Objective To investigate whether 3D-guided cone-shaped segmentectomy can achieve comparable long-term outcomes with lobectomy for deep early-stage lung cancer with diameter≤2 cm. Methods We retrospectively screened patients with deep early-stage non-small cell lung cancer (NSCLC) with diameter≤2 cm who underwent lobectomy or segmentectomy in the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018. All pulmonary segmentectomy was performed using 3D-guided cone-shaped segmentectomy with segment or subsegment as the resection unit. Univariate and multivariate regression analyses were performed by Cox proportional hazard regression model. The patients who underwent segmentectomy and lobectomy were matched 1∶1 by propensity-score matching analysis. The oncological outcomes of two groups were compared. Results Our cohort was divided into a segmentectomy group (n=222) and a lobectomy group (n=127). The age, total nodule size, solid component size and proportion of pure solid nodule in the lobectomy group were significantly higher than those in the segmentectomy group. The median follow-up time was 49 months. Surgical margins were negative in all patients. The local recurrence rate of segmentectomy was 0.45%. The disease-free survival (DFS) rate and overall survival (OS) rate of patients in the segmentectomy group were significantly better than those in the lobectomy group (5-year DFS rate: 98.64% vs. 89.77%, P<0.001; 5-year OS rate: 99.55% vs. 92.10%, P<0.001). Multivariate regression analysis showed that the differences between two groups were not significant [DFS rate: HR=0.52. 95%CI (0.11, 2.59), P=0.427; OS rate: HR=0.08. 95%CI (0.00, 3.24), P=0.179] after adjusting for other factors. After propensity score matching, 77 patients were preserved in both segmentectomy group and lobectomy group, with the mean nodule size of 1.44 cm and 1.49 cm and the mean consolidation tumor ratio (CTR) of 0.46 and 0.52, respectively. There was no statistical difference in DFS rate (P=0.640) or OS rate (P=0.310) between the two groups. Conclusion 3D-guided cone-shaped segmentectomy can be an acceptable treatment for low-grade malignant NSCLC deep in lung parenchyma with diameter≤2 cm, and its oncology effect is not inferior to lobectomy.

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P＜0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.

Segmental bone defects and nonunion of fractures caused by trauma,infection,tumor or systemic diseases with limited osteogenesis and prolonged bone healing cycles are challenging issues in orthopedic clinical practice.Therefore,identifying regulatory factors for bone tissue regeneration and metabolism is crucial for accelerating bone repair and reconstructing defective areas.Silence information regulator 6(SIRT6),functioning as a deacetylase and nucleotide transferase,is extensively involved in the regulation of differentiation,apoptosis,metabolism,and inflammation in bone cells including osteoblasts and osteoclasts,and is considered to be an important factor in regulating bone metabolism.SIRT6 forms a complex with B lymphocyte-induced maturation protein 1(Blimp1),down-regulates the expression of the nuclear factor κB(NF-κB)pathway,and promotes the expression of the ERα-FasL axis signal to inhibit osteoclast formation and maturation differentiation,thereby hindering bone resorption and increasing bone mass.In addition,SIRT6 activates the Akt-mTOR pathway to regulate the autophagy level and osteogenesis of bone marrow mesenchymal stem cells,inhibits glycolysis and reactive oxygen production in osteoblasts,promotes osteoblast differentiation through the CREB/CCN1/COX2 pathway and the bone morphogenetic protein(BMP)signaling pathway,enhances bone formation,and accelerates bone regeneration and repair of skeletal tissue.This article provides an overview of the research progress on SIRT6 in the pathophysiology of bone regeneration,revealing its potential as a novel therapeutic target for bone tissue repair to alleviate the progression of skeletal pathological diseases.

