Optimal fibular tunnel direction for anterior talofibular ligament reconstruction: 45 degrees outperforms 30 and 60 degrees.

PURPOSE: There is currently no consensus on the optimal drilling direction of the fibular bone tunnel for anterior talofibular ligament (ATFL) reconstruction, and few studies have investigated the potential injury to the peroneus longus and brevis tendons and the possibility of fibular fractures during the drilling process. The aim of this study was to assess the potential risk of drilling the tunnel from different directions and determine the most appropriate tunnel direction. The hypothesis was that drilling the tunnel in the 45-degree direction would be the safest and most suitable for the fibular tunnel. METHODS: Forty-eight fibular tunnels were drilled on fresh ankle specimens using a K-wire guide and a 5.0 mm hollow drill. Three tunnel orientations were created, parallel to the sagittal plane of the long axis of the fibula and angled 30°, 45°, and 60° to the coronal plane. The length of the fibular tunnel and the distances from the outlet of the K-wire to the peroneus longus and brevis tendons were measured. The occurrence of a fibula fracture was also observed. RESULTS: The lengths of the bone tunnels in the three groups were 32.9 ± 6.1 mm (30°), 27.2 ± 4.4 mm (45°) and 23.6 ± 4.0 mm (60°). The length of the tunnel drilled at 30° was the longest when compared with that of the tunnels drilled at 45° and 60° (all p values < 0.05). The distances from the outlet of the K-wire to the peroneus longus tendon were 3.0 ± 3.8 mm (30°), 3.8 ± 3.2 mm (45°) and 5.3 ± 1.8 mm (60°), and the distances to the peroneus brevis tendon were 4.2 ± 4.0 mm (30°), 6.1 ± 3.8 mm (45°), 7.9 ± 3.5 mm (60°). In terms of protecting the peroneus longus and brevis tendons, drilling in the 60° direction was better than drilling in the 30° and 45° directions (all p values < 0.05). The risk of injury to the peroneal longus and brevis tendons was 62.5% (30°), 31.3% (45°), and 0% (60°). Although no fibular fractures were observed in any of the three directions, drilling the bone tunnel in the 60° direction disrupted the lateral cortex of the fibula. CONCLUSION: This study shows that drilling the tunnel in the 45° direction is less likely to cause injury to the peroneus longus and brevis tendons, while ensuring that the tunnel has a sufficient length and avoiding fracturing the distal fibula. Drilling a fibular bone tunnel in a 45° direction is safer and recommended for ATFL reconstruction.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes.

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

[Safety Analysis of Perioperative Period in Non-Small Cell Lung Cancer Patients with Comorbid Pneumoconiosis].

Objective: To explore the surgical safety of patients with comorbid non-small cell lung cancer (NSCLC) and pneumoconiosis. Methods: In this study, the clinical data of 165 NSCLC patients treated at West China Fourth Hospital, Sichuan University from August 2019 to May 2021 were collected. Among them, 21 patients with comorbid pneumoconiosis were included in the pneumoconiosis group, and the remaining 144 patients were included in the general group. Radical resection for lung cancer was performed in both groups. The perioperative clinical data, including preoperative, intraoperative and postoperative indicators, of the two groups were compared and analyzed. Results: There was no perioperative death in either group. The proportions of male patients and patients with smoking history in the pneumoconiosis group were significantly higher than those in the general group ( P<0.05). The body mass index (BMI), pulmonary ventilation function and diffusion function in the pneumoconiosis group were significantly lower than those in the general group ( P<0.05). There was no significant difference in the median operative time and the median volume of intraoperative blood loss between the pneumoconiosis group and the general group. In the pneumoconiosis group, the proportion of advanced tumors (stage Ⅱ/Ⅲ), incidence of postoperative complications, median duration of postoperative intubation, and postoperative length of hospital stay were higher/longer than those of the normal group ( P<0.05). Compared with the general group, the incidences of lymph node calcification, dense pleural adhesion and surgical method alteration (switching from thoracoscopic surgery to open surgery or video-assisted thoracoscopy) were also significantly higher in the pneumoconiosis group ( P<0.05). Univariate analysis showed that age, smoking history, pneumoconiosis, pulmonary ventilation dysfunction, lymph node calcification, dense pleural adhesion and the volume of intraoperative blood loss were the risk factors for postoperative complications. Further multivariate regression analysis demonstrated that smoking history ( OR=1.37, P<0.05), lymph node calcification ( OR=2.36, P<0.05) and pulmonary ventilation dysfunction ( OR=5.21, P<0.05) were independent risk factors for postoperative complications. Conclusion: NSCLC patients with comorbid pneumoconiosis face relatively greater risks during the perioperative period when they undergo radical resection for lung cancer. Therefore, the close attention of surgeons and the nursing staff should be raised accordingly.

