[Abstract] Objective To analysis the differentially expressed proteins and their biological functions in diseased rectal tissues of patients with obstructed defecation syndrome(ODS). Methods 20 patients with ODS and 10 patients with prolapse of mixed hemorrhoids(without constipation symptoms) were included.All patients underwent stapled transanal rectal resection(STARR) and then rectal specimens were collected.Isobaric tags for relative and absolute quantification(iTRAQ) was used to screen the differentially expressed protein profiles between patients with ODS and with mixed hemorrhoid prolapse,and all differentially expressed proteins were analyzed by Gene Ontology(GO)analysis,Kyoto Encyclopedia of genes and genomes(KEGG) analysis and signal peptide(signalP) analysis. Results A total of 164 proteins(88 up-regulated and 76 down-regulated) were differentially expressed between ODS patients and control part with mixed hemorrhoid prolapse.The biological processes involved mainly include cellular processes,biological regulation and metabolic processes.The cell components involved mainly include biochemical processes and cell structure.The molecular functions involved mainly include binding sites,catalytic activity and Molecular function regulation,etc.The signaling pathways involved mainly include neurodegenerative diseases,endocrine and metabolic diseases and immune diseases. Conclusion There are differences in rectal tissue proteins between ODS patients and non-constipation patients.The biological processes and signal pathways involved in the differentially expressed proteins may be connected with the pathogenesis of ODS.

[Abstract] Objective To investigate the efficacy and safety of advanced Siewert type Ⅱ/Ⅲ AEG neoadjuvant chemotherapy for retroperitoneal laparoscopic surgery and open surgery.Methods From January 2015 to December 2019,46 patients with locally advanced Siewert Ⅱ/Ⅲ AEG in Xishui People’s Hospital received neoadjuvant chemotherapy,and they were randomly divided into laparoscopic total gastrectomy(LATG)+D2 lymphadenectomy(LATG group,23 cases) or open total gastrectomy(OTG)+D2 lymphadenectomy(OTG group,23 cases).Results Both groups of patients completed preoperative neoadjuvant chemotherapy,and there was no interruption of treatment.Both groups achieved R0 resection and successfully completed the operation.There were significant differences in operation time[(251.53±32.35)min VS (233.68±24.13)min],intraoperative blood loss[(146.00±47.68)ml VS (181.21±42.54)ml],postoperative exhaust time[(2.89±0.56)d vs (3.24±0.34)d] and postoperative hospital stay[(12.65±2.17)d vs (14.59±3.58)d] between LATG group and OTG group(P<0.05).There was no significant difference in the number of lymph node dissection(32.19±3.23 VS 30.84±2.85)(P>0.05).In terms of postoperative complications,there was significant difference in wound infection(1 case,VS,4 cases)(P<0.05),but there was no significant difference in anastomotic stenosis(2 cases,vs,2 cases)(P>0.05).There were no serious complications such as anastomotic leakage,anastomotic bleeding and perioperative death in both groups.Conclusion After neoadjuvant chemotherapy for locally advanced Siewert Ⅱ/Ⅲ AEG patients,LATG group is equivalent to OTG group in radical tumor resection,lymph node dissection,postoperative bleeding and anastomotic leakage,but it has obvious advantages in intraoperative bleeding,postoperative intestinal function recovery,wound infection and postoperative hospital stay.

