Objective:To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs).Methods:Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ2 test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results:This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ2=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ2=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ2=20.298, P < 0.001, 54.9% vs. 85.7%, χ2=17.917, P < 0.001;40.2% vs. 55.8%, χ2=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ2=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion:The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

Objective:To explore the levels of programmed death receptor 1 (PD-1) and lymphocyte activating gene 3 (LAG-3) in the immune microenvironment of diffuse large B-cell lymphoma (DLBCL), their relationship with clinicopathological features, and their impact on prognosis.Methods:The tumor tissue sections and formaldehyde fixed paraffin embedded tissues from 174 DLBCL patients diagnosed at the First Affiliated Hospital of Xinjiang Medical University from February 2012 to August 2017 were retrospectively collected. The tissue chips were prepared, and the immunohistochemistry (IHC) method was used to detect the expressions of PD-1 and LAG-3 proteins in tumor infiltrating lymphocytes (TIL) of tissue chips [including whether they were positive (positive for IHC score 1-9 points, negative for 0 point) and expression level (high expression was 4-9 points on IHC score, low expression was 0-3 points)]. The relationship between the expression levels of PD-1 and LAG-3 and the clinicopathological characteristics of patients was analyzed. Spearman correlation coefficient was used to analyze the correlation between the expression levels of PD-1 and LAG-3. Kaplan-Meier method was used to draw overall survival (OS) and progression free survival (PFS) curves of patients with different expression levels of PD-1 and LAG-3, and log-rank test was used for comparison between the groups. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of OS and PFS in patients.Results:Of the 174 DLBCL patients, 95 (54.6%) were male and 79 (45.4%) were female; the median age was 60 years old (5-87 years old). The proportions of patients with PD-1 and LAG-3 positive in TIL of tumor tissues were 79.3% (138/174) and 78.8% (137/174), and the proportions of patients with high expression were 35.6% (62/174) and 37.9% (66/174), respectively. Among patients with bone marrow involvement, the proportion of patients with high expression of PD-1 [62.5% (15/24) vs. 32.5% (39/120), P= 0.006], the proportion of patients with high expression of LAG-3 [54.2% (13/24) vs. 32.5% (39/120), P= 0.050] were higher than those without bone marrow involvement. The expression levels of PD-1 and LAG-3 were not associated with gender, age, clinical stage, international prognostic index score, functional status (PS) score, lactate dehydrogenase level, whether there were B symptoms, whether it was intranodal, tumor length, whether it was germinal center B cell type, number of extranodal involvement sites, and whether it was treated with R-CHOP regimen (all P > 0.05). There was a positive correlation between PD-1 and LAG-3 expression levels in TIL of tumor tissues ( r = 0.202, P = 0.008). Multivariate Cox regression analysis showed that PS score (>2 points vs. ≤2 points: HR = 5.458, 95% CI 2.082-14.307, P = 0.001), R-CHOP regimen treatment (no vs. yes: HR = 2.181, 95% CI 1.086-4.379, P = 0.028) were independent influencing factors of OS, and PS score (>2 points vs. ≤2 points: HR = 3.913, 95% CI 1.579-9.698, P = 0.003), R-CHOP regimen treatment (no vs. yes: HR = 2.609, 95% CI 1.412-4.819, P = 0.024), LAG-3 expression level (low expression vs. high expression: HR = 0.531, 95% CI 0.283-0.995, P = 0.048) were independent influencing factors of PFS. There were no statistical differences in PFS and OS between patients with high and low PD-1 expression levels in TIL (both P > 0.05). PFS and OS in patients with high LAG-3 expression were worse than those in patients with low expression (both P < 0.05). OS in patients with high expressions of PD-1 and LAG-3 was worse than that in patients with low expressions of PD-1 and LAG-3 ( P = 0.044). Conclusions:The expression levels of PD-1 and LAG-3 in TIL of DLBCL patients' tumor tissues are related to bone marrow involvement, which are not related to most other clinicopathological features, and the prognosis of patients with high expressions of PD-1 and LAG-3 is poor.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Objective To investigate the frequency and location of cerebral microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) to understand the imaging and clinical features of the disease.Methods Cranial magnetic resonance imaging and susceptibility-weighted imaging were assessed in seven symptomatic CADASIL patients in People's Hospital of Zhengzhou University from 2014 to 2017.Imaging features and clinical significance of these patients were analyzed retrospectively.Results The seven patients were diagnosed by Notch3 gene detection.Mutations were found in exon 11 in four cases,and in exon 4 in three cases.All the seven patients with CADASIL had cerebral microbleeds,the number of which was 108 (4-36).The number of cerebral microbleeds was found to be higher in cortico-subcortical region than in any other regions.One of CADASIL patients with cerebral microbleeds had intracerebral hemorrhage located in external capsule.The patient with intracerebral hemorrhage had hypertension and multiple cerebral microbleeds.Conclusions Cerebral microbleeds are common imaging characteristics in symptomatic CADASIL,most of which locate in cortico-subcortical region.Cerebral hemorrhage is one of the clinical manifestations of CADASIL patients.

