[摘 要] 靶向治疗和免疫治疗常作为晚期肝细胞癌的系统性抗肿瘤方案。然而，受到多种因素的影响，如肿瘤微环境、细胞信号的转导通路、药物转运等因素的影响，晚期肝细胞癌的患者在治疗时往往出现不同程度的原发性和获得性耐药，患者长期获益有限。自IMbrave150试验发现靶向联合免疫治疗方案优于单药治疗后，有效改善了过去单药治疗耐药所产生的生存获益受限，而获得性耐药的解决方案仍受限于缺乏统一标准、病例难收集、差异基因较少等因素。本文综述目前众多正在进行的临床试验，希望为克服肝细胞癌耐药问题提供参考。

Hepatolenticular degeneration is kind of an autosomal recessive genetic disease with diverse, complex and non-specific clinical manifestations, high misdiagnosis rate, rapid disease progression, poor drug treatment effect, and high mortality. It is one of the rare several genetic metabolic diseases in clinic that could be cured by liver transplantation method. Liver transplantation provides healthy P-type ATP enzyme through the donor liver, which can correct its genetic defects, improve copper metabolism disorders, relieve clinical symptoms, improve the quality of life, and improve the survival rate of patients. Liver transplantation is playing an increasingly important role as an important means to treat hepatolenticular degeneration. With the rapid development of partial living donor liver transplantation, auxiliary liver transplantation, domino-assisted liver transplantation and cross-assisted domino liver transplantation, a new way has been provided for patients with hepatolenticular degeneration, alleviating the problem of donor liver shortage and shortening the waiting time of recipients, which has certain clinical value and development prospects. In this paper, a review of the research progress in the treatment of hepatolenticular degeneration with liver transplantation was made with reference to the relevant literature at home and abroad.

Objective:To investigate the efficacy of microscopic decompression in degenerative lumbar spinal stenosis (DLSS) under single percutaneous tubular retractor system.Methods:A retrospective analysis was performed; 117 DLSS patients with imaging manifestations as non-segmental lumbar instability, admitted to Department of Neurosurgery, 900 th Hospital of PLA Joint Logistics Team from October 2018 to April 2023 were enrolled consecutively. These patients failed in strict conservative treatment and then changed to posterior lumbar spinal canal and nerve root decompression by microscopy and percutaneous tubular retractor system. These patients were followed up for 6-50 months. Pain visual analogue score (VAS) and lumbar Oswestry dysfunction index (ODI) were recorded and results of X-rays, CT and MRI of lumbar spines were analyzed 1 d before and 1 week after decompression and at the last follow-up. Modified MacNab criteria were used to evaluate the efficacy at the last follow-up. Results:Among the 117 patients, unilateral laminectomy for unilateral decompression was performed in 56 patients (47.9%) and unilateral laminotomy for bilateral decompression in 61 (52.1%). Single segment decompression was performed in 109 patients (93.2%) and double segment decompression in 8 (6.8%). Dural sac rupture occurred in 4 patients (3.5%), and immediate occlusion was given; no cerebrospinal fluid leakage was noted after decompression. All patients did not experience obvious nerve damage during decompression or intervertebral infection/lumbar instability after decompression. After 18 (13, 24) months of follow-up, VAS scores of the patients at the last follow-up decreased from (5.96±0.85) 1 d before decompression and (1.75±0.61) 1 week after decompression to (1.01±0.59), and lumbar ODI decreased from (63.22±8.33)% 1 d before decompression and (17.66±5.20)% 1 week after decompression to (10.64±3.44)%, with significant differences ( P<0.05). At the last follow-up, modified MacNab criteria indicated 46 patients (39.3%) as excellent, 66 (56.4%) as good, 3 (2.6%) as fair, and 2 (1.7%) as poor, with an excellent/good therapeutic rate of 95.7%. Conclusion:For surgical treatment of DLSS patients without evidenced preoperative spinal instability, personalized unilateral or bilateral spinal canal decompression under microscope by combiningsingle percutaneous tubular retractor system can effectively reduce surgical trauma and achieve satisfactory surgical results.