[Abstract] Objective To explore the effect of rapid rehabilitation surgery on the nutritional status of patients undergoing laparoscopic-assisted pyloric sparing gastrectomy for early gastric cancer. Methods A retrospective selection of 80 patients with early gastric cancer who were diagnosed in our hospital from March 2014 to August 2018 and combined with early gastric cancer laparoscopic-assisted pyloric sparing gastrectomy were used as research data.According to whether or not rapid rehabilitation surgery was performed,they were divided into control group(48 cases) and observation group(32 cases),among them,the traditional surgical diagnosis and treatment plan for the control group,the rapid rehabilitation surgical treatment plan for the observation group,and observe and record the postoperative recovery of the two groups of patients(hospitalization time,first exhaust time,gastric tube removal time,and liquid diet recovery time And defecation time),postoperative nutritional status(ALB,PAB,HB level),and follow-up status(quality of life,complication rate,and survival rate). Results Postoperative hospitalization time,first exhaust time,gastric tube removal time,restoring liquid diet time,and defecation time in the observation group were shorter than those in the control group,and the difference was statistically significant(P＜0.05).There was no significant difference in the scorespreoperative PG-SGA in the two groups (P>0.05).The PG-SGA scores of the two groups of patients decreased after 14 days,but the PG-SGA scores of patients in the observation group decreased more significantly,and the difference was statistically significant(P＜0.05).After 30 days,the PG-SGA score of the observation group was significantly lower than that of the control group,and the difference was statistically significant(P＜0.05).There was no significant difference in the levels of ALB,PAB,and HB between the two groups before surgery(P>0.05).The level of ALB,PAB,and HB were significantly reduced in the two groups at 7 days after surgery,but the level of PAB decreased more significantly in the control group,and the difference was statistically significant(P＜0.05).The level of ALB,PAB,and HB in the two groups were significantly lower on day 14 after surgery than on day 7 after surgery.The levels of ALB,PAB,and HB in the observation group were significantly higher than those in the control group,and the difference was statistically significant(P＜0.05);The postoperative follow-up found that the incidence of complications of grade Ⅰ,grade Ⅱ,grade Ⅲ,grade Ⅳ,and grade Ⅴ in the observation group were 15.63%,40.63%,6.25%,3.13%,and 3.13%,respectively,which were significantly lower than those in the control group(16.67%,50.00%,8.33%,6.25%,4.17%,respectively),the difference was statistically significant(P＜0.05). Conclusion Rapid rehabilitation surgery can speed up the recovery of patients after surgery,reduce the length of hospitalization,and restore the nutritional level of patients faster after surgery,which is conducive to the prognosis of the disease and reduces complications.

[Abstract] Objective To investigate the effect of accelerated rehabilitation surgery (ERAS) in neuroendoscopic transsphenoidal approach for pituitary adenoma resection.From February 2020 to September 2020,the data of 60 cases of pituitary adenoma were retrospectively analyzed.30 cases underwent surgery according to routine preparation and routine operation as control group.ERAS group was 30 patients who received ERAS concept during perioperative period.The average length of postoperative hospital stay,incidence of postoperative symptoms and complications,VAS score of nasal distension after surgery,and investigation rate of patient satisfaction during hospitalization were compared between the two groups.Results The mean postoperative hospital stay in ERAS group[(46±2.2)h] was significantly better than that in control group[(135±10.4)h](P<0.05).The incidence of clinical symptoms and complications,such as dyspnea,headache,nasal distension and nasal bleeding,was higher in ERAS group than in control group(P<0.05).The incidence of unplanned secondary surgery due to nasal bleeding was significantly higher in ERAS group (0) than in control group (13%) (P<0.05).VAS score of nasal swelling pain in ERAS group (1.12±0.45) was significantly higher than that in control group (6.61±0.92) (P<0.05).Patients’ satisfaction during hospitalization in ERAS group [(97.63±2.37)%] was better than that in control group [(80.20±3.42)%] (P<0.05).Conclusion The application of ERAS concept in neuroendoscopic transsphenoidal approach for pituitary adenoma resection can reduce postoperative systemic or local complications and shorten the average postoperative hospital stay,improved the surgical efficacy and satisfaction of patients.

[Abstract] ObjectiveTo explore the learning curve assessment for percutaneous trans-jugular vein closure of atrial septal defect with curve-controllable sheath catheter.MethodsThe present analysis included 40 atrial septal defect patients who were consecutively undergone percutaneous trans-jugular vein closure with curve-controllable sheath catheter from a single-center between January 2015 and June 2018.The procedure time,puncture time，intracardiac operation time and intraoperative blood loss were recorded．The learning curve of percutaneous trans-jugular vein closure of atrial septal defect with curve-controllable sheath catheter was analyzed with cumulative summation(CUSUM)．Results40 cases were underwent interventional therapy successfully.The average time of procedure,puncture time，intracardiac operation were(31.2±8.7)min,(17.1±4.4)min and (14.1±5.3)min,respectively;and the average amount of intraoperative blood loss was(7.6±1.8)ml.The fitting equation was Σi(CUSUM)= 0.001X3-0.123X2+3.264X-2.420,and the R² value was 0.99.The curve slope turned into negative at the 18th case.18 was the minimum number of surgeries that need to be accumulated to cross the learning curve.Conclusion With the increasing of operator’s experience,the safety of percutaneous trans-jugular vein closure of atrial septal defect with curve-controllable sheath catheter was increased.It is suggested from our data that the surgeons need finish about 18 cages to skill this surgery method．

