Objective:To establish a nomogram model for predicting the hyper-progression recurrence after hepatectomy in patients with hepatocellular carcinoma (HCC) based on circulating tumor cells (CTC).Methods:Clinical data of 231 HCC patients undergoing hepatectomy at the Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital from January 2013 to December 2022 were retrospectively analyzed, including 200 males and 31 females, aged 46(39, 52) years old. Patients were divided into two groups: the modeling group ( n=154) and the validation group ( n=77). According to the state of postoperative hyper-progression recurrence, patients in the modeling group were subdivided into hyper-progression recurrence ( n=39) and non-hyper-progression recurrence group ( n=115). Patients in the validation group were also subdivided into hyper-progression recurrence ( n=16) and non-hyper-progression recurrence group ( n=61). Clinicopathological data such as the total CTC count, alpha-fetoprotein, and postoperative pathology were collected. Logistic regression analysis was used to analyze the influencing factors of postoperative hyper-progression recurrence. A nomogram model was established based on the results of multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to validate the nomogram model. Results:Multivariate logistic regression analysis showed that HCC patients with age ≤45 years old ( OR=6.704, 95% CI: 1.619-27.760, P=0.009), incomplete tumor capsule ( OR=13.292, 95% CI: 3.084-57.295, P=0.001), high total numbers of CTC ( OR=1.101, 95% CI: 1.023-1.186, P=0.011) and high Ki67 index ( OR=52.659, 95% CI: 3.215-862.604, P=0.005) had a high risk of hyper-progression recurrence after hepatectomy. The above three preoperative variables were integrated to construct a nomogram model. The calibration curve showed that the predicted results of the nomogram model were in good agreement with the actual results. The ROC curves of the nomogram model for predicting hyper-progression recurrence after hepatectomy in HCC patients were plotted, and the area under the curve was 0.907 (95% CI: 0.856-0.959) and 0.833 (95% CI: 0.721-0.945) in the modeling group and validation group, respectively. DCA showed that the nomogram model could be used as a valuable predictive tool for the hyper-progression recurrence after hepatectomy. The CIC showed that the population judged by the nomogram model was highly matched with the actual population with hyper-progression recurrence. Conclusions:This study established a nomogram model based on age, tumor capsular integrity and total CTC count, which could accurately predict the postoperative hyper-progression recurrence in HCC patients before hepatectomy. The model is promising in guiding clinical practice after further validation.

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

Objective: To compare the clinical effects of endoscopic thyroidectomy using a modified gasless transsubclavian approach and the traditional neck approach for unilateral papillary thyroid carcinoma (cN0). Methods: The clinical data of 135 patients with cN0 papillary thyroid carcinoma who underwent unilateral thyroidectomy in the Department of Thyroid Surgery, the First Hospital of Jilin University from October 2020 to November 2022 were retrospectively analyzed. There were 37 males and 98 females, aging (43.2±8.8) years (range: 21 to 59 years). There were 51 cases using the modified gasless transsubclavian approach (TS group) and 84 cases using the traditional neck approach (TN group). Comparative analyses were performed between the operative results of the 2 groups by t-test, Wilcoxon rank sum test, and χ² test. Results: All endoscopic operations were successfully completed without conversion to the traditional neck approach. Compared to the TN group, the TS group had a longer operation time (M(IQR)) (73.5 (22.5) minutes vs. 90.0 (30.0) minutes, Z=-5.831, P<0.01), more postoperative drainage (60 (25) ml vs. 95 (45) ml, Z=-6.275, P<0.01), higher hospitalization costs (22 687 (3 488) yuan vs. 26 652 (2 431) yuan, Z=-6.944, P<0.01), and a higher rate of parathyroid autotransplantation (15.5% (13/84) vs. 60.8% (31/51), χ²=29.651, P<0.01). There was no significant difference in the total exposure rate of the central compartment, postoperative hospitalization time, the number of dissected lymph nodes, the number of metastatic lymph nodes, C-reactive protein ratio before and after operation, and preoperative and postoperative parathyroid hormone (all P>0.05). Conclusions: Endoscopic thyroidectomy using the modified gasless transsubclavian approach is safe for cN0 papillary thyroid carcinoma, with longer operating time, more postoperative drainage, higher hospitalization costs, and moredifficulty in preserving the inferior parathyroid gland in situ compared to traditional open surgery.

