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 evaluate the quality of Mongolian medicine Sendeng-4 based on qualitative and quantitative analysis combined with chemical pattern recognition， in order to provide the reference for its quality control. METHODS The chemical components in Sendeng-4 were analyzed qualitatively by HPLC-Q-Exactive-MS. The contents of 16 components （methyl gallate， ethyl gallate， epicatechin， dihydromyricetin， genipin-1-O-β-D-gentiobioside， caffeic acid， catechin， corilagin， deacetylasperulosidic acid methyl ester， rutin， geniposide， luteolin， myricetin， quercetin， ferulic acid， and toosendanin） in 15 batches of Sendeng-4 （sample S1-S15） were quantitatively analyzed by HPLC-MS/MS. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares discriminant analysis were conducted and variable importance projection （VIP） value greater than 1 was used as the index to screen the differential components. RESULTS A total of 73 chemical components were identified in Sendeng-4， including 20 flavonoids， 16 tannins， 14 organic acids， etc. According to the quantitative analysis， the results exhibited that the average contentsthe of above 16 components in 15 batches of Sendeng-4 were 3.683-7.730， 2.391-6.952， 2 275.538-4 377.491， 2 699.188-3 537.924， 858.266-1 377.393， 3.366-11.003， 140.624-315.683，414.629-978.334， 285.501-1 510.457， 27.799-48.325， 3 625.415-6 309.563， 0.506-0.656， 442.337-649.283， 47.093-59.736， 12.942-15.822， 127.738-326.649 μg/g， respectively. According to the results of CA and PCA， 15 batches of samples could be clustered into two categories: S1-S3， S5-S6， S9-S10 and S13 were clustered into one category； S4， S7-S8， S11-S12， S14-S15 were clustered into one category. VIP values of geniposide， epicatechin， deacetylasperulosidic acid methyl ester and genipin-1-O- β-D-gentiobioside were all greater than 1. CONCLUSIONS HPLC-Q-Exactive-MS and HPLC-MS/MS techniques are employed for the qualitative and quantitative analysis of Sendeng-4. Through chemical pattern recognition analysis， four differential components are identified: geniposide， epicatechin， deacetylasperulosidic acid methyl ester， and genipin-1-O-β-D-gentiobioside.

Objective:To explore the influencing factors for pathological upgrading in prostate cancer patients with a Gleason score of 3 + 3 undergoing targeted biopsy，and to establish a nomogram prediction model.Methods:A retrospective analysis was conducted on 191 patients with localized prostate cancer diagnosed with a Gleason score of 3 + 3 through targeted biopsies at the First Affiliated Hospital of Nanjing Medical University from January 2020 to June 2024. The age of the patients was 67（61，73）years，with prostate-specific antigen（PSA）level of 7.44（5.53，10.19）ng/ml，prostate volume of 35.64（26.59，48.97）ml，and PSA density（PSAD）of 0.20（0.14，0.31）ng/ml 2. Among them，61 cases（31.94%）had a Prostate Imaging Reporting and Data System（PI-RADS）score of 3，104 cases（54.45%）had a score of 4，and 26 cases（13.61%）had a score of 5. The diameter of the main lesion was 10.75（7.86，14.00）mm. The lesions were located in the peripheral zone in 78 cases（40.84%），the transition zone in 99 cases（51.83%），and the anterior fibromuscular stroma in 14 cases（7.33%）. The lesions were found at the apex in 56 cases（29.32%），in the body in 120 cases（62.83%），and at the base in 15 cases（7.85%）. MRI revealed only one lesion with a PI-RADS score ≥ 3 in 131 cases，two suspected lesions in 43 cases，three suspected lesions in 12 cases，and four suspected lesions in 5 cases. Systematic biopsy was positive in 121 cases（63.4%）and negative in 70 cases（36.6%）. The lesions were confined to the left lobe in 63 cases（32.98%），right lobe in 68 cases（35.60%），and involved both lobes in 60 cases（31.41%）. The interval between biopsy and surgery was 9.0（7.0，14.0）days. Univariate analyses were performed using Mann-Whitney U tests or χ2 tests，and multivariate logistic regression was used to identify independent predictors of pathological upgrading. A nomogram model was constructed based on these independent predictors. The model’s discriminative ability was assessed using the area under the receiver operating characteristic（ROC）curve（AUC），and internal validation of the model’s consistency was conducted using the bootstrap resampling method. Decision curve analysis（DCA）was performed to assess clinical utility. Results:Among the 191 cases，60（31.4%）had no pathological upgrading after surgery，while 131（68.6%）showed upgrading. Univariate analysis showed that the maximum diameter of the main lesion［9.0（6.0，13.2）mm vs. 11.0（8.4，14.0）mm］，number of suspicious lesions on MRI［1.0（1.0，1.0）vs. 1.0（1.0，2.0）］，number of positive systematic biopsy cores［1.0（0，2.0）vs. 1.0（0，3.0）］，percentage of positive systematic biopsy cores［0.08（0，0.17）vs. 0.12（0，0.25）］，number of positive targeted biopsy cores［2.0（1.0，3.0）vs. 3.0（1.0，4.0）］，percentage of positive targeted biopsy