Liver transplantation is the most effective radical treatment for hepatocellular carcinoma (HCC), especially for patients with HCC complicated by cirrhosis. Since most patients are in an advanced stage of unresectable state when they are present, the preoperative downstaging treatment for liver transplantation in HCC is of great significance for increasing the opportunity for surgery, reducing the dropout rate from the liver transplant waiting list, and thereby lowering the postoperative recurrence rate. Currently, immune checkpoint inhibitor (ICI)-based combination immunotherapy and targeted therapy is the most effective treatment for preoperative downstaging in liver transplantation for HCC. However, the immunoenhancing effects of ICI may increase the risk of post-transplant rejection. Therefore, it is necessary to find a "critical point" that allows ICI to effectively inhibit tumor growth during preoperative downstaging treatment without causing severe rejection after transplantation. This article reviews the latest advances in preoperative ICI treatment protocols, efficacy assessment, indications, contraindications, drug discontinuation timing, and principles of prevention and treatment of rejection in liver transplantation for HCC.

Objective To discuss the perioperative blood transfusion strategy of patients with hereditary coagulation fac-tor deficiency through the perioperative blood coagulation management of a patient with coagulation factor Ⅺ deficiency and hemangioma of knee joint.Methods Coagulation factor activity test and gene test were used to confirm the patients with co-agulation factor Ⅺ antecedent deficiency.Perioperative bleeding risk assessment,thromboela-stogram(TEG)and coagula-tion factors detection were performed to detect the coagulation status of the patients.400 mL fresh frozen plasma was trans-fused before surgery and first day after surgery,200 mL daily for 3 days thereafter.Results The level of APTT was con-trolled from 97.1 s before operation to 36.9 s after operation.There was no obvious bleeding during operation,and the wound healed well after operation.Conclusion In the situation of lack of commercial coagulation factors,transfusion of blood products such as fresh frozen plasma can significantly improve the coagulation function and reduce the risk of intraoperative bleeding in patients with hereditary coagulation factor deficiency during perioperative period.

Objective: To prepare an inactivated hepatitis A vaccine using a attenuated strain of hepatitis A virus (HAV) H2 and to analyze its immunizing dose, so as to provide the reference for development and production of inactivated hepatitis A vaccines. Methods: Human embryonic lung diploid cells (KMB17) were infected with attenuated HAV H2 strain to proliferate the virus, then the cells containing viruses were harvested, extracted and purified. The obtained virus concentrate was prepared into vaccine bulk and test vaccines with 1 280 EU/mL antigen content. Vaccine testing was carried out according to the inactivated hepatitis A vaccine standards specified in the Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). A total of 110 mice were randomly divided into 11 groups, including 5 dose groups (80, 160, 320, 640 and 1 280 EU/dose) of the test vaccine and the reference vaccine, as well as the adjuvant control group. Mice were immunized twice by intraperitoneal injection, their serum HAV antibodies were detected, and the geometric mean titer (GMT) and positive conversion rate of antibodies were analyzed to evaluate the immunising dose of the vaccine. Results: The antigen content and viral titer of the virus harvest solution were 5 120 EU/mL and 8.33 lgCCID50/mL, respectively. The removal rate of foreign protein reached 98.05% and the recovery rate of antigen was 66.25%. The test vaccine met the requirements of Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). The GMTs of HAV antibodies in the test vaccine and the reference vaccine dose groups after the second immunization were more than twice higher than those after the first immunization. Regardless of primary immunization or secondary immunization, the GMTs (log2) of HAV antibodies in the test vaccine groups with doses of 160 EU/dose and above were higher than those in the 80 EU/dose group (all P<0.05), while there was no statistically significant differences between the dose groups of 160 EU/dose and above (all P>0.05). The antibody positive conversion rate of 160 EU/dose and above of the test vaccine was 100.00% after the secondary immunization. Conclusions The inactivated hepatitis A vaccine of attenuated H2 strain tested in this study demonstrates strong immunogenicity in mice, suggesting its potential as a candidate vaccine. The preliminary analysis indicates an immunizing dose of 320 EU/dose for children and 640 EU/dose for adults.

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Objective:To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease.Methods:53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes.Results:As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased ( P<0.05), while the spleen volume gradually increased ( P<0.05). The expression of CD31 and GS gradually increased ( P<0.05), and the expression of Ki67 first increased and then decreased ( P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume ( r=-0.609, P<0.001) and the total liver volume ( r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume ( r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume ( r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume ( r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV ( r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area( r=-0.511, P=0.009). Conclusion:As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.