Objective:To compare the morphological differences of psoas major muscles between patients with lumbar disc herniation (LDH) of lower limb pain and lumbocrural pain based on CT imaging data.Methods:Sixty patients with LDH admitted to Department of Neurosurgery, 900 th Hospital of PLA Joint Logistic Team from January 2012 to February 2023 were included. According to clinical symptoms, they were divided into lower limb pain group and lumbocrural pain group ( n=30). 3D CT images of the psoas major muscles in the 2 groups were reconstructed; the longest transverse axis perpendicular to the longitudinal axis of the psoas major muscle was chosen as the cross-sectional area, and the maximum psoas major muscle cross-sectional area was calculated; maximum psoas major muscle cross-sectional area index (PI max) was defined as ratio of maximum psoas major muscle cross-sectional area and L 5 vertebral cross-sectional area. PI max difference between lower limb pain group and lumbocrural pain group was compared; PI max difference among patients with different pain degrees (visual analog scale [VAS] scores) or pain courses was further compared in both lower limb pain group and lumbocrural pain group. Pearson correlation was used to analyze the correlations of PI max with pain degree and pain course in the 2 groups. Results:PI max in lower limb pain group was significantly larger than that in lumbocrural pain group (0.62±0.05 vs. 0.54±0.04, t=7.320, P<0.001). PI max in patients with severe pain from both lower limb pain group and lumbocrural pain group was significantly smaller than that in patients with moderate pain (0.61±0.05 vs. 0.65±0.04, t=2.422, P=0.022; 0.53±0.03 vs. 0.58±0.04, t=3.502, P=0.002). PI max in patients with short pain course from both lower limb pain group and lumbocrural pain group was significantly larger than that in patients with long pain course (0.64±0.05 vs. 0.59±0.04, t=2.570, P=0.016; 0.57±0.04 vs. 0.53±0.03, t=2.941, P=0.007). Pearson correlation showed that PI max was negatively correlated with pain degree and pain course in LDH patients from both groups ( P<0.05). Conclusion:Atrophy of psoas major muscles in LDH patients is aggravated with increased pain degree and pain course.

Objective To investigate the MRI characteristics of subventricular zone(SVZ)-associated isocitrate dehydrogenase(IDH)wild-type glioblastoma(GBM)and their correlations with Ki-67 expression and O6-methylguanine-DNA methyltransferase(MGMT)promoter methylation status.Methods A retrospective analysis was conducted on data of 78 patients with IDH wild-type GBM who underwent surgery and received pathological confirmation.Preoperative MRI contrast-enhanced T1 WI sequences were used to assess SVZ involvement,and postoperative molecular testing of tumor markers,including Ki-67 expression and MGMT methylation status,was utilized to categorize the patients accordingly.Results The SVZ involved(+)group(P＜0.001)and the MGMT(+)group(P=0.036)exhibited significantly larger tumor volumes.There were no significant differences between the groups in terms of gender,age,left/right hemispheric lateralization,or specific brain lobe distribution.There was no significant association between Ki-67 expression levels,MGMT methylation status,and SVZ involvement,respectively.Conclusion The SVZ(+)group and the MGMT(+)group demonstrates a wider range of tumor invasion.

The limitations of endovascular repair technology for organ arterial injury at the present stage were analyzed,and an endovascular repair device for organ arterial trunk injury was designed to make up for the shortcomings of the existing technology and improve the success rate of treatment.The new balloon injection device is mainly used for the repair of organ arterial trunk injury,which has good passing ability,can effective repair wound and hemostasis,and protect organ function.In clinical practice,it provided a new treatment method for visceral artery trunk injury with limited use of conventional endovascular treatment techniques and no open surgery opportunity.This device can effectively solve the problems of organ dysfunction caused by arterial embolization in the case of arterial trunk injury,and limited by the degree of tube tortuous in the case of stent isolation surgery.