Objective : To analyze the correlation between Ki⁃67 expression and EGFR mutations in lung adenocarcinoma and reveal their prognostic roles. Methods : This study retrospectively screened lung adenocarcinoma patients who underwent surgical treatment between 2014 and 2020 in our department. Clinicopathological characteristics , Ki⁃67 expression and EGFR mutations were collected. The chi⁃square , Student ’s t ⁃test and ANOVA were used for the comparison of Ki⁃67 expression and EGFR mutations among the groups. The Spearman ’s rho was adopted to evaluate the correlation between Ki⁃67 expression and EGFR mutations. Finally , the Log⁃rank test was used to reveal the prognostic roles of Ki⁃67 expression and EGFR mutations in lung adenocarcinoma. Results : A total of 673 lung adenoca~rcinoma samples were enrolled in this study. The mean expression of Ki⁃67 was 21. 37 ± 20. 43 [ Median : 15(6 30)] . Among these subjects , 462 samples harbored EGFR mutations (68. 65% ) . The expression of Ki⁃67 was much higher in males and smokers , and was positively correlated with tumor size and lymph node metastasis. The frequency of EGFR mutations was higher in females and non⁃smokers , and was negatively correlated with tumor size and lymph node metastasis. Samples with EGFR mutations had a lower Ki⁃67 expression level than those without EGFR mutations ( 18. 82 ± 17. 75 vs 26. 97 ± 24. 45 , P < 0. 001) . Consistently , the frequency of EGFR mutations in samples with a lower expression level of Ki⁃67 was significantly higher than that in patients with a higher Ki⁃67 expression (74. 1% vs 57. 0% , P < 0. 001) . The Spearman ’s rho analysis indicated that a higher Ki-67 expression and EGFR wild type were significantly associated with a poorer prognosis of lung adenocarcinoma ( P <0. 05 ). The combined analysis of Ki-67 expression and EGFR mutations indicated that EGFR wild type patients with Ki-67 > 10 had a poorer prognosis than subjeets with Ki-67 <10 and EGFR mutations. What's more , the HR value was 4. 46 (95% CI: 1. 91 10. 73 , P < 0. 001) . Conclusion Ki⁃67 expression was significantly negatively correlated with EGFR mutations in lung adenocarcinoma. Ki⁃67 expression and EGFR mutations might have a combined effect on the prognosis of lung adenocarcinoma.

Objective To investigate the value of dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating therapeutic response of hepatoma treated with radiofrequency ablation (RFA).Methods Totally 48 cases of patients with hepatic carcinoma (48 lesions) admitted in Xiangya Hospital of Central South University from September 2012 to January 2014 were selected.All patients underwent radiofrequency ablation,of which 30 patients were diagnosed by pathology after surgery,18 patients by clinical diagnosis.All patients underwent two-dimensional contrast-enhanced ultrasound (2D-CEUS) and 3D-CEUS 1 month and 3 months after RFA treatment to evaluate the therapeutic response,and the results of contrast-enhanced ultrasound and enhanced computed tomography (CT) [or magnetic resonance imaging (MRI)] were compared.The final diagnostic results of pathologic biopsy or more than two imaging examinations [ultrasonography,CT,MRI,positron emission tomography (PET)],tumor markers,and more than 3 months follow-up of patients were used as the gold standard.The sensitivity,specificity and accuracy of dynamic 3D-CEUS,2D-CEUS,enhanced CT (or MRI) in the diagnosis of tumor inactivation were calculated respectively.Results After radiofrequency ablation,dynamic 3D-CEUS could provide more valuable information in 75.0％ (36/48) lesions,which contribute to assess the efficacy of radiofrequency ablation.While compared with 2D-CEUS,3D-CEUS did not change the diagnosis or clinical management in 12 (25.0％) lesions.40 of 48 lesions were found no-enhancement in entire CEUS procedure suggesting that the tumor completely inactivated,while 8 lesions showed local enhancement on the edge of lesion suggesting that part of the tumors were active.39 of 48 lesions showed no-enhancement and other 9 with irregular enhancement on enhanced CT (or MRI).The sensitivity,specificity and accuracy of CEUS and enhanced CT (or MRI) in detection of residual tumor after radiofrequency ablation were 80.0％,100％,95.8％ and 80.0％,97.4％,93.8％,respectively.Conclusions There was no statistical significance among 3D-CEUS,2D-CEUS and enhanced CT or MRI in evaluating therapeutic response of hepatoma treated with radiofrequency ablation.But 3D-CEUS can provide more valuable information,3D-CEUS has potential usefulness in the evaluation of percutaneous radiofrequency ablation of hepatic tumors.

