Objective To compare the effectiveness of the heart rate variability threshold(HRVT),muscle oxygenation threshold(MOT),and their combined threshold(COMT)in predicting the ventila-tory threshold(VT)and lactate threshold(LT).Methods Twenty male athletes at or above the nation-al level were recruited to perform an incremental exercise test to determine VT and LT,during which gas exchange,muscle oxygenation,and heart rate variability were collected.The HRVT,MOT,and COMT methods were then applied,and their predictive validity was evaluated by comparing the correla-tions and agreements between heart rate(HR)and power output(PO)at VT and LT.Results For HR,VT1 showed strong correlation and agreement with MOT1(r=0.958,ICC=0.944)and COMT1(r=0.957,ICC=0.951),with COMT1 having the smallest mean bias(1.4 bpm)and the narrowest limits of agreement(LOA)(-5.4 to 8.2 bpm).Moreover,VT2 demonstrated the highest correlation and agree-ment with COMT2(r=0.985,ICC=0.982),with a mean bias of-0.7 bpm and LOA of-5.0 to 3.7 bpm.Meanwhile,LT showed high correlation and good agreement with COMT2(r=0.884,ICC=0.754)and MOT2(r=0.886,ICC=0.738),with mean biases of-6.8 bpm and-7.3 bpm,and LOA of-17.5 to 3.8 bpm and-17.9 to 3.2 bpm,respectively.For PO,VT1 had the best correlation and agreement with MOT1(r=0.836,ICC=0.808),with a mean bias of-0.2 W and LOA of-11.7 to 11.3 W.VT2 performed best correlation and agreement with COMT2(r=0.910,ICC=0.900),with a mean bias of 2.3 W and LOA of-8.9 to 13.5 W.In LT prediction,MOT2(r=0.736,ICC=0.692)outperformed COMT2(r=0.635,ICC=0.618),with mean biases of-2.6 W and 0.2 W,and LOA of-26.0 to 20.7 W and-26.6 to 27.1 W,respectively.Conclusion All three indicators—HRVT,MOT,and COMT—demonstrates high validity in predicting VT and LT.MOT1 performs best for predicting PO at VT1,while COMT2 shows the highest consistency for predicting both HR and PO at VT2.Howev-er,for LT prediction,MOT2 is more advantageous for predicting PO,whereas COMT2 is more accu-rate for predicting HR.Therefore,method selection should be tailored to the specific threshold type and measurement target.

Objective To compare the effectiveness of the heart rate variability threshold(HRVT),muscle oxygenation threshold(MOT),and their combined threshold(COMT)in predicting the ventila-tory threshold(VT)and lactate threshold(LT).Methods Twenty male athletes at or above the nation-al level were recruited to perform an incremental exercise test to determine VT and LT,during which gas exchange,muscle oxygenation,and heart rate variability were collected.The HRVT,MOT,and COMT methods were then applied,and their predictive validity was evaluated by comparing the correla-tions and agreements between heart rate(HR)and power output(PO)at VT and LT.Results For HR,VT1 showed strong correlation and agreement with MOT1(r=0.958,ICC=0.944)and COMT1(r=0.957,ICC=0.951),with COMT1 having the smallest mean bias(1.4 bpm)and the narrowest limits of agreement(LOA)(-5.4 to 8.2 bpm).Moreover,VT2 demonstrated the highest correlation and agree-ment with COMT2(r=0.985,ICC=0.982),with a mean bias of-0.7 bpm and LOA of-5.0 to 3.7 bpm.Meanwhile,LT showed high correlation and good agreement with COMT2(r=0.884,ICC=0.754)and MOT2(r=0.886,ICC=0.738),with mean biases of-6.8 bpm and-7.3 bpm,and LOA of-17.5 to 3.8 bpm and-17.9 to 3.2 bpm,respectively.For PO,VT1 had the best correlation and agreement with MOT1(r=0.836,ICC=0.808),with a mean bias of-0.2 W and LOA of-11.7 to 11.3 W.VT2 performed best correlation and agreement with COMT2(r=0.910,ICC=0.900),with a mean bias of 2.3 W and LOA of-8.9 to 13.5 W.In LT prediction,MOT2(r=0.736,ICC=0.692)outperformed COMT2(r=0.635,ICC=0.618),with mean biases of-2.6 W and 0.2 W,and LOA of-26.0 to 20.7 W and-26.6 to 27.1 W,respectively.Conclusion All three indicators—HRVT,MOT,and COMT—demonstrates high validity in predicting VT and LT.MOT1 performs best for predicting PO at VT1,while COMT2 shows the highest consistency for predicting both HR and PO at VT2.Howev-er,for LT prediction,MOT2 is more advantageous for predicting PO,whereas COMT2 is more accu-rate for predicting HR.Therefore,method selection should be tailored to the specific threshold type and measurement target.