Objective:To explore the effects of hypoxia on traumatic brain swelling (TBS) in rats with acute subdural hematoma (ASDH).Methods:Forty-five SD rats were divided into 5 groups according to the random number table method, with 9 rats in each group: sham surgery normal oxygen group which underwent sham surgical procedures and were placed in a closed container with ventilation, sham surgery hypoxia group which underwent sham surgical procedures and were placed in a closed container with oxygen volume fraction of 8% for hypoxia induction, ASDH normal oxygen group which made into the ASDH model and placed in a closed container with ventilation, ASDH hypoxia group were made into the ASDH models and placed in a closed container with oxygen volume fraction of 8% for hypoxia induction, and ASDH hypoxia+oxygen inhalation group which inhaled oxygen continuously with oxygen volume fraction of 40% after being made into the ASDH models and induced for hypoxia. Six rats were selected from each group immediately after the modeling and craniotomy was performed to observe the brain swelling during the surgery and evaluate the degree of TBS. Microvascular blood flow was observed by laser speckle imaging system before modeling, before craniotomy, and immediately after craniotomy. The remaining 3 rats in each group were killed directly after modeling and brain tissue specimens were collected. The expression levels of pericellular protein α-smooth muscle actin (α-SMA) and platelet-derived growth factor receptor-β (PDGFR-β) at 0, 30 and 60 minutes after modeling were detected through Western blot analysis. The expression levels of α-SMA, PDGFR-β and microvascular marker platelet-endothelial cell adhesion molecule 31 (CD31) at 0 minute after modeling were tested through immunofluorescent staining.Results:No brain bulge was observed in the sham surgery normal oxygen group. The height of brain bulge in sham surgery hypoxia group was 0.5(0.0, 1.0)mm, with no significant difference from that in the sham surgery normal oxygen group ( P>0.05); it was 2.2(2, 2.5)mm in the ASDH normal oxygen group, significantly higher than that in the sham surgery normal oxygen group and sham surgery hypoxia group ( P<0.01), it was 3.1(2.9, 3.2)mm in the ASDH hypoxia group, significantly higher than that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.01); it was 2.8(2.7, 2.9)mm in the ASDH hypoxia+oxygen inhalation group, not statistically different from that in the ASDH hypoxia group ( P>0.05), but significantly increased compared with that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.01). Before modeling, before craniotomy and after craniotomy, the microvascular blood flow was 224.2±49.7, 224.8±50.3, 225.1±50.3 respectively in the sham surgery normal oxygen group and 224.7±43.7, 220.9±45.9, 221.8±45.5 respectively in the sham surgery hypoxia group, with no significant difference between the two groups ( P>0.05); it was 226.5±52.7, 173.4±40.7, 172.0±40.7 respectively in the ASDH normal oxygen group, significantly decreased compared with that in the sham surgery normal oxygen group and sham surgery hypoxia group ( P<0.05); it was 225.7±46.4, 131.4±23.6 and 131.0±23.5 respectively in the ASDH hypoxia group, significantly decreased compared with that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.05); it was 226.2±56.1, 132.6±21.7 and 131.7±21.9 respectively in ASDH hypoxia+oxygen inhalation group, significantly decreased compared with that in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.05), with no significant difference from that in the ASDH hypoxia group ( P>0.05). At 0, 30 and 60 minutes after modeling, the expression levels of α-SMA and PDGFR-β were 0.70±0.02, 0.67±0.01, 0.55±0.05 and 0.65±0.03, 0.56±0.03 and 0.59±0.02 respectively in the sham surgery normal oxygen group and were 0.63±0.04, 0.60±0.01 0.55±0.05 and 0.62±0.01, 0.51±0.01 and 0.60±0.02 respectively in the sham surgery hypoxia group, with no significant difference between the two groups ( P>0.05); they were 0.88±0.06, 0.87±0.05, 0.82±0.03 and 0.85±0.03, 0.85±0.03, 0.88±0.04 respectively in the ASDH normal oxygen group, significantly higher than those in the sham surgery normal oxygen group and sham surgery hypoxia group ( P<0.01); they were 1.19±0.08, 1.10±0.10, 0.97±0.04 and 1.04±0.06, 1.19±0.07, 1.27±0.08 respectively in the ASDH hypoxia group, significantly higher than those in sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group ( P<0.05 or 0.01); they were 1.20±0.07, 1.10±0.04, 0.96±0.04 and 1.04±0.05, 1.15±0.11, 1.20±0.07 respectively in ASDH hypoxia+oxygen inhalation group, significantly higher than those in sham surgery normal oxygen group, sham surgery normal group and ASDH normal oxygen group ( P<0.01), but with no significant difference from those in ASDH hypoxia group ( P>0.05). At 0 minute after modeling, the fluorescence expression of α-SMA and PDGFR-β was weaker in the sham surgery normal oxygen group and the fluorescence expression of CD31 was stronger. There was no significant difference in the fluorescence expressions of α-SMA, PDGFR-β and CD31 between the sham surgery hypoxia group and sham surgery normal oxygen group. The fluorescence expressions of α-SMA and PDGFR-β in the ASDH normal oxygen group were stronger than those in the sham surgery normal oxygen group and sham surgery hypoxia group, while the fluorescence expression of CD31 was weaker. The fluorescence expressions of α-SMA and PDGFR-β in ASDH hypoxia group were stronger than those in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group, while the fluorescence expression of CD31 was weaker. The fluorescence expressions of α-SMA and PDGFR-β in the ASDH hypoxia+oxygen inhalation group were stronger than those in the sham surgery normal oxygen group, sham surgery hypoxia group and ASDH normal oxygen group, while the fluorescence expression of CD31 was weaker, with no significant difference from the fluorescence expressions of α-SMA, PDGFR-β and CD31 in ASDH hypoxia group. Conclusions:Hypoxia in ASDH rats will stimulate pericytes contraction, which causes cerebral microcirculatory disturbance, thus leading to TBS. Short-term inhalation of oxygen of medium concentration cannot dilate pericytes or microcirculation vessels, with no obvious effect on improving the conditions of TBS.