Characterization of the immune cell infiltration landscape in lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have played an important role in the treatment of lung adenocarcinoma (LUAD). However, their effectiveness is limited, and many patients exhibit a weak response. In this study, we propose a new and more effective immunophenotyping method for evaluating the prognosis and tumor microenvironment (TME) cellular infiltration characteristics in LUAD patients and their response to immunotherapy. Based on the transcriptomic and prognostic data of 584 patients with LUAD collected from TCGA cohort and GEO dataset, we combined tumor immune infiltration, the TME, and immune-related genes to score each sample using principal component analysis (PCA) and divided the patients into two subgroups with high and low tumor immune infiltration (TII) scores. The high-TII score group was characterized by increased immune activation and apoptosis signaling pathways. Moreover, clinical subgroup analysis demonstrated that the TII immune score was also applicable to different clinical groups and the high-TII score group still exhibited good prognosis and better response to ICIs. This study mapped the TII landscape in LUAD patients and confirmed that the TII score is helpful for predicting patient response to immunotherapy and may guide more effective immunotherapeutic strategies.

H-Plasty Repair Technique Improved Tibiofemoral Contact Mechanics After Repair for Adjacent Radial Tears of Posterior Lateral Meniscus Root: A Biomechanical Study.

PURPOSE: To compare the time-zero tibiofemoral contact mechanics among the 4 different suturing repairs: transtibial pullout suture repair, suture anchor repair, side-to-side repair, and H-plasty repair. METHODS: Twenty-four human cadaveric knees were included. Each lateral meniscus condition (intact, radial tear, and repair) was tested under a 1000-N axial compressive load at 0°, 30°, 60°, and 90° of flexion. Four different repair techniques, transtibial pullout, suture anchor, side-to-side, and H-plasty repair technique, were tested. Tibiofemoral mean and peak contact pressure and contact area in the lateral and medial compartments were measured by Tekscan sensors. RESULTS: Radial tears adjacent to the posterior lateral meniscus root produced significantly decreased contact area and increased mean and peak contact pressures in the lateral compartment across all angles (P < .05). All repair groups could improve the contact mechanics relative to the torn condition (P < .05), but only H-plasty repair showed no significant difference in the mean and peak contact pressure and contact area compared with that of the intact state at all flexion angles (P > .05). CONCLUSIONS: The results showed that the tibiofemoral contact mechanics after adjacent radial tears of the posterior lateral meniscal root were improved to the intact level by H-plasty repair at time-zero. The additional vertical mattress sutures act as "stabilizers" to provide a more stable environment in distributing vertical tibiofemoral pressure. The other 3 repair techniques also significantly improved lateral tibiofemoral contact mechanics relative to the corresponding tear conditions. CLINICAL RELEVANCE: The results of this study suggest that H-plasty repair can restore the biomechanical properties to the intact state. Since it was a time-zero cadaveric study, the results should be carefully used in clinical practices.

Tibiofemoral Contact Mechanics After Horizontal or Ripstop Suture in Inside-Out and Transtibial Repair for Meniscus Radial Tears in a Porcine Model.

PURPOSE: To compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees in each group. METHODS: Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent 4 testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments. RESULTS: All repair groups improved their contact mechanics when compared with the tear state among all flexion angles analyzed (all P < .05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles, whereas the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P > .05). CONCLUSIONS: Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles. CLINICAL RELEVANCE: Our results suggest that both inside-out and transtibial ripstop repairs for radial tears can restore tibiofemoral contact mechanics to the intact state. Since the study were performed in an open fashion porcine model, the results should be carefully used in clinical practices, and the efficacy of the techniques through arthroscopic method should be further explored.

