantation (LT) recipients. A prospective study including 17 LT recipients and 12 chronic Hepatitis B (CHB) patients was conducted. All patients received liver biopsy, transient elastography (TE), and [18F]AlF-NOTA-FAPI-04 PET/CT. On [18F]AlF-NOTA-FAPI-04 PET/CT scans, the liver parenchyma’s maximum standardized uptake values (SUVmax) were measured. The receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic efficacy of [18F]AlF-NOTA-FAPI-04 PET/CT in early-stage liver fibrosis (S1–S2) compared with the diagnostic performance of TE. Among those 29 patients enrolled in this study, 15(51.7

Objective To investigate risk factors for the development of post-transplant diabetes mellitus(PTDM)in pa-tients undergoing orthotopic liver transplantation.Methods We included 293 patients who underwent orthotopic liver transplan-tation at The Affiliated Hospital of Qingdao University from July 1,2017 to January 31,2023.According to whether PTDM oc-curred,the patients were divided into PTDM group(n=66)and non-PTDM group(n=227).Significantly different clinical para-meters between the two groups were included in a multivariable logistic regression model to determine independent risk factors for PTDM.The impact of PTDM on the survival rate of the patients was analyzed using a Kaplan-Meier survival curve.Results The incidence rate of PTDM among the patients was 22.5％.The PTDM group and non-PTDM group differed significantly in age,the percentage of patients with a history of hypertension,preoperative fasting blood glucose level,preoperative serum total choles-terol level,preoperative serum low-density lipoprotein level,the percentage of patients treated with cyclosporine after surgery,and the percentage of patients treated with anti-rejection regimen C(cyclosporine alone or combined with mycophenolate or sirolimus)or D(mycophenolate or sirolimus alone)after surgery(t=-3.191,U=-5.668--2.559,x2=3.922-5.689,P＜0.05).The multivariable logistic regression analysis showed that age＞46 years,a history of hypertension,preoperative fasting blood glucose level＞6.1 mmol/L,preoperative serum low-density lipoprotein level＞3.12 mmol/L,postoperative use of anti-rejection regimen C(cyclosporine alone or combined with mycophenolate or sirolimus)were independent risk factors for the occurrence of PTDM(P＜0.05).The survival curve showed that the occurrence of PTDM significantly decreased the 5-year survival rate of the patients(P＜0.05).Conclusion Age＞46 years,a history of hypertension,preoperative fasting blood glucose level＞6.1 mmol/L,pre-operative serum low-density lipoprotein level＞3.12 mmol/L,and postoperative anti-rejection treatment with cyclosporine alone or combined with mycophenolate or sirolimus are independent risk factors for adult PTDM.

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.

目的 分析肝移植受者术后结直肠腺瘤性息肉(CAP)的发生情况及危险因素.方法 选取肝移植受者77例,并选取同期行结肠镜检查的体检者231例,分析结直肠息肉发生情况及病理检查结果.收集肝移植受者的临床资料,并根据CAP的发生情况,将肝移植受者分为CAP组(28例)和非CAP组(49例),分析肝移植术后发生CAP的危险因素.结果 肝移植受者和体检者结直肠息肉的5年累积发生率分别为43％和34％,CAP的5年累积发生率分别为29％和23％,差异均无统计学意义(均为P>0.05).肝移植受者中,除1例因息肉较多未统计外,其余息肉共计65个,部分受者发现多个息肉.5个体积较小者未送病理,有病理结果的共60个,包括炎性息肉25个,CAP 33个(其中8个伴有低级别上皮内瘤变,3个伴有高级别上皮内瘤变),高分化腺癌2个.Cox模型分析提示肝移植受者术后服用环孢素是发生CAP的独立危险因素.结论 肝移植术后CAP发生风险略有增高,服用环孢素是肝移植受者术后发生CAP的独立危险因素,应重视肝移植受者术后结肠镜检查.