Objective:To study the predictive role of tumor burden score (TBS) for tumor recurrence after radical resection in patients with hepatocellular carcinoma (HCC).Methods:Clinical data of 202 patients with HCC undergoing radical surgery at the 900th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army, between January 2015 and December 2017 were retrospectively analyzed, including 128 males and 74 females, aged (53.66±11.93) years old. The receiver operating characteristic (ROC) curve was used to assess the accuracy of TBS in predicting postoperative tumor recurrence. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors influencing postoperative tumor recurrence. A nomogram was established and validated using calibration curves and the C-index. Kaplan-Meier survival analysis was utilized to compare survival differences between the two patient groups.Results:The area under the ROC curve for TBS in predicting postoperative tumor recurrence in HCC patients was 0.779 (95% CI: 0.717-0.842), with an optimal cutoff value of 6.2. Univariate analysis revealed that factors such as hepatitis B virus DNA level >500 IU/ml, larger maximum tumor dia-meter, and TBS>6.2 were significant risk factors for postoperative tumor recurrence (all P<0.05). Multivariate analysis further indicated that TBS>6.2 ( OR=3.60, 95% CI: 1.081-12.012, P=0.037) and maximum tumor diameter ( OR=1.240, 95% CI: 1.034-1.487, P=0.020) were independent risk factors for postoperative recurrence. Based on these risk factors, a nomogram model was established, achieving a C-index of 0.788. Kaplan-Meier survival analysis showed a better postoperative overall survival and recurrence-free survival of the low TBS group compared to those of the high TBS group (all P<0.05). Conclusion:TBS can serve as a predictive indicator for the recurrence after radical resection in patients with HCC. Both TBS and tumor size are independent risk factors for postoperative recurrence. The nomogram model can be used for predicting recurrence following radical resection in HCC patients.

