Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in controlling HBV infection; however, their function is impaired during chronic HBV infection, manifesting as a state of dysfunction. Recent studies have revealed that CD8⁺ T cell dysfunction in chronic HBV infection differs from the classical exhaustion observed in other viral infections or tumors. In 2024, several pivotal studies further elucidated novel mechanisms underlying CD8⁺ T cell dysfunction in chronic HBV infection and identified new therapeutic targets, including 4-1BB and transforming growth factor-beta (TGF-β). This review, while elucidating the dysfunction of CD8⁺ T cells in chronic HBV infection and its underlying mechanisms, focuses on summarizing the key findings from these latest studies and explores their translational value and clinical significance.
Humans ; Hepatitis B, Chronic/virology* ; CD8-Positive T-Lymphocytes/immunology* ; Hepatitis B virus/physiology* ; Animals ; Transforming Growth Factor beta/immunology*

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective To assess the clinical value of prognostic nutritional index(PNI)in predicting the prognosis of patients with advanced liver cancer treated with transarterial chemoembolization(TACE)combined with ablation therapy.Methods A total of 112 patients with advanced liver cancer,who received TACE combined with ablation at the Lishui Municipal Central Hospital of China from January 2020 to January 2024,were enrolled in this study.The general data,survival status,and survival time were collected.The Youden index of PNI was calculated using the receiver operating characteristic(ROC)curve model,and the optimal cutoff value was determined.Based on the optimal cutoff value,the patients were divided into low-PNI group and high-PNI group.The progression-free survival(PFS)and overall survival(OS)time were compared between the two groups,and the independent risk factors affecting PFS and OS were analyzed.Results The Youden index for PNI was 0.43,and the optimal cutoff value of PNI was 43.95.The low-PNI group included 65 patients,and the high-PNI group included 47 patients.There were no statistically significant differences in the baseline data between the two groups.The median PFS and the median OS in the high-PNI group were 13.21 months(95％CI=4.37-22.03)and 40.80 months(95％CI=31.55-50.05)respectively,which were longer than 9.20 months(95％CI=6.58-11.82)and 21.37 months(95％CI=16.56-26.17)respectively in the low-PNI group,the differences were statistically significant(both P＜0.05).The 6-month,one-year and 2-year PFS in the high-PNI group was 56.95％,47.25％and 33.87％respectively,which were higher than 43.95％,32.56％and 16.31％respectively in the low-PNI group.The one-year,2-year and 3-year cumulative survival rates in the high-PNI group were 80.77％,66.66％and 39.40％respectively,which were higher than 63.79％,34.31％and 27.75％respectively in the low-PNI group.Multivariate regression analysis indicated that the number of nodules,metastasis and PNI significantly affected OS,and metastasis and PNI strikingly affected PFS.High PNI was a protective factor for both PFS and OS.Conclusion For patients with advanced liver cancer treated with TACE combined with ablation therapy,PNI is an effective indicator for predicting the prognosis.

Objective To evaluate the combination score of albumin-bilirubin index(ALBI)and alkaline phosphatase(ALP)in predicting the prognosis of patients with cirrhosis complicated by portal hypertension after receiving transjugular intrahepatic portosystemic shunt(TIPS).Methods A total of 61 patients with cirrhosis complicated by portal hypertension,who received TIPS treatment at the Lishui Municipal Central Hospital of China from January 2016 to June 2024,were retrospectively collected.According to the Youden index of ALBI and ALP,the optimal cut-off values were calculated,and the patients were divided into low ALBI-low ALP group(0-point group),high ALBI-high ALP group(2-point group),and high ALBI-low ALP or low ALBI-high ALP group(one-point group).The efficacy of ALBI-ALP score in predicting the prognosis of patients was evaluated,and the survival rate and median survival time were compared between each other among the three groups.The independent risk factors affecting the survival time of patients were analyzed.Results The maximum Youden indexes of ALBI and ALP were 0.31 and 0.34 respectively,and the optimal cut-off values were-1.56 and 108.50 respectively.There were statistically significant differences in MELD score,Child-Pugh classification,and alanine aminotransferase level between each other among the three groups(all P＜0.05).The area under the ROC curve(AUC)of ALBI-ALP score was 0.77(95％ CI:0.66-0.89,P=0.000 2),which was better than 0.52 of the MELD score(95％ CI:0.37-0.67,P=0.77)as well as better than 0.57 of the Child-Pugh classification(95％ CI:0.43-0.72,P=0.34).The total mortality of patients was 49.18％.The mortality in the 0-point group was 11.11％(2/18),which was significantly lower than 59.46％(22/37)in the one-point group as well as than 100％(6/6)in the 2-point group,and the differences were statistically significant(x2=18.20,P＜0.001).In the 0-point group,as a large number of patients were still alive at the end of the study,the median survival time was unable to be calculated.The median survival time in the one-point group was 38.00 months(95％ CI:23.01-52.99 months),which in the 2-point group was only 1.00 month(95％ CI=0.00-2.60 months),the difference was statistically significant(x2=33.08,P＜0.000 1).In the 0-point group,one-point group and 2-point group,the one-year survival rates were 100％,66％ and 17％respectively,the 2-year survival rates were 100％,64％ and 17％ respectively,and the 3-year survival rates were 90％,53％ and 0％ respectively.Cox multivariate regression analysis showed that the combination score of ALBI and ALP(HR=7.11,95％ CI:2.95-17.15)was an independent risk factor for the survival time of patients with cirrhosis complicated by portal hypertension after receiving TIPS.Conclusion The combination score of ALBI and ALP can effectively predict the prognosis of patients with cirrhosis complicated by portal hypertension after receiving TIPS,and this score is an independent risk factor affecting the survival time of patients.

