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.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

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 and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

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 compare the efficacy of early versus delayed reconstruction of anterior cruciate ligament (ACL) ruptures under arthroscopy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 260 young adults with ACL ruptures admitted to 940th Hospital of Joint Logistic Support Force of PLA from January 2022 to June 2024, including 171 males and 89 females, aged 18-45 years [(25.6±5.9)years]. Left knee was involved in 127 patients, while the right in 133 patients. All the patients underwent arthroscopic ACL reconstruction with autologous tendon grafts, of whom 130 patients were treated within 3 months after injury (early reconstruction group) but other 130 treated at 3 months after injury (delayed reconstruction group). The operative duration and intraoperative bleeding were compared between the two groups. The incidence of medial meniscus (MM) and lateral meniscus (LM) tears and the incidence of corresponding types of tears were recorded intraoperatively in the two groups. Tegner score and Lysholm score preoperatively, at 3 months postoperatively, and at the last follow-up were detected. Visual analogue scale (VAS) scores at 3 months postoperatively and at the last follow-up and postoperative complication rate were compared between the two groups.Results:All the patients were followed up for 6-15 months [(9.1±3.2)months]. There were no significant differences in operative duration or intraoperative bleeding between the two groups ( P>0.05). The incidence of MM tears in the early reconstruction group was 22.3% (29/130), lower than 34.6% (45/130) in the delayed reconstruction group ( P<0.05). There was no significant difference in the incidence of LM tears between the two groups ( P>0.05). The incidence of MM bucket-handle tears in the early reconstruction group was 2.3% (3/130), lower than 9.2% (12/130) in the delayed reconstruction group ( P<0.05), while no significant difference in the incidence of other types of meniscus tears was found between the two groups ( P>0.05). There were no significant differences in Tegner score or Lysholm score preoperatively between the two groups ( P>0.05). At 3 months postoperatively and at the last follow-up, the Tegner scores in the early reconstruction group were (7.4±1.3)points and (8.6±0.7)points, higher than (6.4±1.5)points and (7.9±0.6)points in the delayed reconstruction group and the Lysholm scores were (82.1±7.1)points and (90.7±3.8)points in the early reconstruction group, higher than (79.5±6.8)points and (86.3±4.0)points in the delayed reconstruction group ( P<0.01). There were no significant differences in VAS scores between the two groups at 3 months postoperatively or at the last follow-up ( P>0.05). The postoperative complication rate was 8.5% (11/130) in the early reconstruction group and 12.3% (16/130) in the delayed reconstruction group ( P>0.05). Conclusion:For young patients with ACL rupture, arthroscopic reconstruction within 3 months after injury can reduce the incidence of MM tear and bucket-handle tear and improve knee function without increasing the incidence of other complications when compared with delayed reconstruction at 3 months after injury.

BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P＞0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P＞0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P＜0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P＜0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P＞0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P＜0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P＜0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P＞0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P＜0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P＜0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P＜0.05),and that in the hip abductor muscle exercise group(22％)was significantly lower than that in the control group(45％).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.

BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P＞0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P＞0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P＜0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P＜0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P＞0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P＜0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P＜0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P＞0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P＜0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P＜0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P＜0.05),and that in the hip abductor muscle exercise group(22％)was significantly lower than that in the control group(45％).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.