Objective: To compare different specimen types of lung adenocarcinoma in the detection of epidermal growth factor receptor (EGFR) gene and to correlate EGFR mutations with patient clinical features. Methods: One hundred lung adenocarcinoma cases were collected from June to December in 2015, at the First Affiliated Hospital of Xinjiang Medical University.Of the 100 lung adenocarcinoma samples, 43 were male and 57 were female. The age was from 40 to 88 years old, and the average age was 66 years. One hundred lung adenocarcinoma cases were divided equally into two groups. Mutation analysis of EGFR gene by real-time PCR was performed using biopsied tissue and paired blood samples in one group (n=50) and using pleural effusion and paired blood samples in the other group (n=50). Results: The mutation rate of EGFR gene in biopsy samples was 54% (27/50) , higher than that of blood samples (46%, 23/50), but without statistical differences (χ²=0.640, P=0.424). In contrast, mutation rate of EGFR gene in pleural effusion samples (42%, 21/50) was higher than that of blood samples (34%, 17/50), but without statistical differences(χ²=0.679, P=0.409). Two patients had EGFR mutation detected in paired blood samples but not in the corresponding biopsy samples, and four patients had EGFR mutation detected in pleural effusion samples but not in their paired blood samples. The mean progression-free survival of patients with detectable EGFR mutation were 9.5 months (tissue samples), 8.6 months (pleural effusion) and 8.5 months (blood). However, there was no statistical difference. Conclusions Blood samples may be used to assess EGFR mutations for patients with lung adenocarcinoma. However, further studies are needed to improve the sensitivity and accuracy in the detection of EGFR mutations using blood samples.

Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels. Results: There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant (P=0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ²=7.648, P=0.006) at mRNA level. Conclusion The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.

Objective To explore the correlation between verbal memory and working memory in patients with alcohol dependence (AD).Methods A total of 40 patients with AD and 40 health controls were included in this study.N-back task was used to evaluate the verbal working memory.20 sets of phrases were used to evaluate long-term verbal memory.Results Correct number of verbal memory in AD group ((5.15±0.92)times) was lower than that of HC group ((7.35±3.07) times) after one-week baseline test,and the difference was statistically significant (t=4.344,P＜ 0.01).Compared with HC group ((1 436.37±192.50) ms,(1.08±0.89) times,(4.00±0.85) times,respectively),AD group((1 535.40± 192.50) ms,(1.90± 1.57)times,(2.60± 1.39)times) showed significantly impaired reply reaction time of 2-back,error number of 1-back and 2-back (t=-2.112,P=0.038;t=-2.899,P=0.005;t=-5.433,P＜0.01).The error number of 2-back task in AD group was negative correlated with verbal memory after one-week baseline test (r=-0.427,P=0.006).Conclusion The verbal memory is impaired in AD patients.Long-term verbal memory damage have a certain correlation with working memory.