Objective To understand the distribution characteristics and stroke risk of hospitalized patients in single center atrial fibrillation in traditional Chinese medicine hospitals for guidance in prevention and treatment of atrial fibrillation.Methods A total of 667 clinical diagnosis and treatment data from Guangdong Provincial Hospital of Chinese Medicine,Hainan Hospital from October 2020 to September 2022 in the data filling platform of China Atrial Fibrillation Center through retrospective investigation was collected[including hospitalization information,diagnosis and treatment,demographic information symptoms,European Heart Rhythm Association(EHRA),health assessment].Descriptive epidemiological methods were employed to analyze the distribution characteristics of different populations,and a Logistic regression model was used with CHA2DS2-VASc score as the dependent variable to analyze the risk factors of stroke in men and women with non-valvular atrial fibrillation respectively.Results Among patients with atrial fibrillation,valvular atrial fibrillation accounted for 5.85%(39/667),while non-valvular atrial fibrillation accounted for 94.15%(628/667).Persistent atrial fibrillation was the main type at 65.52%(437/667),with a higher proportion of patients in males than that in females(1.22∶1).The average age of patients was 75.14±11.23 years,mainly aged 71-80 years and 81-90 years,accounting for 33.28%(222/667)and 28.78%(192/667)respectively.Clinical symptoms mainly include palpitations(51.27%)and chest discomfort(45.43%),79.01%(527/667)of patients had EHRA symptom rating below gradeⅡ,while 20.99%(140/667)had ratings above gradeⅢ.The highest incidence of comorbidities of atrial fibrillation was hypertension at 64.62%(431/667),followed by chronic heart failure at 36.43%(243/667).The proportion of high-risk stroke population in the CHA2DS2-VASc score was significantly higher than that of the medium to low-risk stroke population[89.17%(560/628)vs.10.83%(68/628)].In contrast,the proportion of people with low risk of bleeding in the HAS-BLED score was significantly higher than that of people with high risk of bleeding[69.27%(462/667)vs.30.73%(205/667)].A univariate analysis was conducted on 628 patients with non-valvular atrial fibrillation by gender.The results showed that among 279 female patients with CHA2DH2-VASc score≥3 as the dependent variable,univariate analysis showed that there were significant differences in age,hypertension,coronary heart disease,cardiomyopathy,chronic heart failure,cerebrovascular disease,and thyroid disease between the two groups(all P<0.05).A total of 349 male patients with CHA2DH2-VASc score≥2 as the dependent variable,statistically significant differences were showed in age,education level,EHRA and whether had hypertension,coronary heart disease,chronic heart failure,cerebrovascular disease,and thyroid disease(all P<0.05)by univariate analysis.Multivariate Logistic regression analysis showed that the high-risk factors for stroke were age,systolic blood pressure,thyroid disease and cerebrovascular disease in women[female>75 years old:odds ratio(OR)=42.270,95%confidence interval(95%CI)was 9.130-195.800;systolic blood pressure>160 mmHg(1 mmHg≈0.133 kPa):OR=3.530,95%CI was 1.420-8.760,and thyroid disease:OR=0.140,95%CI was 0.040-0.460,cerebrovascular disease:OR=9.400,95%CI was 2.130-41.440;all P<0.05].While age,education level,systolic blood pressure,chronic heart failure,cerebrovascular disease,and thyroid disease in men were high-risk factors(male>75 years old:OR=81.270,95%CI was 27.730-238.210;education level:OR=0.250,95%CI was 0.120-0.530;systolic blood pressure>160 mmHg:OR=14.110,95%CI was 7.250-27.460;patients with chronic heart failure:OR=23.780,95%CI was 7.850-71.970;thyroid disease:OR=0.240,95%CI was 0.110-0.540;patients with cerebrovascular disease:OR=0.580,95%CI was 0.360-0.940;all P<0.05).Conclusions The proportion of male hospitalized patients with atrial fibrillation at Guangdong Provincial Hospital of Chinese Medicine,Hainan Hospital is greater than that of females.The majority of these patients are elderly,with an average age higher than recently reported.They face a more prominent of stroke,especially those with high blood pressure,chronic heart failure,cerebrovascular disease,and thyroid disease.It is crucial to strengthen targeted prevention and treatment efforts in this population.