OBJECTIVE:Medication-related osteonecrosis of the jaw (MRONJ) is the main adverse side effect of bisphosphonates (BPs), mainly owing to the inhibitory effect of BPs on osteoclastogenesis. CircRNAs were identified to be an important factor in regulating cellular processes. The aim of this study was to explore the effect of mmu_circ_0001066 on BP-inhibited osteoclastogenesis.MATERIALS AND METHODS:The expression of MRONJ-related miRNA in RANKL-induced RAW264.7 cells treated with BP was analyzed using qRT-PCR analysis. Bioinformatics techniques were applied to screen potential circRNAs. Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were used to examine the effect of mmu_circ_0001066 on osteoclastogenesis. Bioinformatics analysis, luciferase reporter assays, and Western blotting assays were performed to investigate the underlying mechanism.RESULTS:Four MRONJ-related miRNAs were upregulated in BP-treated RAW264.7 cells, and the expression of mmu_circ_0001066 was negatively correlated with those of MRONJ-related miRNAs. Furthermore, the upregulation of mmu_circ_0001066 partially attenuated the inhibitory effect of BP on osteoclastogenesis in RAW264.7 cells. Mechanistically, upregulated miR-16 suppressed osteoclastogenesis and miR-16 inhibitor increased osteoclastogenesis. Furthermore, we have identified that miR-16 is a downstream effector of mmu_circ_0001066.CONCLUSION:Our results suggest that mmu_circ_0001066 played an important role in the BP-mediated suppression of osteoclastogenesis, which lays a foundation for identifying mmu_circ_0001066 as a potential biomarker for MRONJ.

Abstract Aims: To investigate the clinical usefulness and performance of 18F-FAPI PET/CT in assessing early-stage liver fibrosis in liver transplantation (LT) recipients.Methods: A prospective study including 17 LT recipients and 12 chronic Hepatitis B (CHB) patients was performed. All patients received liver biopsy, transient elastography (TE), and 18F-FAPI PET/CT. The maximum standardized uptake values (SUVmax) of the liver parenchyma were recorded on 18F-FAPI PET/CT images. The receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic efficacy of 18F-FAPI PET/CT in early-stage liver fibrosis (S1 ~ S2) compared with the diagnostic performance of TE.Results: Of 29 patients, 15(51.7%) had fibrosis stage 0 (S0), 10(34.5%) had stage 1 (S1), and 4(13.8%) had stage 2 (S2) respectively. The SUVmax of patients with early-stage liver fibrosis were significantly higher than those without liver fibrosis in LT recipients and CHB patients (p=0.004, p=0.02). In LT recipients, a SUVmax cut-off value of 2.0 detected early-stage liver fibrosis with an AUROC of 0.92 (P=0.006) and a Liver Stiffness measurements (LSM) score cut-off value of 8.2 kPa detected early-stage liver fibrosis with an AUROC of 0.80 (P=0.012). In CHB patients, a SUVmax cut-off value of 2.7 detected early-stage liver fibrosis with an AUROC of 0.94 (P<0.001) and a LSM scores cut-off value of 8.4 kPa detected early-stage liver fibrosis with an AUROC of 0.91 (P<0.001).Conclusions: 18F-FAPI PET/CT could be applied to evaluate early-stage liver fibrosis in LT recipients and CHB patients accurately. Compared with TE, 18F-FAPI PET/CT was comparable in detecting early-stage liver fibrosis with the additional advantages in whole-liver evaluation.

目的 肝移植(liver transplantation,LT)术后早期急性肾损伤(acute kidney injury,AKI)的发生是影响患者长期预后的常见问题之一,本研究试图创建一个列线图以精确预测术前肾功能正常的LT受者术后早期AKI的发生.方法 回顾性分析本院2017年7月1日至2020年12月31日期间行LT术后患者369例的临床病历资料,最终纳入349例患者,根据是否发生AKI分为AKI组和非AKI组,通过多元Logistics回归分析确定AKI的独立危险因素,并将其用于创建列线图风险预测模型.通过使用内部验证一致性指数(concordance index,C-index)来评估列线图的效能.结果 AKI在LT术后7 d内发生率为53％(185/349).多元Logistics回归分析显示年龄(OR=2.049;95％CI=1.252～3.352)、BMI(OR=2.041;95％CI=1.251～3.329)、术前γ-谷氨酰转肽酶(γ-glutamyl transpeptidase,GGT)(OR=2.261;95％CI=1.288～3.970)、术后乳酸峰值(OR=2.917;95％CI=1.798～4.733)、腹水(OR=1.874;95％CI=1.104～3.180)、术前白蛋白(OR=0.475;95％CI=0.271～0.832)是LT术后AKI的独立危险因素,在预测LT术后早期AKI的列线图中,其内部验证C-index为0.755,并且校准曲线斜率接近于1表明校准良好.结论 本研究所得列线图在预测肝移植术后早期肾功能不全方面具有较好的临床应用价值.