Objective To investigate the relationships of serum procalcitonin(PCT),α1-acid glycoprotein(α1-AGP)and cluster of differentiation 64(CD64)index with the severity of illness and prognosis in patients with pulmonary Candida infection after lung cancer surgery.Methods A pro-spective study was conducted in 120 patients with pulmonary Candida infection after lung cancer sur-gery as infection group,and 60 patients without infection after lung cancer surgery in the same period were selected as control group.Baseline characteristics and laboratory indicators were compared be-tween the two groups.Differences in serum PCT,α1-AGP,CD64 index in peripheral blood,and plasma 1,3-β-D glucan test(BG)were compared among patients with different severities of illness and prognoses in the infection group.The relationship between serum indicators and prognosis as well as their predictive efficiencies were analyzed,and external validation was performed.Results The levels of serum PCT,α1-AGP,CD64 index in peripheral blood,and plasma BG in the infection group were significantly higher than those in the control group(P＜0.05).In the infection group,the levels of serum PCT,α1-AGP,and CD64 gradually decreased significantly in patients with severe,moderate,and mild illness,and the levels of these indicators in dead patients were significantly higher than those in surviving patients(P＜0.05).Survival curve analysis showed that patients with low levels of serum PCT,α1-AGP,and CD64 index before treatment had higher survival rates than those with high levels of these indicators.Receiver operating characteristic(ROC)curve analysis revealed that the combined prediction of PCT,α1-AGP,and CD64 index for mortality was superior to individual indicators or their pairwise combinations,and external validation confirmed the good predictive efficacy of the combined prediction.Conclusion PCT,α1-AGP,and CD64 index are closely related to pulmonary Candida infection after lung cancer surgery,and the combined detection of these indicators has certain predictive value for 28-day prognosis.