Objective To develop an UPLC-MS/MS method for simultaneously determination of five components (adenosine,cytidine,guanosine,mannitol and adenine) in Qiangshenpaidu capsules. Methods The UPLC separation was performed on an Agilent ZOBAX SB-C18(2.1 mm×150 mm,5 μm) column.Isocratic elution was carried out with mobile phase consisting of methanol-0.1%formic acid (5∶95) at a flow rate of 0.2 mL.min-1.The mass spectrometer was operated in the positive ionization electrospray ( ESI) mode using multiple monitoring ( MRM) for analysis of five components. Results Adenosine,cytidine,guanosine,mannitol and adenine were all analyzed with good precision and accuracy. The linear ranges were 35-1 120 ng.mL-1( r=0.998 1) ,10-320 ng.mL-1( r=0.996 4) , 30-980 ng.mL-1( r=0.999 3) , 40-1 280 ng.mL-1( r=0.993 4), 25-800 ng.mL-1(r=0.996 5),respectively.The recoveries of six analytes ranged from 97.4% to 103.6% and the relative standard deviations were all below 4.7%. Conclusion A sensitive,accurate and suitable UPLC-MS/MS method has been developed,and the method could be applied for the determination of adenosine,cytidine,guanosine,mannitol,and adenine in Qiangshenpaidu Capsules.

OBJECTIVEThe aim of this study was to identify six miRNAs expressed in plasma of patients with pancreatic cancer (PCa) and analyze their value as a diagnostic index of pancreatic cancer.

METHODSPlasma total RNAs were extracted from 30 PCa patients and 26 normal controls, and the abundance of six microRNAs was measured using real-time PCR. The possibility to combine them with CA19-9 as diagnostic biomarkers was analyzed.

RESULTSThe expression level of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a in plasma of patients with pancreatic cancer were 1.65×10(6), 5.98×10(4), 2.83×10(3), 3.47×10(6), 2.76×10(6), and 1.03×10(3) (copies/µl), while the normal controls were 4.08×10(5), 2.54×10(4), 8.55×10(2), 1.79×10(6), 9.32×10(5), and 4.67×10(2) (copies/µl), respectively, with a significant difference between the two groups (P < 0.05). The areas under the ROC curve of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a were 0.893, 0.810, 0.820, 0.766, 0.816 and 0.729, respectively. MiR-21 had the highest diagnostic value when it was used as diagnostic marker alone. The combination of miR-155 and miR-25 was more effective to distinguish PCa from normal than to be used alone, and the area under the ROC curve was 0.913 (95%CI 0.838-0.988) .When CA199 associated with miR -210 and miR-25, respectively, the areas under the ROC curves were 0.96 (95%CI was 0-1.0) and 0.942 (95% CI was 0.876-1.0), which were higher than CA199 alone (0.862, 95%CI was 0.748-0.975). There was a high improvement in diagnostic sensitivity and accuracy when miR-210 and miR-25 were combined with CA19-9, respectively.

CONCLUSIONSPlasma miR-21, miR-155, miR-25, miR-210 have diagnostic value for pancreatic cancer, and deserve further study.

Aged ; Biomarkers, Tumor ; blood ; genetics ; CA-19-9 Antigen ; blood ; Case-Control Studies ; Female ; Humans ; Male ; MicroRNAs ; blood ; Middle Aged ; Pancreatic Neoplasms ; blood ; diagnosis ; genetics ; ROC Curve ; Real-Time Polymerase Chain Reaction