[Abstract] Objective To compare effects of ticagrelor/clopidogrel on bypass in patients with hypertension complicated with diabetes 1 year after CABG.Methods 78 patients undergoing CABG in our hospital from March 2016 to August 2020 were selected and divided into group A(clopidogrel) and group B(ticagrelor).CTA was performed 1 year after the operation to assess bypass,and adverse events were followed up.Results There were no significant differences in general data,total/arterial bridge vessel patency,angina and bleeding events between 2 groups(P>0.05).The patency of vein bypass in group B was significantly higher than group A(76.8%vs.89.2%,P=0.042).Logistic regression suggested that ticagrelor reduced the risk of bridging stenosis(OR=2.488,95%CI:1.016-6.091,P=0.046).〖WTHZ〗Conclusion 1 year after CABG,ticagrelor better maintained bridge patency in hypertensive patients with type 2 diabetes.

[Abstract] Objective To evaluate the effect of VPI on the survival of patients with postoperative stage ⅢA/N2M0 non-small cell lung cancer.Methods Using the Surveillance,Epidemiology,and Final Results(SEER) database,we screened patients with stage ⅢA/N2M0 non-small cell lung cancer who underwent surgery between 2010 and 2015.Cox proportional hazards regression is used to determine factors related to survival.Kaplan-Meier was used to analyze cancer-specific survival(CSS) and overall survival(OS) between the non-VPI group and the VPI group.Results Prognostic factors related to the VPI included race(P<0.001) and adenocarcinoma(P<0.001).VPI was an important independent prognostic factor of OS(HR,1.432;95% CI,1.082-1.573,P=0.006). Conclusion Our results show that VPI is a poor prognostic factor in patients with postoperative stage ⅢA/N2 non-small cell lung cancer.Studies have shown that chemotherapy significantly improves the overall survival rate of patients with stage ⅢA/N2M 0 non-small cell lung cancer after surgery,and reduces the related mortality of lung cancer,especially for non-VPI patients.

[Abstract] Objective To explore the expression levels of FOXQ1 and CyclinD1 in non-small cell lung cancer (NSCLC),and analyze their relationship with clinicopathological features and prognosis. Methods 196 cancer tissue samples and 30 adjacent tissue samples of NSCLC patients treated in our hospital from December 2014 to October 2017 were selected.The expressions of FOXQ1 and cyclinD1 protein in NSCLC tissues and adjacent tissues were detected by EnVisio immunohistochemistry.The expression levels of FOXQ1 and CyclinD1 in NSCLC and their relationship with clinicopathological parameters were analyzed.Spearman correlation was used to analyze the correlation between FOXQ1 and CyclinD1.Cox proportional hazards regression model was used to analyze the prognostic factors of NSCLC patients.Kaplan Meier survival curve was used to analyze the relationship between the expression of FOXQ1 and CyclinD and the prognosis. Results The high expression rates of FOXQ1 and cyclinD1 protein in NSCLC tissues were higher than those in paracancerous tissues (P<0.05).The high expression of FOXQ1 and CyclinDl in NSCLC was correlated with pathological differentiation,clinical stage and lymph node metastasis (P<0.05).Spearman correlation analysis showed that there was a positive correlation between foxq1 expression and CyclinD1 expression in NSCLC (P<0.05).Cox regression analysis showed that high expression of FOXQ1,CyclinD1 and FOXQ1+CyclinD1 were independent risk factors for progression free survival (PFS) and overall survival (OS) of NSCLC patients (P<0.05).Kaplan Meier analysis showed that the cumulative survival rates of PFS and OS in patients with high expression of FOXQ1 and CyclinDl were lower than those in other patients (P<0.05).The cumulative survival rates of PFS and OS in patients with high expression of FOXQ1 and CyclinDl were lower than those in patients with high expression of FOXQ1 and CyclinD1 alone (P<0.05).Conclusion FOXQ1 and CyclinD1 are highly expressed in NSCLC tissues,which are closely related to the occurrence,development and prognosis of the disease.FOXQ1 and cyclinD1 protein are positively correlated,the combined detection of both can better judge the prognosis of NSCLC patients.