All-Inside Arthroscopic Modified Broström Technique to Repair Anterior Talofibular Ligament Provides a Similar Outcome Compared With Open Broström-Gould Procedure.

PURPOSE: To introduce an all-inside modified Broström technique to suture the anterior talofibular ligament (ATFL) and inferior extensor retinaculum (IER) under arthroscopy and to compare its outcomes with those of the conventional open procedure. METHODS: All patients who underwent arthroscopic or open repair of the ATFL between June 2014 and December 2017 were included in this study. Visual analog scale (VAS), Karlsson and Peterson (K-P), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot, and Tegner activity scores, as well as manual anterior drawer test (ADT), were used to evaluate the patients preoperatively and ≥2 years after surgery. The Sefton grading system was used to assess the level of satisfaction after surgery. Detailed surgical data and intraoperative findings were documented at the time of surgery. RESULTS: A total of 67 patients, 31 in the arthroscopic group and 36 in the open group, were included in this study (43 men and 24 women, mean body mass index 24.00, range 19.53 to 30.03). The surgical duration in the arthroscopic group (median, 34 minutes; range, 25 to 74) was significantly shorter than that in the open group (mean, 43.08 ± 8.11 minutes; 95% confidence interval [CI] 40.34 to 45.83) (P = .007). At the last follow-up, the subjective functional scores and ADT results improved significantly in both cohorts (P < .001). However, no significant difference was found in the VAS score (1.74 ± 1.24, 95% CI 1.29 to 2.2, in the open group versus 1.58 ± 1.2, 95% CI 1.18 to 1.99, in the arthroscopic group; P = .581), AOFAS score (91.71 ± 5.46, 95% CI 89.71 to 93.71, versus 90.67 ± 5.59, 95% CI 88.78 to 92.56; P = .444), K-P score (87.52 ± 7.59, 95% CI 84.73 to 90.3, versus 88.75 ± 5.56, 95% CI 86.87 to 90.63; P = .446), and ADT evaluation (normal: 96.77% versus 94.44%, P = .557) between the arthroscopic and open groups, respectively. In addition, 28 cases (90.32%) in the arthroscopic group and 32 (88.89%) in the open group achieved satisfactory results based on the Sefton grading system (P = .736). Seventeen patients (47.2%) in the open group and 18 patients (58.1%) in the arthroscopic group underwent Tegner evaluation after surgery, which showed no significant difference (5, interquartile range [IQR] 1 in the open group versus 5, IQR 3 in the arthroscopic group; P = .883). Complications were reported in 4 (11.1%) and 2 (6.5%) patients who underwent open and arthroscopic surgeries, respectively (P = .813). CONCLUSIONS: Both open and arthroscopic modified Broström surgeries generated favorable outcomes, with a significant improvement compared with the preoperative condition. Compared with the open Broström-Gould procedure, the all-inside arthroscopic modified Broström technique produced equivalent functional and clinical results at a minimum of 2 years after the operation, with a shorter surgical duration. Arthroscopic repair might be a safe and viable alternative to open surgery for lateral ankle stabilization. LEVEL OF EVIDENCE: III.

A novel surgical technique for arthroscopic repair of type II posterior lateral meniscal root tear.

BACKGROUND: Several suture repair techniques have been reported for radial tear close to the posterior lateral meniscal root (type II PLMRT). However, no study has evaluated the clinical results after repair using the FasT-Fix system. This paper describes a novel H-plasty surgical repair technique and reports its clinical results. METHODS: From January 2015 to January 2017, 47 patients underwent repair of type II PLMRT with concomitant anterior cruciate ligament reconstruction and were included in this study. Assessments performed preoperatively and at final follow-up included the Lysholm score, subjective International Knee Documentation Committee (IKDC) score, and knee stability assessments (pivot-shift test, Lachman test, KNEELAX arthrometer side-to-side difference). Magnetic resonance imaging was used to compare the lateral meniscal extrusion pre- versus postoperatively. Second-look arthroscopy was performed to evaluate the meniscal healing in 38 cases. RESULTS: Forty-seven patients were followed up for an average of 30.7 months (range 18-46 months). No patients experienced meniscal mechanical symptoms. At final follow-up, there were significant improvements in the Lysholm score, IKDC score, knee stability assessments, and lateral meniscal extrusion compared with the preoperative values. In the 38 of 47 patients that underwent second-look arthroscopy after an average of 17.5 months (range 14-19 months), all repairs (100%) were completely healed. CONCLUSIONS: The novel H-plasty repair using the FasT-Fix system was an effective surgical treatment for type II PLMRT. Considering the satisfactory clinical results and the convenience of the surgery, H-plasty repair is recommended to be used preferentially.