Objective The aim of this study was to identify six miRNAs expressed in plasma of patients with pancreatic cancer ( PCa ) and analyze their value as a diagnostic index of pancreatic cancer . Methods Plasma total RNAs were extracted from 30 PCa patients and 26 normal controls, and the abundance of six microRNAs was measured using real-time PCR.The possibility to combine them with CA19-9 as diagnostic biomarkers was analyzed .Results The expression level of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a in plasma of patients with pancreatic cancer were 1.65 ×106 , 5.98 × 104, 2.83 ×103, 3.47 ×106, 2.76 ×106, and 1.03 ×103 (copies/μl), while the normal controls were 4.08 ×105, 2.54 ×104, 8.55 ×102, 1.79 ×106, 9.32 ×105, and 4.67 ×102(copies/μl), respectively, with a significant difference between the two groups (P<0.05).The areas under the ROC curve of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a were 0.893, 0.810, 0.820, 0.766, 0.816 and 0.729, respectively.MiR-21 had the highest diagnostic value when it was used as diagnostic marker alone . The combination of miR-155 and miR-25 was more effective to distinguish PCa from normal than to be used alone, and the area under the ROC curve was 0.913(95%CI 0.838-0.988).When CA199 associated with miR-210 and miR-25, respectively, the areas under the ROC curves were 0.96 (95%CI was 0-1.0) and 0.942(95% CI was 0.876-1.0), which were higher than CA199 alone (0.862,95%CI was 0.748-0.975).There was a high improvement in diagnostic sensitivity and accuracy when miR-210 and miR-25 were combind with CA19-9, respectively.Conclusions Plasma miR-21, miR-155, miR-25, miR-210 have diagnostic value for pancreatic cancer , and deserve further study .

Objective The aim of this study was to identify six miRNAs expressed in plasma of patients with pancreatic cancer ( PCa ) and analyze their value as a diagnostic index of pancreatic cancer . Methods Plasma total RNAs were extracted from 30 PCa patients and 26 normal controls, and the abundance of six microRNAs was measured using real-time PCR.The possibility to combine them with CA19-9 as diagnostic biomarkers was analyzed .Results The expression level of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a in plasma of patients with pancreatic cancer were 1.65 ×106 , 5.98 × 104, 2.83 ×103, 3.47 ×106, 2.76 ×106, and 1.03 ×103 (copies/μl), while the normal controls were 4.08 ×105, 2.54 ×104, 8.55 ×102, 1.79 ×106, 9.32 ×105, and 4.67 ×102(copies/μl), respectively, with a significant difference between the two groups (P<0.05).The areas under the ROC curve of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a were 0.893, 0.810, 0.820, 0.766, 0.816 and 0.729, respectively.MiR-21 had the highest diagnostic value when it was used as diagnostic marker alone . The combination of miR-155 and miR-25 was more effective to distinguish PCa from normal than to be used alone, and the area under the ROC curve was 0.913(95%CI 0.838-0.988).When CA199 associated with miR-210 and miR-25, respectively, the areas under the ROC curves were 0.96 (95%CI was 0-1.0) and 0.942(95% CI was 0.876-1.0), which were higher than CA199 alone (0.862,95%CI was 0.748-0.975).There was a high improvement in diagnostic sensitivity and accuracy when miR-210 and miR-25 were combind with CA19-9, respectively.Conclusions Plasma miR-21, miR-155, miR-25, miR-210 have diagnostic value for pancreatic cancer , and deserve further study .

OBJECTIVE: To observe the efficacy of modified acupotome combined with blocking therapy in patients with carpal tunnel syndrome (CTS). METHODS: Fifty-five patients with CTS were divided into three groups, which were modified acupotome group including 26 CTS patients with 28 lesions treated by modified acupotome combined with blocking therapy, traditional acupotome group including 14 CTS patients with 16 lesions treated by traditional acupotome combined with blocking therapy, and blocking therapy group including 15 CTS patients with 15 lesions only treated by local blocking. The treatment outcome and one-year recurrence rate were observed. RESULTS: The response rate and one-year recurrence rate after operation in the modified acupotome group were 85.7% (24/28) and 20.8% (5/24) respectively, which had no significant differences as compared with 81.3% (13/16) and 38.5% (5/13) in the traditional acupotome group. The response rate and one-year recurrence rate after operation in the above two groups were both improved significantly as compared with those in the blocking therapy group which were 46.7% (7/15) and 85.7% (6/7) respectively. There were no acupotome-related adverse effects and injuries observed in the modified acupotome group. CONCLUSION: The modified acupotome is a considerable treatment method for CTS with respect to its simple manipulation and high effectiveness.