ObjectiveTo observe the effects of modified Shenqiwan on renal function and fibrosis in diabetic nephropathy mice and explore the underlying mechanism based on the glycogen synthase kinase-3β （GSK-3β）/cyclic adenosine monophosphate （cAMP） response element-binding protein （CREB） signaling pathway. MethodFifty male db/db mice and 10 db/m mice were used in this study. The fifty db/db mice were randomly divided into model group， irbesartan group， and low-， medium-， and high-dose modified Shenqiwan groups. The 10 db/m mice were assigned to the normal group. The mice in the low-， medium-， and high-dose modified Shenqiwan groups were administered with modified Shenqiwan in the dosage form of suspension of Chinese medicinal granules by gavage， those in the irbesartan group were given irbesartan suspension by gavage， and those in the normal and model groups were given distilled water of equal volume by gavage. The intervention lasted for 12 weeks. The blood glucose levels， urine albumin-to-creatinine ratio （UACR）， and the protein expression levels of GSK-3β， CREB， transforming growth factor-β₁ （TGF-β₁）， E-cadherin， Vimentin， fibronectin （FN）， plasminogen activator inhibitor-1 （PAI-1）， and Collagen type Ⅳ （Coll Ⅳ） in the mouse kidneys were recorded before and after treatment. The extent of renal pathological damage was also observed. ResultCompared with the normal group， the model group showed significant increases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β₁， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， decreased protein expression level of CREB （P<0.05）， and severe renal pathological damage. Compared with the model group， the low-， medium-， and high-dose modified Shenqiwan groups and the irbesartan group showed varying degrees of decreases in blood glucose levels， UACR levels， and the protein expression levels of GSK-3β， TGF-β₁， E-cadherin， Vimentin， FN， PAI-1， and Coll Ⅳ in the kidneys （P<0.05）， increased expression level of CREB protein （P<0.05）， and improved renal pathological damage. ConclusionModified Shenqiwan can effectively reduce blood glucose levels， improve renal function， and alleviate fibrosis， and the mechanism of action is related to the inhibition of the GSK-3β/CREB signaling pathway.

Objective:To propose a model using the maximum intensity projection (MIP) of lung field computed tomography (CT) images and deep convolution neural network (CNN) and explore its value in identifying chronic obstructive pulmonary disease (COPD).Methods:A total of 201 subjects were selected from the Second Hospital of Dalian Medical University from January 2010 to May 2021. All subjects were included according to the inclusion criteria and were divided into COPD group (101 cases) and healthy controls group (100 cases). Each patient underwent a high-resolution CT scan of the chest and pulmonary function test. First, the lung field was extracted from CT images and the intrapulmonary MIP images were acquired. Second, with these MIP images as input, the model for identifying COPD was constructed based on a modified residual network (ResNet). Finally, the influence of the number of residual blocks on the performance of the models was investigated. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the identification efficiency.Results:The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of ResNet26 was 76.1%, 76.2%, 76.0%, 76.2%, and 76.0%, respectively; and the AUC of the test was 0.855 (95% CI: 0.799-0.901). The accuracy, sensitivity, specificity, PPV, NPV of ResNet50 was 77.6%, 76.2%, 79.0%, 78.6%, and 76.7%, respectively; and the AUC of the test was 0.854 (95% CI: 0.797-0.900). The accuracy, sensitivity, specificity, PPV, NPV of ResNet26d was 82.1%, 83.2%, 81.0%, 81.6%, and 82.7%, respectively; and the AUC of the test was 0.885 (95% CI: 0.830-0.926). Conclusions:The COPD identification model via MIP images from CT images within the lung and deep CNN is successfully constructed and achieves accurate COPD identification. And it can provide an effective tool for COPD screening.

Objective To observe the effect of ulinastatin on tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in radiation-induced lung injury.Methods Severity-two female SD rats were randomly divided into 3 groups as control group,irradiation group and treatment group(administered with Ulinastatin).Rats in irradiation group and treatment group were irradiated with linear accelerator at a single dose of 25 Gy.After irradiation rats in treatment group were injected daily with ulinastatin at a dose of 100000 U-kg-1·d-1 for 7 days through caudal vein while rats in control group and irradiation group were injected with the same volume of saline.Rats were killed at 2 h,4,8 and 24 weeks.Samples of lung tissues were observed by using HE staining.Expression of TNF-α in lung was determined by Western blot and expression of IL-6 in serum was determined by ELISA.Data were analyzed by SPSS software.Results Expressions of TNF-α in lung and IL-6 in serum increased significantly after irradiated in irradiation group compared with control group,and it reached the peak at 4 weeks(q=5.63、6.21,P＜0.01).Though expressions of TNF-α and IL-6 in ffeatment group also increased compared with control group,the difference between irradiation group and treatment group was statistic significantly(q=4.97、7.42,P＜0.01).Conclusions TNF-α and IL-6 play an important role in radiation-induced lung injury.Ulinastatin could suppress the inflammatory response and radiation-induced lung injury effectively by decreasing the levels of TNF-α and IL-6.