BACKGROUND:The aim of this study was to test the effectiveness, safety and stability of the 5G communication technology in clinical laparoscopic telesurgery.METHODS:An ultra-remote radical cystectomy (network communication distance of nearly 3000 km) was performed on patient diagnosed with T2N0M0 stage bladder cancer using a domestically produced "MicroHand" surgical robot.RESULTS:The network delay, operative time, blood loss, intraoperative complications, postoperative recovery, and hospitalisation time were recorded. The 5G network was used throughout the operation, with an average total delay of 254 ms. The operation went well and the patient recovered smoothly.CONCLUSIONS:Ultra-remote clinical laparoscopic surgery can be performed safely and smoothly. More importantly, our model can provide insights for promoting the future development of telesurgery in China.

目的:探讨内科知识培训在外科专业学位研究生培养体系中的应用并评价其效果.方法:选取外科专业学位研究生148名为研究对象,进行内科知识培训,通过培训前后调查问卷、会诊单数量统计、质量评价及培训后考核进行培训效果评价.结果:培训后,外科专业学位研究生对内科知识掌握度有所增加(P<0.001);对培训需求有所提高(P<0.001);会诊单数量有所下降,质量有所提高.结论:内科知识培训能有效提高外科专业学位研究生内科疾病诊治能力,补充其课程设置的不足.

Liver transplantation is an effective treatment for patients with various end-stage liver diseases, and the demand of graft livers is increasing. Non-alcoholic fatty liver disease (NAFLD) is getting more and more attention as a chronic liver disease. Recently, the international expert consensus has proposed a new name for NAFLD-metabolic associated fatty liver disease. With the increasing number of liver transplantation, the problems of NAFLD after transplantation have attracted more and more attention. This paper reviews the occurrence, risk factors, measures of prevention and treatment in NAFLD after liver transplantation.

本综述介绍了免疫检查点抑制剂在肝癌肝移植中的研究进展，总结了近几年国内外对肝癌肝移植术后免疫检查点抑制剂药物应用的临床报道，分别从免疫检查点抑制剂的作用机制、临床应用、发生排斥反应的相关因素及机制等方面做了详细描述，以期为临床管理人员制定肝癌肝移植术后诊疗计划提供参考。

红皮病(Erythroderma)是一种病因复杂、 病死率高的全身性皮肤病,表现为全身皮肤广泛的红斑和脱屑,体表受累面积可超过90％[1].红皮病的年发病率约为0.0001％～0.0002％[2].肝移植术后红皮病的临床报道并不多见,且该症的临床诊疗具有其特殊性及一定难度,本文回顾了1例少见的肝移植后新发重度红皮病的临床诊疗经验,报道如下.

目的 探讨乙型肝炎病毒(hepatitis B virus,HBV)相关肝移植(liver transplantation,LT)后停用乙肝免疫球蛋白(hepatitis B immunoglobulin,HBIG)单用替诺福韦(tenofovir disoproxil fumarate,TDF)预防HBV复发的有效性、安全性及经济性.方法 选取我院HBV相关LT患者,将患者分为TDF单药组和恩替卡韦(entecavir,ETV)联合HBIG用药组,收集患者临床及实验室数据并比较两种用药方案的效果、不良反应及用药花费.结果 截止到2019年6月30日,本研究终纳入单药组10例和联用组28例,分别平均随访13.50个月和13.03个月,单药组1例(10.00％)和联用组2例(7.14％)出现乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性复发,所有患者术后乙肝DNA(hepatitis B virus DNA,HBV-DNA)始终为阴性,联用组1例(3.57％)死亡,单药组费用明显低于联用组(490元/月比1952.55元/月,P<0.01).结论 与ETV联合HBIG相比,LT后TDF单药预防HBV复发,具有良好的有效性、安全性和经济性.