OBJECTIVE: To analyze the accuracy of prosthesis size selection in Naton robot-assisted medial unicondyle knee arthroplasty by comparing the actual prosthesis size used during operation and the preoperative planning. METHODS: The clinical data of 100 patients (110 knees) who underwent Naton robot-assisted medial unicondylar knee arthroplasty between June 2023 and July 2024 was retrospectively analyzed, including 47 knees on left side and 63 knees on right side. There were 37 males (40 knees) and 63 females (70 knees) with a mean age of 65.4 years (range, 59-71 years). Body mass index was 22.2-28.6 kg/m ² (mean, 25.4 kg/m ²). The disease duration ranged from 1 to 8 years (mean, 3.4 years). Preoperative planning was performed by Naton robotic surgical system based on lower limb CT data. The final prosthesis size after osteotomy was recorded and compared with the preoperative plan to analyse whether it was consistent with the preoperative plan, as well as the situation of knee flexion and extension gaps (<0.5 mm, >2.0 mm) corresponding to the different models of prostheses. RESULTS: During operation, 5 patients (5 knees) were treated with traditional UKA due to mechanical arm failure, software obstacles, significant bone amputation bias, or loose reference frame, and were excluded from the final analysis. The remaining 95 patients (105 knees) successfully received Naton robot-assisted surgery, and no related complications occurred. The prosthesis size was consistent with the preoperative plan in 101 knees (96.2%) on the femur side, 100 knees (95.2%) on the tibia side, and 97 knees (92.4%) on both femur and tibia sides. The prosthesis size was inconsistent in 3 cases (2.86%) on the femur side alone, 4 cases (3.81%) on the tibial side alone, and 1 case (0.95%) on both femur and tibial sides. Among the prostheses with different models, the flexion and extension gaps were less than 0.5 mm in 3 knees, the flexion gap was less than 0.5 mm and the extension gap was more than 2.0 mm in 3 knees, and the flexion gap was more than 2.0 mm and the extension gap was less than 0.5 mm in 2 knees. CONCLUSION The accuracy of prosthesis size selection for Naton robot-assisted medial unicondylar knee arthroplasty is relatively high.
Humans ; Arthroplasty, Replacement, Knee/instrumentation* ; Female ; Male ; Middle Aged ; Aged ; Knee Prosthesis ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Prosthesis Design ; Knee Joint/surgery* ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular

Objective To analyze the population distribution pattern of inpatients in the China Atrial Fibrillation Center of Hainan Traditional Chinese Medicine Hospital to guide clinical diagnosis and treatment.Methods Clinical diagnosis and treatment(including hospitalization information,diagnosis and treatment,symptoms,health assessment,physical examination,examination,testing,therapeutic drugs),European Heart Rhythm Association(EHRA)symptom score,CHA2DS2-VASc score for predicting stroke risk stratification in atrial fibrillation,HAS-BLED score for predicting bleeding risk in anticoagulated were collected from Hainan Traditional Chinese Medicine Hospital from October 2020 to September 2022 in the data filling platform of China Atrial Fibrillation Center through retrospective investigation.The normal reference values of various examination indicators set for analysis are heart rate 60-100 beats/min,QTc interval <480 ms for males and<470 ms for females,ejection fraction(EF)0.50-0.75 for B-ultrasound,left atrial anteroposterior diameter <35 mm,left ventricular end-diastolic diameter(LVEDD)<55 mm for males and <50 mm for females,no left atrial thrombosis,International normalized ratio(INR)0.85-1.20,brain natriuretic peptide(BNP)0-100 ng/L,N-terminal pro-brain natriuretic peptide(NT-proBNP)0-125 ng/L in cardiology,0-250 ng/L in non cardiology.Results Among 667 patients,there were 39 cases of valvular atrial fibrillation and 628 cases of non valvular atrial fibrillation.The completion rate of various diagnostic(physical examination/examination/testing)indicators was 19.94％-100.00％.Statistically significant differences were showed in every EHRA symptom score,HAS-BLED score,BMI,hypertension,heart rate,EF,left atrial diameter,LVEDD,left atrial thrombus,INR(Warfarin user),BNP,NT-proBNP and atrial fibrillation treatment methods(all P<0.01).No statistically significant difference was shown in CHA2DS2-VASc scores for each gender,QTc and NT-proBNP(all P>0.05).409 patients were treated with antiarrhythmic drugs,with a treatment rate of 61.32％.Statistically significant difference was showed in the proportion of medication use among different populations with heart rates of<60,60-100,and ≥100 beats/min,respectively[46.51％(20/43)vs.54.60％(196/359),72.83％(193/265),P<0.01],and the highest drug usage rate was β receptor blockers.Statistically significant difference was shown in the use rate of different antiarrhythmic drugs(P<0.01).There were 342 patients treated with anticoagulant therapy,with a treatment rate of 51.27％,the treatment rate of valvular atrial fibrillation was significantly higher than that of non-valvular atrial fibrillation[84.62％(33/39)vs.49.20％(309/628)],with a statistically significant difference(P<0.01).No statistically significant difference was shown in treatment rates between individuals with CHA2DS2-VASc scores of ≥2 for males and ≥3 for females of non-valvular atrial fibrillation,and between individuals with CHA2DS2-VASc scores of <2 for males and <3 for females,as well as between individuals with HAS-BLED scores of ≤2 and ≥3 for treatment rates(all P>0.05).Statistically significant differences were shown in the usage rates of different anticoagulants,antiplatelet aggregation drugs,blood lipid control(statins)drugs,and blood pressure control drugs(all P<0.01).The types of medication used for blood pressure control are angiotensin converting enzyme inhibitor(ACEI),angiotensin Ⅱ receptor blocker(ARB),calcium channel blocker(CCB),β receptor blockers and diuretics.The single drug composition ratio of the medication plan was the highest(39.75％),and the diuretics composition ratio of drug use was the highest(48.00％),with statistically significant differences(all P<0.01).Conclusions The operation of the Atrial Fibrillation Center of Hainan Traditional Chinese Medicine Hospital has covered all clinical diagnosis and treatment projects,and the treatment plan is consistent with the guidelines.At present,the control of blood pressure,BMI,and heart rate of hospitalized patients needs to be further strengthened,especially the proportion of high-risk people with stroke,and there is insufficient anticoagulation treatment.The training of the guidelines should be improved to promote standardized treatment.

