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.

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.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

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.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

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.

AIM To study the chemical constituents from the large polar fraction of the roots of Lindera reflexa Hemsl.and their antitumor activities.METHODS The large polar fraction from the roots of L.reflexa was isolated and purified by silica gel column,Sephadex LH-20 gel column,semi-preparative HPLC and ODS medium pressure column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Thirteen compounds were isolated and identified as 2,6-dimethoxy-4-hydroxyphenyl-1-O-β-D-glucopyranoside(1),3-hydroxy-4,5-dimethoxyphenol-β-D-glucopyranoside(2),syringin(3),1-O-3,4-dimethoxy-5-hydroxyphenyl-(6-O-3,5-dimethoxygalloyl)-β-D-glucopyranoside(4),p-cymen-7-yl β-D-glucopyranoside(5),pisumionoside(6),staphylionoside D(7),dendranthemoside B(8),lynoiside(9),nudiposide(10),icariside B1(11),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(12),(+)-N-(methoxycarbonyl)-N-norboldine(13).Compounds 3 and 13 showed obvious cytotoxicity against human lung cancer cells(A549)and human gastric cancer cells(MGC80-3).CONCLUSION Compounds 1-13 are isolated from the roots of L.reflexa for the first time.Compounds 3 and 13 have good anti-tumor activities.

Objective To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty(TKA).Methods From February 2023 to July 2023,26 patients with unilateral knee osteoarthritis(KOA)were treated with TKA,including 4 males and 22 females,aged from 57 to 85 years old with an average of(67.58±6.49)years old;body mass in-dex(BMI)ranged from 18.83 to 38.28 kg·m-2 with an average of(26.43±4.15)kg·m-2;14 patients on the left side,12 pa-tients on the right side;according to Kellgren-Lawrence(K-L)classification,6 patients with grade Ⅲ and 20 patients with grade Ⅳ;the courses of disease ranged from 1 to 14 years with an average of(5.54±3.29)years.Images and videos of standing up and walking,walking side shot,squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation.The human posture estimation framework OpenPose were used to analyze stride frequency,step length,step length,step speed,active knee knee bending angle,stride length,double support phase time,as well as maximum hip flexion angle and maximum knee bending angle on squatting position.Western Ontario and McMaster Universities(WOMAC)arthritis index and Knee Society Score(KSS)were used to evaluate clinical efficacy of knee joint.Results All patients were followed up for 5 to 7 weeks with an average of(6.00±0.57)weeks.The total score of WOMAC decreased from(64.85±11.54)before op-eration to(45.81±7.91)at 6 weeks after operation(P＜0.001).The total KSS was increased from(101.19±9.58)before opera-tion to(125.50±10.32)at 6 weeks after operation(P＜0.001).The gait speed,stride frequency and stride length of the affected side before operation were(0.32±0.10)m·s-1,(96.35±24.18)steps·min-1,(0.72±0.14)m,respectively;and increased to(0.48±0.11)m·s 1,(104.20±22.53)steps·min-1,(0.79±0.10)m at 6 weeks after operation(P＜0.05).The lower limb support time and active knee bending angle decreased from(0.31±0.38)sand(125.21±11.64)° before operation to(0.11±0.04)s and(120.01±13.35)° at 6 weeks after operation(P＜0.05).Eleven patients could able to complete squat before operation,13 patients could able to complete at 6 weeks after operation,and 9 patients could able to complete both before operation and 6 weeks after operation.In 9 patients,the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation,and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation.Conclusion Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of pa-tients'gait.Knee pain of KOA was relieved and the function was improved,the supporting ability of the affected limb was im-proved after TKA,and the patient's stride frequency,stride length and stride speed were improved,and the overall movement rhythm of both lower limbs are more coordinated.

Objective:To investigate the efficacy and prognosis of different surgical approaches in sporadic medullary thyroid carcinoma.Methods:A retrospective analysis was conducted on 101 patients with sporadic medullary thyroid carcinoma (MTC) who underwent surgical treatment at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, from Feb. 2009 to Nov. 2023. The patients included 36 males and 75 females, with a male-to-female ratio of 1:2.1. The median age of the patients was 47 years old, with an age range of 21 to 72 years old. The study divided participants into two groups based on their surgical methods: an observation group (78 cases) and a control group (23 cases). The observation group received surgical methods in accordance with expert consensus, while the control group did not. The study compared the efficacy and prognosis of the two groups.Results:Statistical differences were found between the two groups in terms of stage II and III in TNM staging, intraoperative frozen pathological findings, number of lymph node resections in the central group, number of lymph node metastases in the central group, number of lymph node resections in the lateral cervical region, postoperative follow-up time, and five-year postoperative serum procalcitonin (Ctn) levels ( P<0.05) .Both groups of patients obtained a significant decrease in Ctn after surgical treatment. In the observation group, Ctn was at the remission level in 57 cases (73.1%), at the stable level in 13 cases (16.7%), and at the progression level in 8 cases (10.2%), while in the control group, Ctn was at the remission level in 20 cases (86.9%), at the progression level in 3 cases (13.1%), and there were no patients at the stable level after the operation.One patient (1.3 per cent) in the observation group had a recurrence after surgery; Two patients (8.7 per cent) in the control group had a recurrence. Conclusions:Standardised and thorough surgery can maximise the clearance of metastatic lymph nodes, effectively reduce the recurrence rate, achieve better efficacy, and improve the long-term prognosis of patients without increasing the risk of surgery and postoperative complications.