cores［0.37（0.24，0.75）vs. 0.50（0.38，0.85）］，level of the index lesion，location of the index lesion，and PI-RADS score were associated with pathological upgrading（ P < 0.05）. Multivariate logistic regression analysis showed that PI-RADS score 4（ OR = 5.88，95% CI 2.41 - 14.35），number of suspicious lesions on MRI（ OR = 4.15，95% CI 1.88 - 9.17），location of the index lesion in the transition zone（ OR = 6.86，95% CI 2.81 - 16.73），and percentage of positive targeted biopsy cores（ OR = 4.37，95% CI 1.38 - 14.90）were independent risk factors for pathological upgrading（ P < 0.05）. The nomogram model constructed using these predictors had an AUC of 0.845. Internal validation using the Bootstrap method yielded an AUC value of 0.812，indicating high predictive accuracy of the model. The calibration curve indicated good calibration. Decision curve analysis showed that the threshold range for net benefit in the model was between 12% - 100%. Conclusions:The PI-RADS score 4，the number of lesions with PI-RADS ≥ 3，the location of the main lesion in the transition zone，and the percentage of positive needles in targeted biopsy are independent risk factors for pathological upgrading from Gleason score 3 + 3. The nomogram model constructed from these factors demonstrates good predictive performance and provides a reference for clinical decision-making.

As the globalization process accelerates and international medical exchanges become increasingly frequent, the status of foreign trainees in Chinese medical education system has become increasingly important. This paper explores the application of artificial intelligence technology in teaching vascular surgery for foreign trainees, including its specific application forms in theoretical teaching, surgical skill training, case analysis, and clinical decision-making. This article analyzes the advantages of integrating artificial intelligence into teaching foreign trainees, such as improving teaching efficiency, enhancing individualized teaching, and promoting cultural integration. Moreover, this paper discusses the challenges such as data security and privacy protection, technical reliability and adaptability, the transformation of educational concepts, and cross-cultural education, and proposes corresponding strategies to address these issues. The rational use of artificial intelligence technology is expected to improve the teaching quality of vascular surgery for foreign trainees and make a positive contribution to the cultivation of international medical talents.

OBJECTIVE To comprehensively evaluate the quality of Sanzi powder from different batches based on 12 components quantitative analysis combined with chemical pattern recognition and entropy weight-TOPSIS method.METHODS The contents of 12 components in 15 batches of Sanzi powder(No.S1-S15)were determined by HPLC-MS/MS,such as ethyl gallate,gallic acid,ferulic acid,corilagin,genipin-1-O-β-D-gentiobioside,toosendanin,geniposide,caffeic acid,methyl deacetylated coumarinate,tannic acid,rutin,quercetin.Cluster analysis(CA),principal component analysis(PCA),and orthogonal partial least squares-discriminant analysis(OPLS-DA)were conducted on the assay results.Using variable importance projection(VIP)value＞1 and P＜0.05 as the evaluation criteria,the quality differential markers in Sanzi powder were screened.The entropy weight method was used to calculate the weight value,and TOPSIS method was used to rank the quality of 15 batches of Sanzi powder from superior to inferior.RESULTS The contents of the 12 components were 13.494-24.292,2 069.608-3 188.100,1.410-3.616,1 065.030-2 630.584,1 404.704-1 838.078,101.640-354.268,9 193.720-14 777.854,1.240-5.060,148.028-5 541.990,4 261.422-5 607.438,107.560-195.512,2.226-4.192 μg/g,respectively.The results of CA,PCA and OPLS-DA indicated that 15 batches of Sanzi powder could be clustered into two groups.Specifically,batches S3,S7,S10 and S15 were grouped into one category,and remaining batches were grouped into one category.VIP values of geniposide,quercetin,caffeic acid,and methyl deacetylated coumarinate were all greater than 1,with corresponding P-values less than 0.05.The results of the entropy weight-TOPSIS analysis revealed that methyl deacetylate exhibited the smallest information entropy and the highest weight.The relative closeness degrees of samples S3,S7,S10 and S15 ranged from 0.789 to 0.973,while the remaining samples ranged from 0.054 to 0.172.CONCLUSIONS The contents of 12 components in Sanzi powder could be determined accurately by using HPLC-MS/MS technology.Methyl deacetylated coumarinate,geniposide,quercetin and caffeic acid were identified as the quality differential markers.It was found that the overall quality of samples S3,S7,S10 and S15 were superior to that of other batches.Notably,the quality of Gardeniae Fructus decoction pieces emerges as a critical factor in ensuring the consistency of the preparation's quality.