Objective To investigate the expression of Notch4 protein and to analyze its correlation with the clinical parameters and the microvessel dentisty in renal cell carcinoma. Methods The expression of Notch4 was examined in 60 cases of renal cell carcinoma and the para-carcinoma tissue by SP immunohistochemical stain-ing ,and CD34 detection was used for counting microvessel density. Statistical analysis was performed to reveal the correlation with clinicopathological parameters ,microvessel density and prognosis. Results The positive rate of Notch4 protein expression was 75%(45/60)in para-carcinoma tissue,and was 43.3%(26/60)in renal cell car-cinoma,with significant difference on tumor grade and Lymph node metastasis(P<0.05). The microvessel densi-ty in Notch4 positive tissues was significant lower than that in the negative samples(P<0.05). The survival time of patients with Notch4 positive expression was significantly longer than that of patients with Notch4 negative expres-sion(P<0.05). Conclusion Notch4 protein plays an important role in the development of renal cell carcinoma. Notch4 expression might both attenuate the malignant biological characteristics and suppress the angiogenesis dur-ing tumor development.

Objective To investigate the changes of hemodynamics and cardiac function in pediatric living donor liver transplantation (LDLT).Methods 50 cases of pediatric living donor liver transplantation in our hospital from January 2016 to January 2017 were collected.The hemodynamics was monitored by Mostcare with the radial artery.Acquisition of heart rate (HR),mean arterial pressure (MAP),peripheral vascular resistance index (SVR/SVRI),stroke volume / stroke index (SV/SVI),cardiac output (CO/CI),cardiac index / stroke volume variability (SVV),dp/dtmax (cardiac contractility),cardiac cycle efficiency (CCE) at the moment of the start of operation(T0),before occlusion of the inferior vena cava (T1),immediately after occlusion of the inferior vena cava (T2),anhepatic phase 30 min (T3),immediately after reperfusion(T4),neohepatic phase 5 min (T5),30 min (T6) and 60 min (T7).Results There were no significantly hemodynamic fluctuations before occlusion of the portal vein.At T3,the increased of MAP,CI,SVRI (T3 vs T0,P＜0.05),while CCE decreased significantly (T3 vs T0,P＜0.05);MAP,SVRI,lower HR,CI and dp/dtmax have different degrees of liver T4,but the change was not significant.SVV fluctuated in the anhepatic phase at 11％ ～ 15％,maintained in the new liver stage at 12％ ～ 15％,but fluctuated slightly.Conclusion Mostcare can be used to monitor the hemodynamic and cardiac function changes in pediatric living donor liver transplantation,but the reasons for the change of the monitoring indicators and the significance of guiding the perioperative treatment need to be further studied.

Objective: To investigate the point mutation of epidermal growth factor receptor (EGFR) gene and clinicopathologic characteristics in patients with non-small cell lung cancers(NSCLC)of Xinjiang region. Methods: Five-hundred and eighty-two cases of paraffin-embedded tissue in patients with NSCLC were collected between January 2013 and December 2015 in the First Affiliated Hospital of Xinjiang Medical University. The DNA was extracted from these tissues by Qiagen kit, to test thirty-two mutations in EGFR exons 18, 19, 20 and 21 using fluorescent quantitative qRT-PCR technology by TaqMan probe; the clinicopathologic features of patients were analyzed according to the mutation status of EGFR. Results: There were 173 cases with EGFR gene mutation in 582 cases of paraffin-embedded tissue in patients with NSCLC, and the mutation rate was 29.7%(173/582). There were statistical difference in female patients (50.5%, 98/194), no history of smoking(47.3%, 96/203), high differentiation(6/9), adenosquamous carcinoma(6/11), peripheral location (34.9%, 88/252), and surgical specimens(38.2%, 83/217), respectively (P<0.05). Multiple factors Logistic analysis showed that gender, degree of differentiation, and pathologic types had statistical differences to EGFR when α=0.05. There were no statistical differences between other variants. Conclusions There are higher rate EGFR gene mutation in women patients, non-smokers, and well-differentiated, adenocarcinoma. Gender, degree of differentiation and pathological patterns are independent influencing factors on EGFR mutation status.