Objective To explore the efficacy of high tibial osteotomy(HTO)combined with medial meniscus centraliza-tion in knee osteoarthritis.Methods A total of 26 patients who underwent surgery from October 2018 to October 2020 were re-viewed.Among them,14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group,including 8 males and 6 females,with an average age of(50.2±1.4)years old and follow-up time of(16.8±4.0)months.Twelve patients with high tibial osteotomy were in the control group,including 6 males and 6 females,with an average age of(50.9±1.8)years and follow-up time of(19.0±4.8)months.Operation time,the knee Lysholm score,knee 2000 IKDC score,MRI,femoral tibial angle(FTA),hip knee ankle angle(HKA),and intraoperative and postoperative compli-cations were recorded.Results All the incisions healed without any complication.The operation time in the centralized group was longer than that in the control group[(65.0±2.1)min vs(52.0±2.1)min,P＜0.05].The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[(2.8±1.4)mm vs(1.1±2.2)mm,P＜0.05].The FTA,HKA,knee Lyshlom score,and 2000 IKDC score between two groups were no significantly(P＞0.05).Postop-erative knee Lyshlom score and knee 2000 IKDC score improved in both groups(P＜0.05).Conclusion HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function.The medium and long-term curative effect still needs long-term follow-up of more cases.

Objective To investigate the relationship between the combined detection of lipoprotein-associated phospholipase A2(Lp-PLA2),protease activated receptor 2(PAR-2),and advanced oxidation protein products(AOPP)and the occurrence of in-stent restenosis after percutaneous coronary intervention(PCI),as well as its predictive value.Methods Patients with coronary heart disease after PCI were selected as the study objects.Group Ⅰ was the group without in-stent restenosis and group Ⅱ was the group with in-stent restenosis.The expressions of Lp-PLA2,PAR-2 and AOPP were detected by enzyme-linked immunosorbent assay(ELISA),and the predictive value and independent risk factors of these gene expression changes and the risk of in-stent restenosis were analyzed by receiver operating characteristic(ROC)analysis and binary logistic regression analysis.Results The blood Lp-PLA2 levels in group Ⅰ and group Ⅱ after 1 year follow-up after stenting were(190.24±33.67)and(256.14±37.68)ng·mL-1;PAR-2 levels were(1.41±0.38)and(1.95±0.43)ng·L-1,respectively;the AOPP levels were(47.25±4.62)and(58.76±4.86)μmol·L-1,respectively,and the differences were statistically significant(all P＜0.001).ROC analysis results showed that the truncation values of Lp-PLA2,PAR-2 and AOPP were 201.32 ng·mL-1,1.50 ng·mL-1 and 49.37 μmol·L-1,respectively.The area under the curve(AUC)was significantly higher than that detected alone(all P＜0.001).Binary logistic regression analysis shows that the independent risk factors for in-stent restenstenosis after PCI were Lp-PLA2 ≥ 201.32 ng·mL-1,PAR-2≥1.50 ng·L-1,AOPP ≥49.37 μmol·L-1 and LDL-C≥3.03 mmol·L-1,respectively(all P＜0.05).Conclusion The occurrence of in-stent restenosis after PCI is closely related to the increase in Lp-PLA2,PAR-2 and AOPP expression.