As the globalization process accelerates and international medical exchanges become increasingly frequent, the status of foreign trainees in Chinese medical education system has become increasingly important. This paper explores the application of artificial intelligence technology in teaching vascular surgery for foreign trainees, including its specific application forms in theoretical teaching, surgical skill training, case analysis, and clinical decision-making. This article analyzes the advantages of integrating artificial intelligence into teaching foreign trainees, such as improving teaching efficiency, enhancing individualized teaching, and promoting cultural integration. Moreover, this paper discusses the challenges such as data security and privacy protection, technical reliability and adaptability, the transformation of educational concepts, and cross-cultural education, and proposes corresponding strategies to address these issues. The rational use of artificial intelligence technology is expected to improve the teaching quality of vascular surgery for foreign trainees and make a positive contribution to the cultivation of international medical talents.

Objective:To explore the influencing factors for pathological upgrading in prostate cancer patients with a Gleason score of 3 + 3 undergoing targeted biopsy，and to establish a nomogram prediction model.Methods:A retrospective analysis was conducted on 191 patients with localized prostate cancer diagnosed with a Gleason score of 3 + 3 through targeted biopsies at the First Affiliated Hospital of Nanjing Medical University from January 2020 to June 2024. The age of the patients was 67（61，73）years，with prostate-specific antigen（PSA）level of 7.44（5.53，10.19）ng/ml，prostate volume of 35.64（26.59，48.97）ml，and PSA density（PSAD）of 0.20（0.14，0.31）ng/ml 2. Among them，61 cases（31.94%）had a Prostate Imaging Reporting and Data System（PI-RADS）score of 3，104 cases（54.45%）had a score of 4，and 26 cases（13.61%）had a score of 5. The diameter of the main lesion was 10.75（7.86，14.00）mm. The lesions were located in the peripheral zone in 78 cases（40.84%），the transition zone in 99 cases（51.83%），and the anterior fibromuscular stroma in 14 cases（7.33%）. The lesions were found at the apex in 56 cases（29.32%），in the body in 120 cases（62.83%），and at the base in 15 cases（7.85%）. MRI revealed only one lesion with a PI-RADS score ≥ 3 in 131 cases，two suspected lesions in 43 cases，three suspected lesions in 12 cases，and four suspected lesions in 5 cases. Systematic biopsy was positive in 121 cases（63.4%）and negative in 70 cases（36.6%）. The lesions were confined to the left lobe in 63 cases（32.98%），right lobe in 68 cases（35.60%），and involved both lobes in 60 cases（31.41%）. The interval between biopsy and surgery was 9.0（7.0，14.0）days. Univariate analyses were performed using Mann-Whitney U tests or χ2 tests，and multivariate logistic regression was used to identify independent predictors of pathological upgrading. A nomogram model was constructed based on these independent predictors. The model’s discriminative ability was assessed using the area under the receiver operating characteristic（ROC）curve（AUC），and internal validation of the model’s consistency was conducted using the bootstrap resampling method. Decision curve analysis（DCA）was performed to assess clinical utility. Results:Among the 191 cases，60（31.4%）had no pathological upgrading after surgery，while 131（68.6%）showed upgrading. Univariate analysis showed that the maximum diameter of the main lesion［9.0（6.0，13.2）mm vs. 11.0（8.4，14.0）mm］，number of suspicious lesions on MRI［1.0（1.0，1.0）vs. 1.0（1.0，2.0）］，number of positive systematic biopsy cores［1.0（0，2.0）vs. 1.0（0，3.0）］，percentage of positive systematic biopsy cores［0.08（0，0.17）vs. 0.12（0，0.25）］，number of positive targeted biopsy cores［2.0（1.0，3.0）vs. 3.0（1.0，4.0）］，percentage of positive targeted biopsy cores［0.37（0.24，0.75）vs. 0.50（0.38，0.85）］，level of the index lesion，location of the index lesion，and PI-RADS score were associated with pathological upgrading（ P < 0.05）. Multivariate logistic regression analysis showed that PI-RADS score 4（ OR = 5.88，95% CI 2.41 - 14.35），number of suspicious lesions on MRI（ OR = 4.15，95% CI 1.88 - 9.17），location of the index lesion in the transition zone（ OR = 6.86，95% CI 2.81 - 16.73），and percentage of positive targeted biopsy cores（ OR = 4.37，95% CI 1.38 - 14.90）were independent risk factors for pathological upgrading（ P < 0.05）. The