Objective:To investigate the clinical efficacy and safety of sorafenib sequential regorafenib in the treatment of recurrence of hepatocellular carcinoma after liver transplantation.Methods:The clinical data of 14 patients with hepatocellular carcinoma who had tumor recurrence after liver transplantation and received sorafenib and regorafenib were collected from the Affiliated Hospital of Qingdao University from February 2014 to September 2020. After the clinical diagnosis of recurrence of liver cancer, sorafenib (400 mg/time, twice a day, oral) was added for treatment. When the disease progressed or the adverse events of sorafenib was not tolerated, sequentially treated with regorafenib (160 mg/time, once a day, oral, continuous medication for 21 days, stop medication for 7 days, every 28 days is a cycle) treatment. The medication was supplemented with symptomatic support treatment, followed up regularly, alpha-fetoprotein (AFP), liver function, immunosuppressive blood concentration, ultrasound or CT and other imaging examinations were monitored, and adverse events were recorded.Results:Among the 14 patients who finally met the inclusion criteria, 12 were males and 2 were females; the median age was 56.5 (40.0-65.0) years. The median interval from tumor recurrence after liver transplantation to initiation of sorafenib was 1.0 (0.1-6.4) months. The median treatment time for sorafenib was 2.7 (0.9-9.2) months, and the median time to progression (mTTP) was 4.4 (0.9-14.1) months. The median time between cessation of sorafenib and initiation of regorafenib was 16.5 (1-366) d; the median treatment time of regorafenib was 9.3 (1.3-20.4) months, the mTTP was 2.8 (1.0-9.7) months, and the median overall survival (mOS) was 20.1 (95%CI 0.7-39.5) months. There were no significant differences in AFP and liver function indexes before and after sorafenib treatment (all P>0.05). AFP increased and serum albumin decreased after treatment, with statistical significance (all P<0.05). ALT, AST and total bilirubin changes had no statistical difference (all P>0.05). Adverse events during the treatment of sorafenib and regofinib included: diarrhea (9 cases and 10 cases), fatigue (9 cases and 6 cases), decreased body mass (3 cases and 2 cases), and hand-foot skin reactions (1 case and 2 cases), respectively. Among them, sorafenib treatment was terminated in 2 cases due to severe diarrhea, and the dosage of regogafenib was reduced in 1 case, and the treatment of regogafenib was discontinued in 1 case due to hand and foot skin reaction, respectively. The other patients had adverse reactions and were tolerated after symptomatic treatment. By September 2020, the median follow-up time was 12.4 (5.6-34.2) months, and a total of 7 patients died, all due to tumor progression after liver cancer recurrence. Of the 7 patients who survived, 3 were discontinued due to lung tumor progression, and 4 were continued with regofinib. The mOS was 14.4 (95%CI 3.4-25.4) months for 14 patients who received sorafenib sequential regolfinib, and the 1-year and 2-year cumulative survival rates were 67.7% and 48.4%, respectively.Conclusion:Sorafenib sequential regorafenib for the treatment of tumor recurrence after liver transplantation of hepatocellular carcinoma has good clinical efficacy and safety, but a larger sample size of research support is still needed.

Hepatitis B virus (HBV) reactivation is one of the common problems faced by HBV-related recipients after liver transplantation. Recently, the application of nucleos(t)ide analogues (NAs) has greatly reduced the recurrence rate of HBV after liver transplantation, and long-term medication has also brought many disadvantages, such as drug resistance, kidney damage. Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) are both high genetic barrier NAs, and clinical applications show that they have good efficacy and tolerability, especially NAs monoprophylaxis have a good application prospect against HBV reactivation after liver transplantation. This article reviews the latest application progress of TDF and TAF after liver transplantation.

肝移植是目前治疗乙型肝炎病毒(HBV)相关终末期肝病最为有效的方法，但肝移植术后出现乙型肝炎复发易损伤移植肝功能，并影响受者的长期存活。尽管乙型肝炎免疫球蛋白(HBIG)和核苷(酸)类似物(NA)的临床应用，可以显著抑制HBV复制并改善受者的长期存活率，而且低剂量HBIG联合NA方案仍然是目前肝移植术后乙型肝炎复发的标准预防方案。然而，近年来，随着高耐药基因屏障NA的出现，肝移植术后NA和(或)短期联合HBIG的单一用药预防方案也取得了良好的临床疗效，本文就肝移植术后单一NA预防乙型肝炎复发的研究进展做一综述。

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.