Objective:To detect the cystic fibrosis transmembrane transduction regulator(CFTR)gene mutations and congenital bilateral absence of vas deferens(CBAVD)susceptibility gene mutations in pa-tients with CBAVD,and to explore their association with the risk of CBAVD.Methods:Whole-exome sequencing and Sanger sequencing validation were conducted on the pathogenic genes CFTR,adhesion G protein-coupled receptor G2(ADGRG2),sodium channel epithelial 1 subunit beta(SCNN1B),carbonic anhydrase 12(CA12),and solute carrier family 9 member A3(SLC9A3)in thirteen cases of isolated CBAVD patients.The polymorphic loci,intron and flanking sequences of CFTR gene were amplified by polymerase chain reaction(PCR)followed by Sanger sequencing.Bioinformatics methods were employed for conservative analysis and deleterious prediction of novel susceptibility gene mutations in CBAVD.Ge-netic analysis was performed on the pedigree of one out of thirteen patients with CBAVD to evaluate the risk of inheritance in offspring.Results:Exome sequencing revealed CFTR gene exon mutations in only six of the thirteen CBAVD patients,with six missense mutations c.2684G＞A(p.Ser895Asn),c.4056G＞C(p.Gln1352His),c.2812G＞(p.Val938Leu),c.3068T＞G(p.Ile1023Arg),c.374T＞C(p.Ile125Thr),c.1666A＞G(p.Ile556Val)),and one nonsense mutation(c.1657C＞T(p.Arg553Ter).Among these six patients,two also had the CFTR homozygous p.V470 site,additional-ly,mutations in CFTR gene exon regions were not detected in the remaining seven patients.Within the thirteen CBAVD patients,three carried the homozygous p.V470 polymorphic site,four carried the 5T al-lele,two carried the TG13 allele,and ten carried the c.-966T＞G site.Four CBAVD patients simulta-neously carried 2-3 of the aforementioned CFTR gene mutation sites.Susceptibility gene mutations in CBAVD among the thirteen patients included one ADGRG2 missense mutation c.2312A＞G(p.Asn771Ser),two SLC9A3 missense mutations c.2395T＞C(p.Cys799Arg),c.493G＞A(p.Val165Ile),one SCNN1B missense mutation c.1514G＞A(p.Arg505His),and one CA12 missense mutation c.1061C＞T(p.Ala354Val).Notably,the SLC9A3 gene c.493 G＞A(p.Val165Ile)mutation site was first identi-fied in CBAVD patients.The five mutations exhibited an extremely low population mutation frequency in the gnomAD database,classifying them as rare mutations.Predictions from Mutation Taster and Poly-phen-2 software indicated that the harmfulness level of the SLC9A3 gene c.493G＞A(p.Val165Ile)site and the SCNN1B gene c.1514G＞A(p.Arg505His)site were disease causing and probably damaging.The genetic analysis of one pedigree revealed that the c.1657C＞T(p.Arg553Ter)mutation in the proband was a de novo mutation,as neither the proband's father nor mother carried this mutation.The proband and his spouse conceived a daughter through assisted reproductive technology,and the daughter inherited the proband's pathogenic mutation c.1657C＞T(p.Arg553Ter).Conclusion:CFTR gene mutations remain the leading cause of CBAVD in Chinese patients;however,the distribution and fre-quency of mutations differ from data reported in other domestic and international studies,highlighting the need to expand the CFTR mutation spectrum in Chinese CBAVD patients.The susceptibility genes ADGRG2,SLC9A3,SCNN1B,and CA12 may explain some cases of CBAVD without CFTR mutations.Given the lack of specific clinical manifestations in CBAVD patients,it is recommended that clinicians conduct further physical examinations and consider scrotal or transrectal ultrasound before making a defi-nitive diagnosis.It is advisable to employ CFTR gene mutation testing in preconception genetic screening to reduce the risk of CBAVD and cystic fibrosis in offspring.

Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.