[Abstract] Objective To investigate the value of modified Glasgow prognostic score(mGPS)  combined with Fibrinogen to pre-albumin ratio(FPR) in the prognostic evaluation of thoracoscopic lobectomy for lung cancer.Methods The clinical and follow-up data of 63 patients with lung cancer who underwent thoracoscopic lobectomy in Huanggang Central Hospital from October 2016 to December 2019 were retrospectively analyzed.FPR of patients before surgery was detected and calculated,and the mGPS was recorded.The receiver operating characteristic curve(ROC) was used to determine the optimal cut-off value of FPR,and χ² test was used to analyze the relationship between mGPS,FPR and the clinicopathological characteristics of lung cancer,and single factor and multivariate Cox proportional hazard regression models were used to analyze the influence factors related to the prognosis of patients with lung cancer underwent thoracoscopic lobectomy.Results According to the mGPS,0 points were included in the normal group(38 cases),and 1~2 points were included in the abnormal group(25 cases).The best cutoff value of FPR by ROC curve was 0.096,and the patients were divided into the high FPR group(FPR>0.096,n=19) and low FPR group(FPR≤0.096,n=44).The proportion of TNM III stage in lung cancer patients with abnormal mGPS and high FPR was higher(P<0.05).The 3 year disease-free survival rate of the normal mGPS group and the low FPR group was higher than that of the abnormal mGPS group and the high FPR group(78.95% vs 48.00%,75.00% vs 47.37%)(P<0.05).The 3 year disease-free survival rate of 18 patients with abnormal mGPS combined with FPR(abnormal mGPS and high FPR) was 38.89%,which was significantly lower than that of the two non-uniform abnormal lung cancer patients(77.78%,P<0.05).TNM stage Ⅲ,abnormal mGPS,high FPR,and abnormal mGPS combined with FPR(abnormal mGPS and high FPR) were all independent risk factors of the prognosis of lung cancer patients after thoracoscopic lobectomy(P<0.05).Conclusion he survival rate of lung cancer patients undergoing thoracoscopic lobectomy with abnormal preoperative mGPS or high FPR is significantly reduced,and the survival rate of patients with both abnormalities is lower.The combination of mGPS and FPR is expected to be an effective indicator for evaluating the prognosis of lung cancer patients.

[Abstract] Objective To explore the protein expression profile and key protein for plasma cell mastitis by proteomics techniques.Methods We collected the plasma cell mastitis tissues and adjacent normal tissues following surgical removal of affected tissues from 4 plasma cell mastitis patients.Then,we extracted the proteins,analyzed the differentially expressed proteins in plasma cell mastitis by applying isobaric tags for relative and absolute quantitation (iTRAQ) technology,and conducted functional enrichment analysis using these differentially expressed proteins.Results In our study,915 differentially expressed proteins were identified including 795 upregulated proteins and 120 downregulated proteins in plasma cell mastitis tissues.Functional enrichment analysis showed these differentially expressed proteins were mainly involved in cell adhesion,and inflammatory response.KEGG pathway analysis showed these differentially expressed proteins were mainly enriched in immune system associated pathway.Conclusion Differentially expressed proteins in plasma cell mastitis are involved in related signaling pathways and may be key molecules in the development of plasma cell mastitis.

[Abstract] Objective To investigate the clinical skills of difficult laparoscopic cholecystectomy(LC) and improve the safety of LC in the treatment of difficult gallbladder stone disease. Methods The clinical data of 127 cases of difficult LC in the Department of Hepatobiliary Surgery,Xiaogan Hospital affiliated to Wuhan University of Science and Technology from March 2018 to March 2021 were retrospectively analyzed.109 patients were completed LC successfully by rouviere sulcus guided dissociation method,among which 6 patients with vascular or cystic duct inflow variation used anterior-inverse combination method.13 patients with “frozen structure” in gallbladder triangle underwent laparoscopic subtotal cholecystectomy;5 patients were converted to open surgery.Results The mean operation time was (85.2±18.7)min,and the mean blood loss was (73.3±15.7)ml.There were no bile duct or portal vein injuries and 6 cases of biliary leakage were cured after 9 to 15 days of adequate drainage.The follow-up period ranged from 6 to 12 months,and there were no Long-term surgical complications.Conclusion Under the condition of abundant LC technology, LC is safe and feasible to treat complex gallstones.

