Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Calcitonin-negative medullary thyroid carcinoma(CNMTC)is a rare subtype of medullary thyroid carcinoma,characterized by normal serum calcitonin levels,which often leads to misdiagnosis or missed diagnosis.The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives.Diagnostic approaches include ultrasound-guided fine needle aspiration cytology,serum CEA and ProGRP measurements,and RET gene testing.Surgical resection remains the mainstay of treatment,while neoadjuvant therapy may be considered in selected cases.This review summarizes recent advances in the understanding,diagnosis,treatment,and prognosis of CNMTC,aiming to provide clinical guidance for better management of this challenging condition.

OBJECTIVE To investigate the activity and mechanism of tetrandrine(TET)against influenza A virus in vitro and in vivo.METHODS(1)Cell experiments.① Human non-small cell lung cancer cells(A549)were divided into TET 0(cell control),1.25,2.5,5,10,20 and 25 μmol·L-1 groups,and H1N1+TET 0,1.25,2.5,5,10,20 and 25 μmol·L-1 groups.The TET groups were treated with the corresponding concentrations of TET while the H1N1+TET groups were infected with H1N1 for 1 h before the corresponding concentrations of TET were added.After 48 h,cell viability was detected using the CCK-8 method.② The cells were divided into cell control,H1N1+TET 0,2.5,5,and 10 μmol·L-1 groups and treated as in ①.After 24 h of incubation,the mRNA expressions of matrix protein 1(M1),hemagglutinin(HA),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-β(IFN-β)were tested by the real-time quantitative PCR(RT-qPCR).The expression levels of M1,HA,neuraminidase(NA),nucleoprotein(NP),and phosphorylation of signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.(2)Animal experiments.① Male BALB/c mice were randomly divided into the solvent control group,H1N1 group,H1N1+oseltamivir phosphate(Ose)20 mg·kg-1 group,and H1N1+TET 25,50 and 100 mg·kg-1 groups.The solvent control group and the H1N1 group were ig administered with 0.5％carboxymethyl cellulose sodium(CMC-Na),while the H1N1+Ose group and the H1N1+TET 25,50 and 100 mg·kg-1 groups were ig given suspensions of the respective concentrations of drugs in 0.5％CMC-Na.After three consecutive days of pretreatment,all these groups except the solvent control group were intranasally inoculated with H1N1 to establish an influenza-infected mouse model.The survival rate and body mass of mice were monitored and recorded for 15 consecutive days post-H1N1 infection.② The grouping and treatment were the same as ①.After infection,mice were sacrificed on day 3 and 5.The expression levels of M1,HA,TNF-α,IL-1βand IL-6in lung tissues were detected by RT-qPCR,and those of M1,HA,NA,NP,and phosphoryla-tion of STAT3 protein in mice lung tissues by Western blotting.Hematoxylin-Eosin(HE)staining was performed to observe the pathological changes of lung tissues in mice.The levels of IL-6,TNF-α and IFN-β in bronchoalveolar lavage fluid(BALF)were determined by enzyme-linked immunosorbent assays(ELISA).RESULTS(1)① The half maximal inhibitory concentration study showed a value of 18.06 μmol·L-1 for A549 effected by TET.Compared with the H1N1 group,TET 2.5,5 and 10 μmol·L-1 significantly increased cell viability.② The expression levels of M1,HA mRNA and M1,HA,NA protein in the TET 2.5,5 and 10 μmol·L-1 groups were significantly lowered compared with the H1N1 group.TET 5 μmol·L-1 significantly decreased H1N1-induced IL-6,TNF-α and IFN-β mRNA expression levels in A549 cells.TET 5 and 10 μmol·L-1 could significantly mitigate the phosphorylation of STAT3.(2)① Com-pared with the H1N1 group,TET 50 mg·kg-1 significantly improved the survival rate of H1N1-infected mice while TET 25 mg·kg-1 significantly elevated the body-weight of H1N1-infected mice.In the TET 50 mg·kg-1 group,expressions of HA and M1 mRNA,and HA,M1,NA and NP protein in the lung tissues of H1 N1-infected mice were significantly reduced compared with the H1N1 group.Compared with the H1N1 group,TET 50 mg·kg-1 significantly decreased the lung index,improved inflammatory lesions in lung tissues,inhibited the mRNA expressions of TNF-α,IL-6 and IFN-β in lung tissues,and down regu-lated the expressions of TNF-α,IL-6 and IFN-β proinflammatory cytokines in the BALF of the H1N1-infected mice.In addition,TET 50 mg·kg-1 also significantly inhibited STAT3 phosphorylation in lung tissues of mice infected with H1N1.CONCLUSION TET can inhibit H1N1 infection both in vivo and in vitro.The potential mechanism may be related to the inhibition of the IL-6/STAT3 pathway,which subse-quently suppresses the inflammatory response induced by H1N1.