Predictive value of pancreatic dose-volume metrics on sarcopenia rate in gastric cancer patients treated with adjuvant chemoradiotherapy.

OBJECTIVE: To evaluate the relationship of sarcopenia with the pancreatic dose-volume histogram (DVH) in gastric cancer patients treated with adjuvant chemoradiotherapy (CRT) after radical gastrectomy. METHODS: A retrospective study was performed on the data in Zhongnan Hospital of Wuhan University from January 2008 to December 2016. Skeletal muscle index (SMI) was analyzed by cross-sectional areas of body composition at the level of third lumbar (L3) vertebrae, which was measured using single-slice computer tomograph (CT) prior to CRT, at 6 months and 12 months after CRT respectively. Logistic regression analysis was conducted to explore the potential clinical risk factors of sarcopenia in this patients cohort. Regarding the dosimetrics of pancreas, the sarcopenia rate was compared between the two groups divided according to the cut-off value determined by the receiver operating characteristic (ROC) curves. RESULTS: One hundred and fifty-three gastric cancer patients were eligible in this study. The median postoperative follow-up was 36 (7-115) months. The mean dose of pancreas was 4399.7 ± 396.0 cGy. The incidence of sarcopenia prior to CRT, at 6 months and 12 months later were 29.4% (45/153), 27.3% (35/128) and 37.0% (37/100). Both sarcopenia at 6 months (HR = 2.038, 95%CI = 1.084-3.833, P = 0.027) and sarcopenia at 12 months (HR = 2.216, 95%CI = 1.007-4.873, P = 0.048) were the independent prognostic factor of gastric cancer patients. V46 remained to be the only independent risk factor of sarcopenia at 6 months (OR = 3.889, 95%CI = 1.099-13.764, P = 0.035) and 12 months (OR = 6.067, 95%CI = 1.687-21.821, P = 0.006) in multivariate logistic regression analysis. Among the dosimetric parameters used for ROC analysis, the V46 showed the highest area under the curve (AUC = 0.707). Here is the relationship between sarcopenia rate and the cut-off value for V46. Higher sarcopenia rate at 6 months was noted in 42.6% patients with V46 ≥ 57% compared with 9% of patients with V46 < 57% (P < 0.001). The sarcopneia rate at 12 months was 52% with V46 ≥ 57% and 25% with V46 < 57% (P = 0.010). CONCLUSION: Gastric cancer with sarcopenia after adjuvant CRT had poorer survival. Higher dose and larger irradiated volume of pancreas correlated with higher risk of sarcopenia. Appropriated administration of pancreas dose-volume may be conducive to reduce the risk of sarcopenia and improve survival in gastric cancer patients treated with adjuvant CRT.

Mitochondrial DNA content reduction induces aerobic glycolysis and reversible resistance to drug-induced apoptosis in SW480 colorectal cancer cells.