Objective A feasible and stable mouse model of thoracic aortic dissection(TAD)combined with acute lung injury(ALI)was established using β-aminopropionitrile monofumarate(BAPN)1 g/(kg·d)administered in drinking water.The mouse model of TAD combined with acute lung injury(ALI)was established to provide a rational animal model to study TAD combined with ALI.Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly allocated to a CON group(normal dietary water;15 mice)or BAPN group(administration in sterile water at 1 g/(kg·d);30 mice)for 4 weeks.During the experimental period,the general condition and modeling rate of mice were observed.TAD model mice were validated,and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues.HE pathological staining,the wet/dry weight(W/D)ratio,total protein level in bronchioalveolar lavage fluid(BALF),and interleukin(IL)-1 β,IL-6,and tumor necrosis factor-α(TNF-α)in BALF)were used to validate the TAD combined ALI model in mice.Results BAPN treatment significantly delayed the increase in body mass and water intake of mice.Compared with CON and non-TAD groups,the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened(P＜0.05).HE staining of the aorta showed significant thickening of the middle aortic layer,and the structure of the aortic wall was damaged and disordered.HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen,alveolar wall epithelial exfoliation and hyaline membrane formation,and a significant increase in the pathological scores of lung injury(P＜0.05).Total protein levels and expression of IL-1β,IL-6,and TNF-α in lung tissue,W/D ratio,and BALF were also significantly increased(P＜0.05),whereas no significant difference was observed in the above indexes between the other two groups.Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective To discuss the effect of PI3K-AKT signaling pathway regulated by microRNA-155(miRNA-155)targeted protein tyrosine phosphatase non-receptor type 21(PTPN21)on the proliferation,migration and invasion of hepatocellular carcinoma(HCC)cells.Methods Lentivirus transfection was used to silence the expression of miRNA-155 in human Huh7 HCC cells,and real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)was used to detect the silencing effect of miR-155.After obtaining stable cell lines,the cell lines were randomly divided into Blank group(normal Huh7 cells),shNC group(Huh7 cells+empty miR-155 vector),sh-miR-155(Huh7 cells+miR-155 silencing),sh-miR-155+Recilisib group(Huh7 cells+miR-155 silencing+PI3K-AKT agonist),shNC+Recilisib group(Huh7 cells+empty miR-155 vector+PI3K-AKT agonist).Dual luciferase assay was used to determine whether PTPN21 was the downstream of miR-155.The cell proliferation ability of cells in each group was detected by MTT assay.The apoptosis level of each group was tested by flow cytometry.The invasion and migration ability of cells was assessed by Transwell assay.Western blot analysis was used to observe the differences in protein expression of PTPN21,PI3K,P-PI3K,AKT,P-AKT,and apoptosis-related proteins including BAX,BCL-2 and caspase-3 in all groups.Results The expression level of miR-155 in sh-miR-155 group was lower than that in Blank group and shNC group(P＜0.000 1),and the difference in miR-155 expression level between Blank group and shNC group was not statistically significant(P＞0.05).MTT results showed that A values of Huh7 cells at 2,3,4 and 5 day in sh-miR-155 group were lower than those in Blank group and shNC group(P＜0.000 1),while these differences between Blank group and shNC group were not statistically significant(P＞0.05).In sh-miR-155 group the A values at 2,3,4 and 5 day were lower than those in sh-miR-155+Recilisib group and shNC+Recilisib group(P=0.0052 and P＜0.0001,respectively),while the A values at 2,3,4 and 5 day in sh-miR-155+Recilisib were lower than those in shNC+Recilisib group(P＜0.000 1).There was no significant differences in cell migration and number of invasion cells between the Blank group and shNC group(P＞0.05).After activation of PI3K-AKT signaling pathway,the migration and invasion capacity of HCC cells in the shNC+Recilisib group were significantly enhanced when compared with the Blank group(P＜0.000 1).In contrast,the number of migrated and invaded Huh7 cells after miR-155 silencing was significantly lower than that in the Blank group and shNC group(P＜0.000 1)and this phenomenon became reversed by PI3K agonist.Compared with the sh-miR-155 group,in the sh-miR-155+Recilisib group the migration and invasion ability of HCC cells was enhanced(P=0.000 2).Lentiviral transfection of Huh7 human HCC cells to silence miR-155 and downregulate miR-155 inhibiting PTPN21 regulation of the PI3K-AKT signaling pathway,thus inhibiting the invasion,migration and proliferation ability of HCC cells and promoting the apoptosis of HCC cells.Conclusion miR-155 inhibits the migration,invasion and proliferation of HCC cells through targeting PTPN21 regulation of PI3K-AKT signaling pathway.The miR-155 may be a potential therapeutic target for HCC in the future.(J Intervent Radiol,2024,32:44-51)

Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.

Objective:To observe the therapeutic effect of vibrating the abdomen on anorexia model rats,as well as its effects on cholecystokinin octapeptide(CCK-8)and motilin(MTL)in the peripheral blood. Methods:Forty young rats were randomly divided into a normal group(n=10)and a modeling group(n=30).Rats in the normal group were fed common feed.The anorexia model was established by the etiological simulation method in the modeling group,and these rats were further randomly divided into a drug group,a vibrating abdomen group,and a model group 3 weeks after the anorexia model was induced,with 10 rats in each group.The drug group was given Jian Wei Xiao Shi Pian by intragastric administration at a dose of 0.72 g/(kg·bw)(0.72 g drug was dissolved in 10 mL purified water).The normal group and the model group were given purified water once a day in the morning.The vibrating abdomen group was treated with vibrating the abdomen once a day for 21 times.The body mass,food intake,serum CCK-8,MTL,gastrin(GAS),neurotensin(NT)levels,and the intestinal propulsion rate of rats in each group were measured. Results:Compared with the model group,the body mass,food intake,serum MTL and GAS levels,and the small intestine propulsion rate increased significantly,and the serum CCK-8 and NT levels,the gastric residual rate decreased significantly in the vibrating abdomen group and the drug group(P<0.05).There were no significant differences between the vibrating abdomen group and the drug group(P>0.05). Conclusion:Vibrating the abdomen increases the food intake and body mass of anorexia model rats,reduces the residue of gastric contents,improves the small intestine propulsion rate,and therefore has a good therapeutic effect on anorexia.The mechanism may be related to inhibiting the secretion of CCK-8 and NT in plasma and promoting the release of MTL and GAS in serum.