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Objective:To explore the effect of pre-transplant immunotherapy on the prognosis of transplant recipients with hepatocellular carcinoma(HCC).Methods:From June 2018 to September 2021, retrospective analysis was conducted for clinical data of 19 HCC-liver transplant recipients receiving pre-transplant immunotherapy in affiliated Huashan Hospital of Fudan University. Pre-transplant immunotherapy regimen, adverse reactions, post-transplant acute rejection, tumor recurrence and metastasis and other complications were recorded. According to the preoperative tumor imaging and the changes of alpha-fetoprotein level, tumor change during recipient waiting period was judged by the mRECIST standard. According to whether or not there was partial tumor remission, they were divided into two groups of non-remission( n=13)and remission( n=6). Postoperative conditions of two groups were compared. Kaplan-Meier method was used for calculating the survival rate of recipients after transplantation and survival curve and Log-rank test utilized for comparing the recurrence-free and overall survival rates of recipients at 1 and 2 years post-operation. Results:A total of 19 liver transplant recipients received immunotherapy plus targeted and transcatheter arterial chemoembolization(TACE) before transplant. In non-remission group, tumor was stable( n=9)and progressive( n=4); 6 cases in remission group had tumor partial remission. Two recipients in non-remission group were pathologically confirmed by liver biopsy to have acute rejection(2/19, 10.5%)and both recovered after glucocorticoid + rATG and glucocorticoid therapy. In non-remission group, 2 patients died from septic shock post-operation. Among 3 patients of tumor recurrence and metastasis post-operation, 2 cases survived with tumor and 1 died after tumor recurrence and metastasis. In remission group( n=6), none had postoperative tumor recurrence and metastasis. The recurrence-free survival rates of non-remission group recipients at 1 and 2 years post-operation were 76.9% and 76.9% and recurrence-free survival rates in remission group were 100% and 100% respectively and inter-group difference in RFS was not statistically significant( χ2=1.468, P=0.226). The overall survival rates of recipients in non-remission group at 1 and 2 years post-operation were 76.9% and 76.9% respectively. And recipients in remission group were 100% and 100% respectively and no statistically significant inter-group difference existed in OS( χ2=1.292, P=0.256). Conclusions:Without a significantly higher risk of acute rejection after transplant, immunotherapy may be an effective option for bridging treatment before liver transplantation for HCC. And it remains necessary to expand the sample size for verifications and supports.