nomogram model constructed using these predictors had an AUC of 0.845. Internal validation using the Bootstrap method yielded an AUC value of 0.812，indicating high predictive accuracy of the model. The calibration curve indicated good calibration. Decision curve analysis showed that the threshold range for net benefit in the model was between 12% - 100%. Conclusions:The PI-RADS score 4，the number of lesions with PI-RADS ≥ 3，the location of the main lesion in the transition zone，and the percentage of positive needles in targeted biopsy are independent risk factors for pathological upgrading from Gleason score 3 + 3. The nomogram model constructed from these factors demonstrates good predictive performance and provides a reference for clinical decision-making.

OBJECTIVE To establish fingerprint,chemical pattern recognition and multi-component quantification analysis of Sanzi powder,and evaluate its quality.METHODS HPLC method was adopted.The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition).Cluster analysis,principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted.The variable importance in projection(VIP)value greater than 1 was used as the index to screen the differential markers,and the contents of the differential markers were determined by the same HPLC method.RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated,and the similarities of them were 0.994-0.999;6 common peaks were identified,including gallic acid(peak 3),garminoside(peak 10),corilagin(peak 11),chebulinic acid(peak 16),ellagic acid(peak 18),crocin Ⅰ(peak 19).According to the results of cluster analysis,principal component analysis and orthogonal partial least squares-discriminant analysis,15 batches of samples could be clustered into two categories:S1,S5,S7,S9,S14 were clustered into one category;S2-S4,S6,S8,S10-S13,S15 were clustered into one category.VIP values of 11 differential components such as corilagin,chebulinic acid and ellagic acid were higher than 1.Among 15 batches of samples,the contents of corilagin,chebulinic acid and ellagic acid ranged 2.667-5.152,9.506-13.522,0.891-1.811 mg/g.CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple,and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition.Eleven components such as corilagin,chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.

Objective:To investigate the clinical efficacy of endovascular interventional therapy for spontaneous isolated superior mesenteric artery dissection(SISMAD).Methods:The retrospective cohort study was conducted. The clinical data of 87 patients with SISMAD who were admitted to The First Affiliated Hospital of Army Medical University from March 2012 to March 2023 were collected. There were 80 males and 7 femals, aged 54(49,61)years. Of 87 patients, 55 cases undergoing conservative therapy were allocated into conservative therapy group and 32 cases under-going endovascular interventional therapy were allocated into endovascular interventional therapy group. Observation indicators: (1) clinical characteristics; (2) treatment; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were represented as absolute numbers and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) clinical characteristics. There were significant differences in the cases with symptoms, percentage of neutrophils between the conservative therapy group and the endovascular interventional therapy group ( P<0.05). There was no significant difference in the proportion of Yun classification between the two groups ( P>0.05). (2)Treatment. There were significant differences in the complete vascular remodeling, duration of hospital stay, and total expenses between the conservative therapy group and the endovascular interventional therapy group ( χ2=23.752, t=-4.213, -16.421, P<0.05). There were 34 patients in the conservative therapy group and 24 patients in the endovascular interventional therapy group with relieved abdominal pain, respectively, showing no significant difference between the two groups ( P>0.05). For symptomatic patients in the conservative therapy group, symptoms including abdominal pain, nausea, vomiting, diarrhea, hematochezia were relieved or disappeared, and no intestinal ischemia or rupture occurred. For patients in the endovascular interventional therapy group, 30 cases were implanted stents, the operation time was 115(86,155)minutes, volume of intraoperative blood loss was 5(5,10)mL, dose of contrast media was (200±51)mL. There were 23, 