Objective To evaluate the safety and efficacy of transcatheter mitral valve-in-valve replacement(ViV-TMVR)in the treatment of bioprosthetic mitral valve failure.Methods Seventeen patients with bioprosthetic mitral valve failure who required ViV-TMVR were selected.Preoperative data including age,gender,body mass index(BMI),usage time of bioprosthetic mitral valve,comorbidities(hypertension,coronary heart disease,old cerebral infarction,atrial fibrillation and diabetes)and New York Heart Association(NYHA)functional class were recorded,and left ventricular end-diastolic diameter(LVEDD),right atrial diameter(RA),pulmonary artery systolic pressure(PASP),left ventricular ejection fraction(LVEF),type of bioprosthetic mitral valve failure,degree of bioprosthetic mitral valve regurgitation and stenosis,peak velocity and mean transvalvular pressure gradient of the bioprosthetic mitral valve,and Society of Thoracic Surgeons(STS)score were also collected.Intraoperative data included puncture route,valve type,intraoperative complications,operation time and immediate postoperative transesophageal echocardiography(TEE)assessment(peak velocity and mean transvalvular pressure gradient of the valve-in-valve,valve-in-valve regurgitation or paravalvular regurgitation)were collected.Postoperative data included time in the intensive care unit(ICU)/cardiovascular intensive care unit(CCU),total postoperative hospital stay and 30-day postoperative echocardiographic results and NYHA functional class were recorded.Patients were divided into the domestic NewMed valve group(10 cases)and the imported Edwards valve group(7 cases)based on the type of valve used.The safety and efficacy of ViV-TMVR were analyzed,and the efficacy of domestic valves and imported valves was compared.Results All 17 patients successfully underwent ViV-TMVR via the transseptal approach without serious complications,and the 30-day readmission rate was 0%.There were no significant differences in operation time of domestic valves and imported valves,mild paravalvular regurgitation of the valve-in-valve,peak velocity and mean transvalvular pressure gradient of the valve-in-valve immediately after surgery and at 30-day postoperatively,time in ICU/CCU,total postoperative hospital stay and the proportion of patients with NYHA functional class Ⅲ-Ⅳ at 30-day postoperatively between the domestic valve group and the imported valve group.During the 30-day follow-up,one patient died of cerebral hemorrhage,and one patient had major adverse cardiovascular events(MACE,cerebral hemorrhage).Compared with before the operation,the peak velocity and mean transvalvular pressure gradient of the valve-in-valve,LVEF,and PASP decreased immediately after surgery and at 30 days after surgery.Compared with immediately after surgery,the peak velocity and mean transvalvular pressure gradient of the valve-in-valve increased at 30 days postoperatively(P＜0.01),while there were no significant differences in LVEF and PASP.Conclusion Transseptal ViV-TMVR is safe and effective in the short term for patients with bioprosthetic mitral valve failure who are at high risk of re-thoracotomy,and the efficacy of domestic valves is comparable to that of imported valves.

Objective:To investigate the risk factors for detecting clinically significant prostate cancer (CSPCa) in patients with Prostate Imaging Reporting and Data System (PI-RADS) score≤3 on multi-parameter magnetic resonance imaging (mpMRI).Methods:Retrospective analysis was performed on the case data of 335 patients with suspected prostate cancer and PI-RADS score ≤3 who were admitted to Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2022. All patients underwent 24-needle prostate biopsy. Clinical data such as age, body mass index, past medical history, serological laboratory indicators, and mpMRI imaging data were collected. The patients were grouped according to whether the puncture pathology was CSPCa or not, and the differences in clinical data between the two groups were analyzed by t-test, rank sum test and Chi-test. Multivariate Logistic regression analysis was further used to determine independent risk factors for MRI invisible prostate cancer, and receiver operating characteristics (ROC) curves were drawn. At the same time, further subgroup analysis was conducted based on whether prostate-specific antigen (PSA) was positive before puncture and PI-RADS score, respectively, and the same statistical method was used to further determine the influence of different serological indicators and PI-RADS score on the analysis results of risk factors. Results:Among all patients, 81 were CSPCa patients and 254 were non-CSPCa patients. Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) and PI-RADS score of 3 were independent risk factors for MRI invisible prostate cancer. At the same time, compared with suspected lesions located only in the transitional zone, the incidence of CSPCa in patients with suspected lesions located in the peripheral zone would increase, and the incidence of CSPCa would further increase when suspected lesions were found in both the transitional zone and the peripheral zone. In PSA-negative patients, only suspected lesion location was an independent risk factor for MRI invisible prostate cancer, while in PSA-positive patients, prostate volume, PSAD, and PI-RADS scores were independent risk factors. In subgroup analysis with different PI-RADS scores, suspicious lesions in both the transitional zone and peripheral zone indicate a higher likelihood of CSPCa. For patients with PI-RADS scores of 1 to 2, suspicious lesions in the peripheral zone alone may also indicated CSPCa, while for patients with PI-RADS scores of 3, the lower free prostate-specific antigen/total prostate-specific anti-principle was more accurate in predicting CSPCa.Conclusions:For patients who are clinically suspected of prostate cancer but whose PI-RADS score is less than or equal to 3 points indicated by mpMRI, it is necessary to further focus on the results of different serological indicators according to whether their PSA is positive and PI-RADS score respectively to judge whether patients should receive systemic prostate puncture, instead of using PSA level as a single indication for puncture. At the same time, clinicians should also pay full attention to the location of suspected lesions, when they are located in the peripheral zone, or there are suspected lesions in both the peripheral zone and the transitional zone, the possibility of CSPCa should be fully considered.