Mutations and reductions in mitochondrial DNA (mtDNA), which are frequent in human tumors, may contribute to enhancing their malignant phenotypes. However, the effects of mtDNA abnormalities in colorectal cancer remain largely unknown. In this study, mtDNA-reduced cell model was established by partial depletion of mtDNA in SW480 cells and the effects of mtDNA reduction in colorectal cancer cells were investigated. We found that mtDNA-reduced cells had enhanced glucose uptake and generated markedly higher level of lactate. These changes were accompanied by only a slight reduction in ATP production compared with the parent cells. Furthermore, the activity of the glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), was increased in mtDNA-reduced cells. These results suggested a switch to aerobic glycolysis in mtDNA-reduced cells, which helped the cells to gain a survival advantage. Notably, when mtDNA content was restored, metabolism returned to normal. In addition, the mtDNA-reduced cells were highly resistant to 5-fluorouracil- and oxaliplatin-induced apoptosis and this drug resistance was reversible following recovery of the mtDNA content. We also found that the Akt/mTOR pathway was activated in the mtDNA-reduced cells. This pathway might play a significant role in drug resistance in the mtDNA-reduced cells as drug susceptibility was restored when this pathway was inhibited. Taken together, our results supported the notion that mtDNA reduction induced aerobic glycolysis and a reversible apoptosis-resistant phenotype in SW480 cells, and that the Akt/mTOR pathway might be involved in the drugs-induced apoptosis resistance.

Meniscal Ramp Lesion Repair Using the FasT-Fix Technique: Evaluating Healing and Patient Outcomes with Second-Look Arthroscopy.

Although the suture-hook technique remains popular for meniscal ramp lesions, which frequently occur after anterior cruciate ligament (ACL) injury, it is unclear whether the all-inside FasT-Fix technique (Smith & Nephew, Andover, MA) is appropriate for the repair of ramp lesions. This study evaluated results of arthroscopic FasT-Fix meniscal ramp lesion repair using second-look arthroscopy. From August 2010 to December 2014, 46 knees diagnosed with combined ACL injury and ramp lesion underwent ACL reconstruction with meniscal repair using the FasT-Fix technique. We classified ramp lesions into three types according to tear pattern: meniscotibial ligament tear, meniscocapsular tear, and combined meniscotibial/meniscocapsular tear. Second-look arthroscopy was performed postoperatively. The healing capacity of the ramp lesion was evaluated retrospectively. At the final follow-up (mean = 32 months), the Lysholm knee score and the International Knee Documentation Committee (IKDC) objective score were compared with preoperative scores. All patients (n = 46) underwent a second-look arthroscopy, with 45 (97.8%) exhibiting complete or partial healing after the FasT-Fix technique was used in conjunction with ACL reconstruction. The Lysholm knee score and IKDC objective score were significantly better than preoperative scores at final follow-up. The FasT-Fix technique for meniscal ramp lesion repair-when performed with concomitant ACL reconstruction-exhibits excellent healing results.

Log odds of positive lymph nodes is superior to the number- and ratio-based lymph node classification systems for colorectal cancer patients undergoing curative (R0) resection.

The metastatic lymph node status (N classification) is an important prognostic factor for patients with colorectal cancer (CRC). The aim of the present study was to evaluate and compare the prognostic assessment of three different lymph node staging methods, namely standard lymph node (pN) staging, metastatic lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in CRC patients who undergo curative resection (R0). Data were retrospectively collected from 192 patients who had undergone R0 resection. Kaplan-Meier survival curves, Cox proportional hazards model and accuracy of the three methods (pN, LNR and LODDS) were compared to evaluate the prognostic effect. Univariate analysis demonstrated that pN, LNR and LODDS were all significantly correlated with survival (P=0.001, P<0.001 and P<0.001, respectively). The final result of the 3-step multivariate analysis demonstrated that LODDS was superior to the other two N categories. Patients in the same pN or LNR classifications may be classified into different LODDS stages with different prognoses. Thus, LODDS may be a meaningful prognostic indicator and superior to the pN and LNR classifications in CRC patients who undergo curative (R0) resection.

In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni.

AIM: To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl4)-induced liver damage in rats. METHODS: The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-ß-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ß-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAE against CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1 (CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase catalytic subunit (γ-GCSc) protein expression was measured by Western blot. RESULTS: Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation (P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE (160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes (P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression. CONCLUSION: CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies.

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

MicroRNA-320 regulates the radiosensitivity of cervical cancer cells C33AR by targeting ß-catenin.