8 and 1 cases with the contrast medium as Iodoxanol, Ioprosamide, Iodohexanol, respectively. About the surgical methods, 14 patients received single bare stent implantation, 3 cases received bare stent-assisted coil embolization, 10 cases received multiple bare stent implantation, 3 cases received covered stent implantation, 2 cases received angiography alone. A total of 39 self-expandable bare metal stents and 3 self-expandable covered stents were implanted. The diameter and length of the stents were (6.5±1.0)mm and (69±23)mm, respectively. Two asymptomatic patients had failure in endovascular interventional therapy and underwent superior mesenteric artery angiography. For the endovascular interventional therapy group, 92.3%(24/26) of patients were relieved abdominal pain and 2 patients with abdominal pain were improved after symptomatic treatment. (3) Follow-up. All the 87 patients were followed up for 12(4,24)months, without recurrent abdominal pain or secondary intervention. During the follow-up, 82 patients underwent computed tomography angiography or ultrasonography, and 5 patients had no available results. There was no SISMAD related death or superior mesenteric artery rupture. Eight patients in the conservative therapy group achieved complete vascular remodeling, versus 21 cases in the endovascular interventional therapy group, showing a significant difference between the two groups ( χ2=23.752, P<0.05). Conclusions:Compared with conservative therapy, patients undergoing endovascular interventional therapy for SISMAD has loner hospital stay, higher total costs, higher complete vascular remodeling rate. There is no recurrent abdominal pain in two methods.

AIM:To investigate the ameliorative effect of nociceptin/orphanin(N/OFQ)on anxiety-like be-havior in nicotine(NIC)withdrawal-induced rats and its regulatory mechanisms on the expression of neurotransmitters as-sociated with the hypothalamic-pituitary-adrenal(HPA)axis and inflammatory factors.METHODS:Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups:normal control group,NIC withdrawal model group,low-dose N/OFQ treatment group,and high-dose N/OFQ treatment group,with 8 rats in each group.To establish NIC with-drawal model,the rats in the NIC model and N/OFQ treatment groups were subcutaneously injected with NIC(0.4 mg/kg),twice a day for 7 consecutive days followed by 3 days of withdrawal.During the withdrawal period,the rats in the low and high-dose N/OFQ treatment groups received intracerebroventricular injection of N/OFQ(1 nmol or 10 nmol)once per day for 3 consecutive days.Ten minutes after the third administration,all rats underwent open filed(OF)and elevated plus maze(EPM)tests to detect behavioral changes.The serum concentrations of corticotrophin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone(CORT),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were measured by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in the central nu-cleus of the amygdala(CeA)of the brain were detected by RT-qPCR.Histological changes in neuron morphology in the CA1 region of the hippocampus were observed under a light microscope following hematoxylin and eosin(HE)staining.Norepinephrine(NE)levels in the CeA of the brain were determined by HPLC.The protein expression of tyrosine hydroxy-lase(TH)in the CeA of the brain was detected by Western blot.RESULTS:Compared with the NIC withdrawal model group,rats in the low and high-dose N/OFQ treatment groups showed significant increase in the distance and time spent in the central area of the open field(P<0.05 or P<0.01),as well as significant increase in the number of entries and the per-centage of time spent in the open arms of the EPM(P<0.05 or P<0.01).Furthermore,both low and high-dose N/OFQ treatment groups significantly inhibited serum concentrations of CRH,ACTH and CORT in NIC withdrawal rats(P<0.01).N/OFQ administration also significantly reduced the levels of inflammatory cytokines TNF-α,IL-1β,and IL-6 in the serum,as well as expression levels of TNF-α,IL-1β and IL-6 mRNA in the CeA(P<0.05 or P<0.01).The treatment with N/OFQ at both doses significantly alleviated neuronal damage in the CA1 region of the hippocampus and markedly re-duced thelevels of NE and TH protein expression in the CeA of NIC withdrawal rats(P<0.01).CONCLUSION:N/OFQ alleviates anxiety-like behavior in NIC withdrawal rats through mechanisms related to the regulation of HPA axis hormone levels and inflammatory factors.