[Abstract] Objective To investigate the effects of TP53 regulation of apoptosis inhibitor 1(TRIAP1) on the proliferation and invasion ability of hepatoma cells Huh7 and HepG2.Methods In this study,the difference of TRIAP1 expression in tumor tissues and normal tissues was analyzed using TCGA database,and the correlation between TRIAP1 and prognosis of HCC patients was analyzed.TRIAP1 knockdown cell lines were constructed by transfection with siRNA and control group.Western blot was used to verify knockdown efficiency of TRIAP1 siRNA transfection and the levels of other related proteins.The effect of TRIAP1 on the apoptosis of HCC cells was detected by Capase 3/7 active cell apoptosis kit and Annex INV /PI assay,and the effect of TRIAP1 on the proliferation of HCC cells was detected by CCK8.Results TCGA database analysis showed that TRIAP1 expression was up-regulated in HCC cells,and was negatively correlated with prognosis of HCC patients.siTRIAP1 was transfected into Huh7 and HepG2 to downregulate TRIAP1 expression..The mRNA and protein expression levels of p21 in the TRIAP1 knockdown group were significantly up-regulated,and the proliferation ability of the TRIAP1 knockdown group was decreased,while the number of apoptotic cells was increased.Conclusion The expression of TRIAP1 is up-regulated in HCC cells,and the expression of cell cycle related p21 expression is decreased and then regulate the tumor cell cycle.Inhibition of TRIAP1 can significantly up-regulate p21,inhibit the proliferation ability of HCC cells,and promote the apoptosis process.

[Abstract] Objective To explore one-year change trajectory in body mass index after sleeve gastrectomy among severe obesity patients,and then identify predictive factors of different trajectories.Methods 241 patients with sleeve gastrectomy were included.The data of body mass index at baseline,1,3,6,12 months after sleeve gastrectomy were used to construct the growth mixed model.And the baseline data were compared according to various trajectories.Results Three different trajectories were finally obtained,named as “Routine weight loss trajectory”(29.5%),“Rapid weight loss trajectory” (27.0%) and “Slow weight loss trajectory” (43.6%),respectively.There were significant differences in age,gender and marital status between different trajectories.Further paired compariso n showed that gender and marital status had significant effect on the difference between trajectories.Conclusion BMI decreased slowly in 43.6% patients after sleeve gastrectomy.Female and married status were important predictors of the unsatisfactory one-year weight loss trajectory after sleeve gastrectomy.Younger age also helps predict postoperative weight loss.

[Abstract] Objective To analyze and evaluate the feasibility and effectiveness of AngioJet thrombus aspiration device combined with balloon dilation for the immediate efficacy and short-term follow-up of 13 patients with acute dialysis access obstruction treated by AngioJet thrombus aspiration device in our hospital. Methods The clinical data of 13 patients with acute dialysis access obstruction treated by AngioJet thrombus aspiration device combined with balloon dilation in our department from 2019 to 2020 were retrospectively analyzed.The preoperative and postoperative arteriovenous fistula tremor,the degree of arteriovenous fistula thrombus obstruction under ultrasound and the blood flow grade before and after thrombolysis in myocardial infarction(TIMI) were analyzed.To evaluate the degree of thrombus clearance and blood perfusion of arteriovenous fistula and evaluate the clinical efficacy. Results 13 patients with acute dialysis access obstruction were treated with AngioJet thrombus aspiration device combined with balloon dilation successfully,the surgical success rate was 100%.Preoperative TIMI grade 0 in 13 cases.Immediately after operation,13 cases were graded 2,and 0 cases were graded 3.During the operation,13 cases of residual stenosis >50% were treated with high pressure balloon dilatation and angioplasty.After angiography,13 cases received TIMI grade 3.The 13 patients recovered tremor immediately after treatment,and color ultrasound 24 hours after surgery indicated that the diameter of the arteriovenous fistula drainage vein was ≥5mm,and the blood flow was >500ml/min.No serious complications such as digestive tract and intracranial hemorrhage were observed in the 13 patients.After 6 months of outpatient follow-up,13 patients were discharged:the arteriovenous fistula tremor was good;D-dimer <0.55ng/L;TIMI grade 2 in 3 cases and grade 3 in 10 cases;Ultrasonography showed that the blood flow in the arteriovenous internal fistula was patency in 13 patients,and the blood flow was >500ml/min.Able to meet dialysis requirements. Conclusion AngioJet thrombus aspiration device combined with balloon dilation in the treatment of patients with acute obstruction of dialysis access has the following characteristics:less surgical trauma,fewer complications,high fistula preservation rate,simple operation and definite curative effect.