BACKGROUND: The pathological characteristics of pulmonary interstitial fibrosis are the proliferation of a large number of fibroblasts and the increasing deposition of matrix collagen that takes the place of normal lung structure. Fluvastatin can inhibit the proliferation of fibroblasts and many other cells.OBJECTIVE: To investigate the effects of fluvastatin in inhibiting the proliferation of rat lung fibroblasts cultured in vitro and its influence on bleomycin-induced pulmonary fibrosis and ventilation function.DESIGN: A randomized controlled trial.SETTING: Department of Respiratory Diseases, Xijing Hospital, Fourth Military Medical University of Chinese PLA; Teaching and Research Section of Pathology, Department of Basic Medicine, Fourth Military Medical University of Chinese PLA; Research Institute ofOrthopedics, Xijing Hospital,Fourth Military Medical University of Chinese PLA.PARTICIPANTS: The study was conducted in the laboratory of Department of Respiratory Diseases, Xijing Hospital of Fourth Military Medical University of Chinese PLA from January to December 2001. Thirty-one healthy adult male Sprague-Dawley(SD) rats of grade Ⅰ were selected in this study.INTERVENTIONS: The fibroblasts derived from the lung normal of one rat were cultured in vitro in media containing fluvastatin. The effect of fluvastatin on the growth curve and the effect of its different concentrations(0, 1 × 10-7,1 ×10-6, 1 ×10-5, 1 ×10-4, 1 ×10 3and 1 ×10-2 mol/L, fluvastatin of 0 mol/L was taken as the blank control group) in inhibiting the cultured cells were observed with MTT colorimetry. The effect of fluvastatin on the division index of the fibroblasts was analyzed by direct cell counting Hydroxyproline colorimetry was used to detect the influence of fluvastatin on the collagen secretion in the media. The other 30 SD rats were divided into six groups: normal control group, bleomycin-induced group and fluvastatin-treated groups(TH 1,TE1, TH15 and TL15 groups) named according to the date of giving fluvastatin,i. e. the 1st day and the 15th day, after the rats were given bleomycin A5. All the rats were killed 28 days later. The number of fibroblasts, the thickness of alveolar wall and the area of mesenchyma in lung tissue were measured by HE staining. The extracellular matrix and collagen in lung tissue were observed by Masson and sirius red staining, and hydroxyproline in lung tissue homogenates was measured.MAIN OUTCOME MEASURES: Fibroblast growth curve and division index of rat lung, hydroxyproline in the media and lung tissue homogenates,number of fibroblasts and the thickness of alveolar wall, the area of mesenchyma, extracellular matrix and collagen contents in lung tissue.RESULTS: Fluvastatin could inhibit the proliferation of the rat lung fibroblasts cultured in vitro(t=4.20 to 17.52, P < 0.01), and its inhibitory effect was increased with the increased dose of fluvastatin, which showed a dose-dependent effect. The 1 × 10-4 mol/L fluvastatin could completely inhibit the proliferation of the cultured cells, and the A490 value from the 2nd day on the fibroblasts by MTT colorimetry was not insignificantly different from those on the 1st day( P > 0.05) . The division index of the fibroblasts and secretion of collagen were obviously decreased by fluvastatin( t = 8. 037,P <0.01; t =3.99 to 10. 84, P <0.05 or P <0.01). In vivo, the number of fibroblasts, the thickness of lung alveolar wall, the area of mesenchyma and the content of hydroxyproline in lung tissue were significantly higher in bleomycin group than in control group( t =4. 62 to 11.93, P < 0. 01), while those in the fluvastatin-treated groups were lower than those in bleomycin group in different degrees( t = 2.69 to 7.65, P < 0.05 to 0.01 ) . The distribution of extracellular matrix and types Ⅰ and Ⅲ collagen in lung tissue were obviously increased in bleomycin group as compared with that in control group, but decreased in different degrees in fluvastatin-treated groups.CONCLUSION: Fluvastatin can significantly inhibit the proliferation of rat lung fibroblasts in vitro, suggesting that it may be an effective drug for pulmonary fibrosis. Treatment at earlier stage is more effective than at advanced stage.