OBJECTIVE: To investigate whether the Runx2 gene can induce the differentiation of human amniotic mesenchymal stem cells (hAMSCs) to ligament fibroblasts in vitro and promote the tendon-bone healing in rabbits. METHODS: hAMSCs were isolated from the placentas voluntarily donated from healthy parturients and passaged, and then identified by flow cytometric identification. Adenoviral vectors carrying Runx2 gene (Ad-Runx2) and empty vector adenovirus (Ad-NC) were constructed and viral titer assay; then, the 3rd generation hAMSCs were transfected with Ad-Runx2 (Ad-Runx2 group) or Ad-NC (Ad-NC group). The real-time fluorescence quantitative PCR and Western blot were used to detect Runx2 gene and protein expression to verify the effectiveness of Ad-Runx2 transfection of hAMSCs; and at 3 and 7 days after transfection, real-time fluorescence quantitative PCR was further used to detect the expressions of ligament fibroblast-related genes [vascular endothelial growth factor (VEGF), collagen type Ⅰ, Fibronectin, and Tenascin-C]. The hAMSCs were used as a blank control group. The hAMSCs, hAMSCs transfected with Ad-NC, and hAMSCs were mixed with Matrigel according to the ratio of 1 : 1 and 1 : 2 to construct the cell-scaffold compound. Cell proliferation was detected by cell counting kit 8 (CCK-8) assay, and the corresponding cell-scaffold compound with better proliferation were taken for subsequent animal experiments. Twelve New Zealand white rabbits were randomly divided into 4 groups of sham operation group (Sham group), anterior cruciate ligament reconstruction group (ACLR group), anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-NC-scaffold compound group (Ad-NC group), and anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-Runx2-scaffold compound group (Ad-Runx2 group), with 3 rabbits in each group. After preparing the ACL reconstruction model, the Ad-NC group and the Ad-Runx2 group injected the optimal hAMSCs-Matrigel compunds into the bone channel correspondingly. The samples were taken for gross, histological (HE staining and sirius red staining), and immunofluorescence staining observation at 1 month after operation to evaluate the inflammatory cell infiltration as well as collagen and Tenascin-C content in the ligament tissues. RESULTS: Flow cytometric identification of the isolated cells conformed to the phenotypic characteristics of MSCs. The Runx2 gene was successfully transfected into hAMSCs. Compared with the Ad-NC group, the relative expressions of VEGF and collagen type Ⅰ genes in the Ad-Runx2 group significantly increased at 3 and 7 days after transfection ( P<0.05), Fibronectin significantly increased at 3 days ( P<0.05), and Tenascin-C significantly increased at 3 days and decreased at 7 days ( P<0.05). CCK-8 detection showed that there was no significant difference ( P>0.05) in the cell proliferation between groups and between different time points after mixed culture of two ratios. So the cell-scaffold compound constructed in the ratio of 1∶1 was selected for subsequent experiments. Animal experiments showed that at 1 month after operation, the continuity of the grafted tendon was complete in all groups; HE staining showed that the tissue repair in the Ad-Runx2 group was better and there were fewer inflammatory cells when compared with the ACLR group and the Ad-NC group; sirius red staining and immunofluorescence staining showed that the Ad-Runx2 group had more collagen typeⅠ and Ⅲ fibers, tending to form a normal ACL structure. However, the fluorescence intensity of Tenascin-C protein was weakening when compared to the ACLR and Ad-NC groups. CONCLUSION Runx2 gene transfection of hAMSCs induces directed differentiation to ligament fibroblasts and promotes tendon-bone healing in reconstructed anterior cruciate ligament in rabbits.
Pregnancy ; Female ; Humans ; Rabbits ; Animals ; Vascular Endothelial Growth Factor A/metabolism* ; Fibronectins/metabolism* ; Collagen Type I/genetics* ; Tenascin/metabolism* ; Collagen/metabolism* ; Anterior Cruciate Ligament/surgery* ; Mesenchymal Stem Cells ; Tendons/metabolism* ; Fibroblasts/metabolism*

Breast cancer is currently one of the caneers with the highest incidence.Clinically, most breast eaneer patients often die due to distant metastasis.In the complex easeade of metasta¬sis, the formation of the pre-metastasis niche ( PMN) has been considered to he cnrcial in the process of distant metastasis of tumors in recent years.Tumors at the primary site secrete tumor- derived secretory factors (TDSF) , extracellular vesicles ( EV) and so on to metastasize target organs.thereby changing the mi- croenvironment of the target organs to adapt to the subsequent distant metastasis of the tumor.Breast cancer is a kind of cancer number of studies have revealed the mechanism of the breast cancer pre-metastatic niche, showing that inhibiting the PMN can reduce breast cancer metastasis.The multi-target and multi- component features of traditional Chinese medicine have been re¬ported to effectively interfere with the formation of PMN.This review summarizes the breast cancer's mechanism of lung pre- metastatic niche formation and traditional Chinese medicine in¬tervention.

Arm ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Carboplatin ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Humans ; Maintenance Chemotherapy ; Ovarian Neoplasms ; Prognosis ; Quality of Life ; Recombination, Genetic ; Sample Size

Sepsis is a common clinical critical disease, which is one of the main causes of septic shock and multiple organ dysfunction syndrome (MODS). Since traditional clinical interventions are simple and limited, the mortality of sepsis remains high and is also one of the main causes of death of intensive care unit (ICU) patients. Nicotinamide has a wide range of cytoprotective effects. A large number of studies have shown that nicotinamide can play an important role in infection and sepsis by repairing mitochondrial function to restore adenosine triphosphate (ATP) level, inhibiting poly (ADP-ribose) polymerase (PARP) activation, inhibiting proinflammatory mediators and antioxidant damage. This article reviews the pathogenesis of sepsis and the role of nicotinamide in sepsis treatment, aiming to provide references for exploring new therapeutic directions and effective therapeutic measures for sepsis.

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. Conclusions Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.