Chimeric antigen receptor-modified T(CAR-T)cell therapy,as a new type of cellular immunotherapy,has shown good clinical efficacy in the treatment of malignant hematological tumors,especially B-cell acute lympho-blastic leukemia.However,there are problems such as antigen loss and immune evasion in single-target selection,so multi-target therapy strategies are gradually gaining attention.Multi-target CAR-T can effectively avoid antigen escape caused by a single target by targeting multiple tumor-associated antigens at the same time,reduce the risk of recurrence,and is expected to improve the therapeutic effect.This paper primarily discusses the structural types of multi-target CAR-T cell therapy and its clinical trial applications in the treatment of B-cell acute lymphoblastic leu-kemia(B-ALL),aiming to provide future references for the treatment of B-ALL.

Objective:To explore the independent risk factors for chemoresistance during gemcitabine plus cisplatin (GC) adjuvant chemotherapy in patients with locally advanced bladder cancer after radical cystectomy and to construct a related predictive model.Methods:The clinical data of 228 patients with locally advanced bladder cancer who received GC chemotherapy after radical cystectomy at Beijing Friendship Hospital, Capital Medical University, from January 2013 to June 2024 were retrospectively analyzed. Among them, 184 were males, and 44 were females, with an average age of (68.8±10.6)years and an average body mass index (BMI) of (24.2±3.6)kg/m 2. According to tumor progression during chemotherapy, patients were divided into a chemotherapy-resistant(CR) group ( n=59) and a non-chemotherapy-resistant(NCR) group ( n=169). Independent sample t-test, chi-square test, and non-parametric test were used to compare general clinical characteristics and relevant examination results during chemotherapy between the two groups. Multivariate linear regression analysis was used to identify independent risk factors for GC chemoresistance. Propensity score matching (PSM) was used to match the TNM stage data between the two groups, and Kaplan-Meier and log-rank tests were used to compare overall survival(OS)after matching. Results:The median number of chemotherapy cycles was 3 in the CR group and 4 in the NCR group. Compared with the NCR group, CR patients were younger [(66.3±9.4) years vs.(69.7±10.9)years], had a higher proportion of kidney transplantation history[6.8%(4/59) vs. 0.6%(1/169)], hypertension [50.8%(30/59) vs. 36.1%(61/169)], coronary heart disease[23.7%(14/59) vs.9.5% (16/169)], and hydronephrosis [13.6%(8/59) vs. 4.1%(7/169)](all P<0.05). CR patients had a higher proportion of T 4 stage [20.3% (12/59) vs. 5.9% (10/169)], N 2 stage [42.4% (25/59) vs. 8.3% (14/169)], multifocal tumors at initial diagnosis [59.3% (35/59) vs. 26.6% (45/169)], and larger maximum tumor diameter [2.5 (1.5, 3.4) cm vs. 1.6 (1.2, 2.5) cm] (all P < 0.05). The CR group showed higher proportions of long-term urinary tract infection (UTI) [90.1% (53/59) vs. 7.7% (15/169)], higher systemic immune-inflammation index (SII) [991.6 (451.0, 1577.9) vs. 462.8 (309.0, 766.7)], absolute neutrophil count [6.5(4.1, 7.8)× 10 9/L vs. 3.9 (2.9, 5.1)× 10 9/L], and platelet count [(220.0 ± 96.2)× 10 9/L vs. (191.0 ± 64.8)× 10 9/L], but lower albumin levels [(34.3 ± 4.2) g/L vs. (39.9 ± 3.8) g/L] and albumin-to-globulin ratio (A/G) [(1.2 ± 0.3) vs. (1.3 ± 0.2)] (all P < 0.05). Multivariate linear regression analysis identified only T stage and long-term UTI as independent risk factors for GC chemoresistance( P<0.05).The probability of GC chemoresistance in bladder cancer patients was calculated as: P(Chemoresistance)=[0.155×T stage+ 0.624×(long-term UTI)]×100%(long-term UTI = 1 if present during chemotherapy, otherwise=0). After PSM, survival analysis showed that the median OS was significantly higher in the NCR group (55 months) than that in the CR group (30 months) ( P=0.020). Conclusions:This study demonstrates that advanced T stage and persistent UTI are independent risk factors for GC chemotherapy resistance in locally advanced bladder cancer patients. Based on these findings, a predictive model for chemotherapy resistance probability was constructed using multivariate linear regression analysis.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People