BACKGROUNDRecent researches discovered that artemisinin and its derivatives had anti-tumor activity. Dihydroartemisinin is one of the derivatives with higher activity. This study is to explore the effect of dihydroartemisinin on the proliferation of human lung adenocarcinoma cell line A549, so as to provide experimental base for treatment of lung cancer.

METHODSInhibition of proliferation in vitro was measured by MTT assay. The cell growth curve was drawn according to cell counts. The population doubling time was counted in logarithmic growth phase, DNA contents were measured by flow cytometry. Cell cycles were observed at the same time after the treatment. And the nude mice bearing A549 cancer cells were applied to detect the effect of dihydroartemisinin in vivo.

RESULTSDihydroartemisinin inhibited A549 cell proliferation in a concentration-dependent manner, after 96h of treatment, the IC50 for dihydroartemisinin inhibition of cell number was 0.23μmol/l. The population doubling time for human lung adenocarcinma in the control group was 21.3h and that in the dihydroartemisinin group was 38.5h . An highly significant difference was observed between the two groups (P < 0.01). Cells in G0 plus G1 were increased after the dihydroartemisinin treatment. The tumor inhibiting rate of dihydroartemisinin was 54.3% in vivo.

CONCLUSIONSDihydroartemisinin has marked anticancer activity on human lung adenocarcinoma cell line A549 both in vitro and in vivo. The inhibition in vitro is related to blockade of G0 and G1 phases.

BACKGROUNDTo evaluate the effect of combination chemotherapy with etoposide plus ifosfamide and cisplatin (VIP) for small cell lung cancer (SCLC).

METHODSOne-hundred and twenty patients with localized SCLC who never received chemotherapy were randomly divided into VIP regimen group and EP regimen group. The response and toxicity were evaluated after 3 cycle chemotherapy with VIP or EP respectively. In addition, salvage chemotherapy by VIP was given to 25 patients, who had progression or recurrence of the cancer after treatment with EP regimen, and the response was assessed after 3 cycles of the treatment.

RESULTSIn 118 evaluable patients, response rate was 89.6% for VIP regimen group and 78.3% for EP regimen group. There was no remarkable difference of response rates between the two groups. Toxicity of the two regimens was similar. However, complete response rate for VIP regimen group (43.1%) was significantly higher than that for EP regimen group (25.0%) (P < 0.05). In 23 patients who were progressive or relapsed after treatment with EP regimen, the complete response, partial response, progression and total response were 13.0%, 39.1%, 47.8% and 52.2% respectively.

CONCLUSIONSVIP regimen may be used as the first-line chemotherapy for localized SCLC, its efficacy is superior to that of EP regimen. VIP can also be used as salvage chemotherapy regimen for patients with SCLC who failed to EP regimen chemotherapy.

BACKGROUNDTo observe and explore the effects and mechanisms of fibronectin (FN) on invasion of different types of lung cancers.

METHODSUsing tumor invasion models in vitro of plates coated with FN and Boyden chambers with FN filter, differences of adhesion and migration between small cell lung cancer cell line (054A) and adenocarcinoma cell line (A549) were investigated, and proliferative effects of FN on cells were examined. In the meantime the invasive capability changes were observed after cell suspensions were preincubated with anti-α5, anti-α3 and anti-β1 integrin antibodies, respectively.

RESULTSFN could improve the adhesion, migration and proliferation of A549 more markedly than that of 054A. The number of adhesive cells in A549 cell line changed from 34.7± 5.1 to 189.4±12.3 with time from 2h to 12h compared with that from 19.8±7.9 to 159.2±11.9 in 054A cell line (P < 0.05 or P < 0.01). A549 cell line had 142.7±5.9 migration cells while 054A cell line had 89.4±4.7 (P < 0.01). FN could improved the proliferation in A549 cell line from 0.250±0.019 to 0.754±0.025 (P < 0.01) in concentration-dependent way, but in 054A from 0.205±0.026 to 0.286±0.029. And these effects were mediated mainly by α3β1 and α5β1 receptors in A549, but α3β1 in 054A.

CONCLUSIONSLung cancers with different origins express so different types and extents of integrin receptors that effects of FN on tumors are various, which is one of important reasons of different invasive capability of lung cancers.