[Abstract] Objective To detect the superiority of laparoscopic operation over laparotomy in the treatment of multiple magnetic foreign body ingestion in children.Methods A total of 38 children with multiple magnetic foreign bodies ingestion from February 2011 to July 2021 were retrospectively analyzed and divided into two groups,laparoscopic group (18 cases) and laparotomy group (20 cases).The information including age,gender,and number of magnetic beads,number of perforations and location of intestinal perforations were counted;additional information containing the operative time,blood loss,postoperative pain score,time to move freely,fasting time,complications and hospital stay was analyzed. Results In the laparoscopic group,the operative time was (125.6±34.0)minutes,the intraoperative blood loss was (5.9±1.9)ml,and there were 0 cases of postoperative complications.The data of the laparotomy group were （128.0±33.0）minutes,（6.9±2.7）ml、2 cases,there was no significant difference between the two groups (P>0.05).The postoperative pain score in the laparoscopy group was (3.2±0.5)points,the time to move freely was (57.4±14.7)hours,and the fasting time (3.8±0.5)days,hospital stay (6.5±0.7)days,the laparotomy group were (4.4±0.5)points,(83.9±18.9)hours,(5.7±1.9)days,(8.9±2.2)days,there was significant difference between the two groups (P<0.05).
Conclusion Laparoscopic surgery has certain advantages of enhancing recovery and releasing pain over laparotomy operation in the treatment of multiple magnetic foreign body ingestion in children.

[Abstract] Objective To explore the expression of crystallinalpha B(CRYAB) in elderly lung squamous cell carcinoma(LUSC) and investigate the relationship between its expression and clinical characteristics of LUSC.Methods Twenty cases of cancer tissues and adjacent tissues of LUSC patients from January 2014 to December 2016 were selected for qPCR detection and immunohistochemistry analysis(IHC) in tissue microarrays(59 LUCC samples and corresponding non-cancerous samples) were performed to characterize CRYAB expression in LUSC.Cox regression and KaplanMeier survival analyses were carried out to evaluate the prognostic indicator of LUSC.Results qPCR test showed that the expression value of CRYAB mRNA in LUSC was (4.456±1.512),which was significantly higher than that in adjacent tissue (2.944±0.4907),and the difference was statistically significant(P<0.05).Immunohistochemical detection showed that the protein expression of CRYAB in LUSC was significantly higher than that in the adjacent control group(P<0.05).Moreover,the expression level of CRYAB protein in LUSC was significantly correlated to T status(P<0.05).Univatiate and multivariate analysis of Cox regression showed that CRYAB expression could be identified as an independent prognosis factors for LUSC(P<0.05).High expression of CRYAB suggests poor prognosis.ConclusionCRYAB is highly expressed in LUSC patients.The data suggest that CRYAB expression is associated with malignant phenotypes of LUSCC and it may serve as a novel prognostic factor for LUSC．

［Abstract］Hepatocellular Carcinoma(HCC) is one of the most common malignant tumors,which ranks second in the mortality rate of malignant tumors in China.At diagnosis,most patients were in advanced stages already.They have lost surgical opportunities,and also achieved poor response from radiation therapy,chemotherapy,and traditional immunotherapy.In recent years,major advances have been made in anti-PD treatment for HCC,bringing new hope to advanced cancer patients.The anti-PD therapy for HCC has undergone the 1.0 era of anti-PD-1/PD-L1 monoclonal antibody monotherapy,the 2.0 era of combined molecular targeted drug application,and the 3.0 era of clinical application research stage of further combined locoregional therapy.With the development of the PD-1/PD-L1 inhibitors-based immunotherapy,the therapeutic effect of HCC has been further improved.The latest clinical research explores adoptive tumor-infiltrating lymphocytes therapy on the basis of immunotherapy 3.0,and the preliminary research has obtained good clinical efficacy,which also marks the advent of the era of HCC immunotherapy 4.0.