Cervical cancer is the second most common malignancy in women worldwide and always has recurrence owing to radioresistance. MicroRNA (miRNA or miR) has been identified to relate to the sensitivity of cancer radiotherapy. Here, we investigated the potential of miRNA-320 as a biomarker for radiosensitivity by targeting ß-catenin in cervical cancer. A radioresistant cervical cancer cell line, C33AR, was established, and the radioresistance of C33AR cells was confirmed by a colony-formation assay. The expression of miRNA-320 was detected by reverse transcription-quantitative polymerase chain reaction, and compared between C33A and C33AR. ß-catenin, the target of miRNA-320, was determined at the protein level by western blotting after transfecting the inhibitor of miRNA-320. The expression of miRNA-320 was markedly decreased in C33AR cells, which appeared to be more radioresistant, compared with its parental cell line C33A. Target prediction suggested that miRNA-320 negatively regulated the expression of ß-catenin. Knockdown of ß-catenin increased C33AR radiosensitivity, which revealed that the inhibition of ß-catenin could rescue the miRNA-320-mediated cell radioresistance. On the other hand, overexpressing miRNA-320 increased C33AR radiosensitivity. In conclusion, miRNA-320 regulated the radiosensitivity of C33AR cells by targeting ß-catenin. This finding provides evidence that miRNA-320 may be a potential biomarker of radiosensitivity in cervical cancer.

Extrapleural locating method in computed tomography-guided needle biopsies of 1,106 lung lesions.

Transthoracic needle biopsy is considered to be safe and effective for the diagnosis of focal lung lesions. The aim of the present study was to evaluate factors affecting the accuracy and safety of automated cutting needle lung biopsy (ACNB) using a new extrapleural locating (EPL) method. Computed tomography (CT)-guided needle biopsies were performed on 1,065 patients between March 2005 and May 2012 using the EPL method. The locating needle remained in the chest following extrapleural positioning, while the radiologist confirmed the puncture angle and distance between the locating needle and lesion. The biopsy instrument was advanced into the lung, and the core needle was subsequently fired into the lesion based on the direction indicated by the locating needle. Univariate and multivariate regression analyses were used to evaluate the diagnostic accuracy and safety of the procedure. The sensitivity, specificity, positive predictive value and negative predictive value of the extrapleural method were 91.9, 100, 100 and 82.9%, respectively, and the overall diagnostic accuracy was 94.2%. Significant risk factors affecting accuracy were younger age, atelectasis, hemoptysis and lesion depth (P<0.03). Multivariate logistic regression analysis revealed that the risk of malignant lesions receiving a false-negative diagnosis decreased for each additional year of subject age [odds ratio (OR), 0.97; P=0.027] and increased with each millimeter increase in lesion depth (OR, 1.03; P=0.008). Among the 1,106 lesions biopsied, 207 were associated with pneumothorax, 251 with hemorrhage and 58 with hemoptysis. Multivariate analysis revealed that lesion size and emphysema affected pneumothorax incidence, while age, lesion location and depth and emphysema significantly affected hemorrhage incidence (P<0.05). In conclusion, low-dose, CT-guided ACNB with the EPL method provides a safe and accurate diagnosis.

Expression of various protection of telomeres 1 variants is associated with telomere length and radiosensitivity in colon and gastric adenocarcinoma cells in vitro.

Protection of telomeres 1 (POT1) is a telomere-binding protein, which binds to the single-stranded DNA extensions of telomeres and regulates telomere length. Different POT1 mRNA variants were examined and compared with telomere length and radiosensitivity in colon and gastric adenocarcinoma cells. POT1 production and telomere lengths were assessed using 10 human cancer cell lines by quantitative polymerase chain reaction (qPCR). POT1 mRNA levels, which were relatively stable, were significantly correlated with telomere length in gastric cancer cells and colon cancer cells, except for HT29 (P<0.01). POT1 v5 indexes were closely associated with radiosensitivity in colon cancer cells and gastric cancer cells (P<0.05). In conclusion, POT1 may be a good marker for the examination of cell-specific telomere length and radiosensitivity.

Elevated expression of USP9X correlates with poor prognosis in human non-small cell lung cancer.

BACKGROUND: The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis. METHODS: Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value <0.05 was considered to be significant. RESULTS: The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P<0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P<0.001), clinical stage (P<0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR =2.244, P=0.028). CONCLUSIONS: The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC.