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Our previous study indicated that reactive oxygen species (ROS) are critically involved in chronic pain. Sestrin2 (Sesn2), a novel stress-inducible protein, is evidenced to reduce the generation of ROS. The study examined the role of Sesn2 in osteoarthritis (OA) pain and delineated the underlying molecular mechanisms.In the present study, we investigated the impact of Sesn2 on mitochondrial biogenesis in a rat model of OA pain. After adeno-associated viral (AAV)-Sesn2EGFP was injected for 14 days, OA was induced by intra-articular injection of monosodium iodoacetate (MIA). We assessed pain behaviors (weight-bearing asymmetry and paw withdrawal threshold) and explored possible mechanisms in the L4-6 spinal cord.Our results showed that overexpression of Sesn2 in the spinal cord alleviated pain behaviors in OA rats. Moreover, overexpression of Sesn2 increased the activity of AMP-activated protein kinase (AMPK) signaling and significantly restored mitochondrial biogenesis. Besides, Sesn2 overexpression inhibited the activation of astrocytes and microglia, and decreased the production of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the spinal cord of the OA pain rats. These effects were significantly reversed by an AMPK inhibitor.Collectively, these results suggest that Sesn2 overexpression ameliorates mechanical allodynia and weight-bearing asymmetry in OA rats via activation of AMPK/PGC-1α-mediated mitochondrial biogenesis in the spinal cord. Moreover, Sesn2 overexpression attenuates OA-induced neuroinflammation at least partly by activating AMPK signaling. Sesn2 may become an encouraging therapeutic strategy for OA pain relief and other disorders.

Patients with hepatocellular carcinoma (HCC) bile duct tumor thrombus (BDTT) have a high rate of postoperative recurrence. We aimed to describe the patterns and kinetics of recurrence in BDTT patients and provide management options accordingly.This retrospective study included 311 HCC patients with BDTT who underwent surgery from 2009 to 2017 at five centers in China. The hazard rate of recurrence was calculated using the hazard function.The hazard rate of intrahepatic recurrence was higher than that of extrahepatic recurrence (0.0588 vs. 0.0301), and both showed a decreasing trend, and the intrahepatic recurrence and extrahepatic recurrence risk decreased to a lower level after 40 and 20 months, respectively. Patients who underwent anatomic resection had a consistently lower hazard rate of recurrence than patients who underwent nonanatomic resection, whereas patients who received postoperative adjuvant transarterial chemoembolization (TACE) mainly had a lower hazard rate of recurrence in the first year than patients who did not.The follow-up of BDTT patients should be at least 40 months because of its high rate of recurrence, in parallel with the need for vigilance for extrahepatic recurrence within 20 months. Anatomic hepatectomy and adjuvant TACE are recommended to improve BDTT patient outcomes.

Jia-Yi Wu,1,2,* Zhen-Yu Yin,3,* Yan-Nan Bai,1,2 Yu-Feng Chen,4 Song-Qiang Zhou,1,2 Shuang-Jia Wang,5 Jian-Yin Zhou,6 Yi-Nan Li,2 Fu-Nan Qiu,1,2 Bin Li,5 Mao-Lin Yan1,2 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Hepatobiliary Surgery, Xiamen Traditional Chinese Medical Hospital, Xiamen, Fujian Province, 361000, People’s Republic of China; 4Department of Hepatobiliary Surgery, The Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, 363000, People’s Republic of China; 5Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, 361000, People’s Republic of China; 6Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Lin Yan; Bin Li Tel +86 0591-88217130; +86 13606056652Fax +86 0591-87557768; +86 0592-2132222Email yanmaolin74@163.com; wasalee@126.comBackground: Lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) exerted promising effects on unresectable hepatocellular carcinoma (uHCC). We assessed the safety and clinical efficacy of triple therapy [LEN+PD-1+transcatheter arterial chemoembolization (TACE)] in uHCC.Methods: uHCC patients with an ECOG PS score of 0– 1 and Child–Pugh class A who underwent triple therapy were included. The primary endpoint was objective response rate (ORR) based on mRECIST. Secondary endpoints were conversion rate to liver resection and treatment-related adverse events.Results: Between November 2018 and December 2020, 62 uHCC patients who underwent triple therapy at four major cancer centers in China were analyzed, including 35 in BCLC-C, 21 in BCLC-B, and 6 in BCLC-A. With a median follow-up of 12.2 months (range, 7.6– 33.3 months), the investigator and blinded independent central review-assessed ORR were 80.6% and 77.4%, respectively. A total of 33 patients (53.2%) reached the standard of conversion to resectable HCC and 29 patients underwent resection. The median interval between start of triple therapy and resection was 123 days (range, 55– 372 days). Pathological complete response and major pathological response were observed in 16 and 24 patients, respectively. Median overall survival and progression-free survival were not reached. Treatment-related adverse events occurred in 74.2% of the patients (grade ≥ 3, 14.5%; grade ≥ 4, 4.8%).Conclusion: Combination of LEN, PD-1 and TACE showed a high rate of tumor response and convert resection in uHCC patients, with manageable toxicity.Keywords: unresectable hepatocellular carcinoma, tumor response, adverse events, combination therapy, monotherapy

Background Neuropathic pain is a debilitating disease with few effective treatments. Emerging evidence indicates the involvement of mitochondrial dysfunction and oxidative stress in neuropathic pain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a potent regulator of the antioxidant response system. In this study, we investigated whether RTA-408 (RTA, a novel synthetic triterpenoid under clinical investigation) could activate Nrf2 and promote mitochondrial biogenesis (MB) to reverse neuropathic pain and the underlying mechanisms. Methods Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Pain behaviors were measured via the von Frey test and Hargreaves plantar test. The L4-6 spinal cord was collected to examine the activation of Nrf2 and MB. Results RTA-408 treatment significantly reversed mechanical allodynia and thermal hyperalgesia in CCI mice in a dose-dependent manner. Furthermore, RTA-408 increased the activity of Nrf2 and significantly restored MB that was impaired in CCI mice in an Nrf2-dependent manner. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) is the key regulator of MB. We found that the PGC-1α activator also induced a potent analgesic effect in CCI mice. Moreover, the antinociceptive effect of RTA-408 was reversed by the preinjection of the PGC-1α inhibitor. Conclusions Nrf2 activation attenuates chronic constriction injury-induced neuropathic pain via induction of PGC-1α-mediated mitochondrial biogenesis in the spinal cord. Our results indicate that Nrf2 may be a potential therapeutic strategy to ameliorate neuropathic pain and many other disorders with oxidative stress and mitochondrial dysfunction.

BackgroundNeuropathic pain is a debilitating disease with few effective treatments. Emerging evidence indicates the involvement of mitochondrial dysfunction and oxidative stress in neuropathic pain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a potent regulator of antioxidant response system. In this study, we investigated whether RTA-408 (a novel synthetic triterpenoid under clinical investigation) could activate Nrf2 and promote mitochondrial biogenesis (MB) to reverse neuropathic pain and the underlying mechanisms.MethodsNeuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. Pain behaviors were measured via the von-Frey test and Hargreaves plantar test. The L4-6 spinal cord was collected to examine the activation of Nrf2 and MB.ResultsRTA-408 treatment significantly reversed mechanical allodynia and thermal hyperalgesia in CCI mice in a dose-dependent manner. Furthermore, RTA-408 increased the activity of Nrf2 and significantly restored MB that was impaired in CCI mice in an Nrf2 dependent manner. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) is the key regulator of MB. We found that PGC-1α activator also exhibited a potent analgesic effect in CCI mice. Moreover, the antinociceptive effect of RTA-408 was reversed by the pre-injection of PGC-1α inhibitor.ConclusionsNrf2 activation attenuates chronic constriction injury-induced neuropathic pain via induction of PGC-1α-mediated mitochondrial biogenesis in the spinal cord. Our results indicate that Nrf2 may be a potential therapeutic strategy to ameliorate neuropathic pain and many other disorders with oxidative stress and mitochondrial dysfunction.

Superheated steam is the main medium in the piping system of steam power plants. In these pipelines, perforated plates are widely used to regulate the flow rate, pressure, and also reduce aerodynamics noise of steam. For the superheated steam flow, the flow resistance and aerodynamic noise are two key parameters of the perforated plates. In order to investigate the flow resistance and steam aerodynamic characteristics, this paper presents a systematic study of superheated steam and water through multi-stage perforated plates under a wide range of operating conditions with both experimental and numerical methods. The experiments are conducted out to validate the applicability of the adopted numerical models. Then numerical methods are used to investigate the water flow resistance and the Mach number distributions of the steam flow with different structural parameters. The results show that with the increase of the holes diameter, the pressure drop decreases and the Mach number increases. Mach number drops significantly when the position of side holes moves towards the edge of the perforated plate. A critical stage distance is found, at which the pressure drop has the maximum value. Besides, the occurrence probability of supersonic steam flow increases as the decrease of stage distance under a restricted space, and the disturbed length of supersonic steam flow is longer when the stage distance is smaller. This work can be referred by someone who deals with perforated plate design in steam piping systems or related research topics.

Hydrogen fuel cell is an ideal power source for electric vehicles. For a hydrogen fuel cell electric vehicle, the hydrogen is reserved in a high pressure level to promote the recharge mileage while relatively low-pressure hydrogen is demanded for proper functioning of the fuel cell stack, so that decompression of hydrogen is needed before hydrogen flowing into the fuel cell. With a reverse flow through Tesla valves, there appears a large pressure drop between the inlet and outlet, which can be used for hydrogen decompression nicely. However, a single-stage Tesla valve cannot meet the pressure drop requirement, so multi-stage Tesla valves are utilized. In this paper, numerical simulations of reversed hydrogen flow through multi-stage Tesla valves are carried out. The stage number of multi-stage Tesla valves and the inlet/outlet pressure ratio are both studied, and the distributions of temperature, pressure, and velocity inside multi-stage Tesla valves are all investigated. Results show that as the stage number increases or the inlet/outlet pressure ratio decreases, the pressure and the velocity inside multi-stage Tesla valves decrease, and the less the stage number, the more possibility for the velocity higher than local acoustic speed. Besides, a power-law relationship between the flow rate, the stage number and pressure ratio is summarized.

Paclitaxel-induced neuropathic pain (PINP) is a progressive and refractory side effect of chemotherapy with few effective treatments at present. It is well-established that astrocytes activation contributes to the development of PINP. Recent reports showed astrocytes can be divided into A1 and A2 phenotypes. However, whether the transformation of astrocytes participates in PINP and the underlying mechanisms remain unknown. As Notch signaling pathway have shown to be involved in neuropathic pain, we aimed to investigate the relationship between Notch signaling pathway and A1 astrocytes in PINP. Herein we found that both A1 astrocytes and Notch signaling were markedly activated in the spinal cord of PINP rats and the downstream molecules of Notch signaling were colocalized with A1 astrocytes. DAPT (an inhibitor of Notch signaling) not only suppressed the mechanical allodynia of PINP rats, but also inhibited the activation of Notch signaling pathway and A1 astrocytes. Furthermore, Jagged1 (a ligand of Notch1 receptors) dose-dependently induced mechanical hyperalgesia in naïve rats and simultaneously led to Notch signaling activation and A1 astrocytes transformation, all of which were inhibited by DAPT. Taken together, these results demonstrate Notch signaling activation contributes to PINP via A1 astrocytes activation, which provides a promising therapeutic target for PINP.

Neuropathic pain places a devastating health burden, with very few effective therapies. We investigated the potential antiallodynic and antihyperalgesic effects of apigenin, a natural flavonoid with momoamine oxidase (MAO) inhibitory activity, against neuropathic pain and investigated the mechanism(s).The neuropathic pain model was produced by chronic constriction injury of sciatic nerves in male C57BL/6J mice, with pain-related behaviours being assayed by von Frey test and Hargreaves test. In this model the role of 5-HT and 5-HTApigenin repeated treatment (p.o., once per day for 2 weeks), in a dose-related manner (3, 10 and 30 mg·kgApigenin antiallodynic and antihyperalgesic actions against neuropathic pain crucially involve spinal 5-HT

Background Bile duct invasion is a relatively rare event and is not well characterised in hepatocellular carcinoma (HCC). It remains very difficult to diagnose HCC with bile duct tumour thrombus (BDTT) before surgery. Increasing evidence has revealed that inflammation plays a critical role in tumorigenesis. This study aimed to develop nomograms based on systemic and hepatic inflammation markers to predict microscopic BDTT (micro-BDTT) before surgery in HCC. Methods A total of 723 HCC patients who underwent hepatectomy as initial therapy between January 2012 and June 2020 were included in the study. Logistic regression analysis was used to identify independent risk factors for micro-BDTT. The nomograms were constructed using significant predictors, including α-fetoprotein (AFP), alkaline phosphatase (ALP), direct bilirubin (DB), prognostic nutritional index (PNI), and γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT). The prediction accuracies of the nomograms were evaluated using the area under the receiver operating characteristic (ROC) curve. Results AFP, ALP, DB, PNI, and γ-GT/ALT were independent risk factors for predicting micro-BDTT (P = 0.036, P = 0.004, P = 0.013, P = 0.012, and P = 0.006, respectively), which were assembled into the nomograms. The area under the ROC curve of the nomograms combining PNI and γ-GT/ALT for predicting micro-BDTT was 0.804 (95% confidence interval [CI]: 0.730–0.878). The sensitivity and specificity values when used in predicting micro-BDTT before surgery were 0.739 (95% CI: 0.612–0.866) and 0.781 (95% CI: 0.750–0.813), respectively. Conclusions The nomogram based on combining systemic and hepatic inflammation markers is suitable for predicting micro-BDTT before surgery in HCC patients, leading to a rational therapeutic choice for HCC.

Background Surgical resection is the primary treatment for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT). This study was conducted to investigate the efficacy of postoperative adjuvant TACE (PA-TACE) in patients with HCC and BDTT. Methods Data from patients who underwent surgery for HCC with BDTT at two medical centers were retrospectively analyzed. The survival outcomes of patients who were treated by hepatic resection followed by PA-TACE were compared with those of patients who underwent surgery alone. Propensity score matching (PSM) analysis was performed with a 1:1 ratio. Results Of the 308 consecutively enrolled HCC patients with BDTT who underwent surgical resection, 134 underwent PA-TACE whereas 174 underwent surgery alone. From the initial cohort, PSM matched 106 pairs of patients. The OS and DFS rates were significantly better for the PA-TACE group than the surgery alone group (for OS: before PSM, P = 0.026; after PSM, P = 0.039; for DFS: before PSM, P = 0.010; after PSM, P = 0.013). Conclusion PA-TACE was associated with better survival outcomes than surgery alone for patients with HCC and BDTT. Prospective clinical trials are warranted to validate the beneficial effect of PA-TACE on HCC patients associated with BDTT.

We propose a controllable non-reciprocal transmission model. The model consists of a Mobius ring, which is connected with two one-dimensional semi-infinite chains, and with a two-level atom located inside one of the cavities of the Mobius ring. We use the method of Green function to study the transmittance of a single photon through the model. The results show that the non-reciprocal transmission can be achieved in this model and the two-level atom can behave as a quantum switch for the non-reciprocal transport of the single photon. This controllable non-reciprocal transmission model may inspire new quantum non-reciprocal devices., 7 pages, 6 figures

L oilfield is a layered sandstone gas cap oilfield controlled by structure. The gas is on the top of the structure. On the plane, the oil and gas are distributed in a ring belt, and the area of gas cap from top to bottom is gradually smaller. In the early stage of development, in order to maintain the stability of oil-gas interface and prevent oil and gas channeling, a certain width of unperforated oil ring is left outside the gas cap as a buffer zone for oil and gas migration. At present, the whole oilfield has entered the stage of ultra-high water cut development. In order to effectively develop the reserves in buffer zone and explore the reasonable development mode of the gas cap reservoir, reservoir structure, development characteristics, migration law of oil and gas in buffer zone and distribution characteristics of remaining oil potential were fully considered, and the development effects of different flooding methods such as water injection barriers, polymer injection barriers, gas flooding, water flooding, were comprehensively compared. The development mode of polymer injection barrier is optimized through comprehensive comparison. It is estimated that the recovery ratio will be increased by more than 20% points, which can provide important technical reserves for the effective development of layered gas cap reservoirs in ultra-high water cut stage.

LaSaXing oilfield has entered the late ultra-high water cut stage after 60-year development, the dominant oil reservoirs are exploited in 3 flooding modes - water flooding, polymer flooding and ASP flooding. Fine recognition of residual oil distribution under different flooding conditions is the key to make precise adjustment and tapping oil potential. Based on stratum division and correlation, a comparison analysis was taken on the water-washing characteristics and residual oil distribution of dominant reservoirs according to the 68 core wells analysis data in LaSaXing oilfield. The results show that the degree of water-washing is aggravated in dominant reservoir and the strong and medium water-washing distribution proportion is high, where only 20% of sandstone thickness is not water-washed. The residual oil in the dominant reservoir after water flooding development is mainly distributed at the top of the positive rhythm reservoir, and some plane residual oil stagnant areas are formed due to the non-controlled water pattern. The residual oil in the dominant reservoir after polymer flooding development is mainly distributed in the medium and low water-washing area controlled by rhythm and inter-layers, and the plane residual oil stagnant area is mainly on both sides away from the main stream line of injection wells. The residual oil in the dominant reservoir after ASP flooding development is mainly distributed in the upper part of thick layer and the top of rhythm section longitudinally, and the plane residual oil stagnant area is mainly distributed near the production end. The comprehensive research on the water-washing characteristics of different flooding modes shows that even if the main reservoir of old oilfield has been developed and adjusted for many cycles over a long period, it still has oil potential for further enhanced oil recovery, and the main geological factors that control the distribution of residual oil have changed from sedimentary micro-facies to various micro-scale geological interfaces.

Eleven oil and gas reservoirs formation during the Sinian - Jurassic period have great reserves in the northeast area of Sichuan Basin, and the DS survey of Yilong - Pingchang area is a block with great exploration potential. DS 3D seismic survey is located in the mountainous surface situation is very complex, the elevation difference of two detection points in adjacent 2 km is more than 1000 m, the underground structure undulating fault develops various disturbance wave fields complex, the statics problem is very prominent. The aim of this exploration is to identify the shallow channel of shallow Xujiahe formation, the statics problem of shallow thin layer of low SNR seismic data in double complex area must be solved before migration. By means of 3D Fresnel band chromatography statics correction technique, the continuity of the events in frequency band range of 8–28 Hz is improved. In order to solve the problems of low SNR and difficulty in velocity analysis, we use large-scale parameter denoising mesh speed analysis iteration to improve the accuracy of speed analysis, using the precise superposition speed using the super-trace residual statics technology, divided into three rounds gradually expand the data frequency band involved in the operation for residual statics processing. The final residual statics is less than ±0.5 ms, there is a significant improvement in the continuity of the events compared with the results of the previous treatment, the characteristics of vertical wave resistance are clearer, the resolution ability of small horizontal geological bodies is improved obviously than before, and the characteristics of channel in Xujiahe formation are easier to identify, which provides high quality results for seismic target exploration in Yilong - Pingchang area of Sichuan Basin.

For solving the problems of high dispersion of residual oil and low accuracy of residual oil description in late ultra-high water cut stage, a study on the integration technology of modeling and numerical simulation was carried out with X6D block as the target area, which had an area of 9.7 km2 and contains 586 wells with 100 sedimentary units. A small-scale, non-coarsening modeling and numerical simulation method had been provided to fulfill the anatomy of single sand body and internal architecture according to the geological idea of “defining vertical period, demarcating lateral boundary and identifying sedimentary pattern”. The two-step shale bedding fitting modeling with small-scale grid of 15 m × 15 m × 0.15 m was applied to establish fine 3D model, which included the internal architecture distribution information. At the same time, the grid non-coarsening and structured division technique were used in numerical simulation for better convergence and higher operation efficiency, which implemented the numerical simulation of 10.02 million node model in the study area. The simulation revealed that micro-geological boundaries such as interlayer rhythm and shale bedding control the distribution of residual oil. Based on the result, the paper established two interbeded flooding patterns of various types of sand bodies as “Uniform pattern” and “Penetration pattern”, quantified the distribution rules of interlayer residual oil and dominant seepage channels in thick oil layers, and effectively guided the optimal selection of fracturing and water shutoff measures in the study area. By the comparison of 7 wells before and after fracturing, a good development effect was obtained with the average oil production of single well increased by 3.74 t/d, the water content decreased by 3.21%, and the accumulated oil production increased by 5769.5 t within the effective period, which proved the wide application prospect of small-scale, non-coarsening numerical simulation technology in late ultra-high water cut stage.

As one of the primary sedimentary reservoirs in river delta sediment deposition system, meandering deposits have important academic value and huge hydrocarbon potential, and thus have been always the hot spot in the study of continental sandstone sedimentation worldwide. Over more than 60 years of research, significant progress has been made in many respects, meanwhile, some controversies still exist, especially on the sedimentary structure and internal architecture of different types of meandering rivers. By using the comprehensive principle of sedimentary physical simulation and reservoir architecture analysis, flume simulation tests of meandering river architecture were designed on PI2 layer of Daqing oilfield. Based on the sedimentary background of the study area, the X direction and Y direction length of flume model were 5 m and 12 m respectively, the bottom slope was about 0.5° to 1°, the total range of active subsidence was 16 cm, and the flow ratio of flood period - medium period - dry period was 6:3:1. The sand body solid model was established through 4 rounds of experiments, and the meandering river architecture was described during the course of the experiment. The result shows that there are 7 types of architecture units with different characteristics in meandering sediments, and point bar is the main unit. Controlled by deposition mechanism and hydrodynamic condition, the lateral accretion body of point bar can be categorized into 3 types, different type of which has distinct development scale and accretion dip. The lateral accretion shale beds of single body in meandering deposits appears to dip angle of about 10°, upper dense and thick, lower sparse and thin. The shale beds extend down to the 1/2–2/3 thickness of the whole sandbody with the spatial scale spread to the 1/2–2/3 width of single body. This study has a potentially important significance in guiding prediction of sandstones and distribution of residual oil in this type of oilfields.

e13023 Background: Human epidermal growth factor receptor-2 (HER2) positive breast cancer is a growing concern due to the boom in anti-HER2 therapy. Trastuzumab as the most classic anti-HER2 therapy drug, combined with chemotherapy has become the standard first-line treatment for advanced HER2-positive (HER2+) patients. Although some real-world studies of trastuzumab have been reported, less is known about the role of hormone receptors (HR) in first-line combined therapy. For maintenance therapy after chemotherapy combined with anti-HER2 therapy, the guidance given by clinical trials is the maintenance of targeted therapy. However, for those with HER2+/HR-positive (HR+) breast cancer, whether adding endocrine maintenance therapy can benefit progression-free survival (PFS) in addition to anti-HER2 therapy still needs more research. Thus, the purpose of this study was to retrospectively analyze real-world data, determine the factors that influence the trastuzumab-based therapy in advanced HER2-positive breast cancer patients. Methods: We retrospectively collected the treatment information of advanced breast cancer patients underwent first-line chemotherapy with trastuzumab from 2012 to 2021 in Zhejiang Cancer Hospital. Kaplan–Meier analysis and Cox regression methods were used to calculate and compare the PFS. Results: The study finally enrolled 285 patients meeting the requirement, including 150 HER2+/HR-negative (HR-) and 135 HER2+/HR+ (triple-positive) patients. The median chemotherapy treatment cycles and trastuzumab cycles were 7 (6-8) and 12 (7-17) cycles, respectively. For triple-positive breast cancer, maintenance endocrine therapy was aslo given concurrently with trastusumab in 75 patients after chemotherapy and trastusumab. Overally, the median PFS of first-line treatment was 11.73 (10.16-13.30) months, which was consistent with literature reports. Multivariate analysis revealed that HR positive [hazard ratio, 0.69; 95% confidence interval (CI), 0.52–0.92; P= 0.010], and non-brain metastasis (hazard ratio, 0.54; 95% CI, 0.29–0.99; P= 0.048) were independent prognostic factors. Further Kaplan–Meier analysis demonstrated triple-positive patients with maintenance endocrine therapy significantly had longer PFS than triple-positive patients without maintenance endocrine therapy and HER2+/HR- patients (21.33m vs. 10.13m vs. 9.53m, respectively, P < 0.001). Conclusions: HR-positive was an independent prognostic factor for HER2-positive advanced breast cancer patients receiving first-line chemotherapy with trastuzumab. And endocrine therapy combined trastuzumab as Maintenance after chemotherapy prolonged PFS in HR-positive subgroup patients.

e13024 Background: The immune system reveals to play a pivotal role in HER2 positive breast cancer responsiveness to trastuzumab therapy. The platelet-lymphocyte ratio (PLR) is representative blood markers of systemic inflammatory responses. It is suggested as an immunity biomarker in gastric, lung cancer and other cancers, but is less well known in breast cancer. The aim of this study is to investigate the predictive role of PLR in HER2 positive metastatic breast cancer patients treated with first-line trastuzumab therapy. Methods: This study retrospectively includes 287 HER2 positive metastatic breast cancer patients with first-line trastuzumab therapy in Cancer Hospital of the University of Chinese Academy of Science from January 2010 to November 2021. The Peripheral blood cell count of these patients before trastuzumab treatment is evaluated to calculate PLR. All patients are separated into PLRhigh or PLRlow cohort according to cut-off value defined as median value. Median value of PLR is 154.5, more than 154.5 is defined by PLRhigh, otherwise defined as PLRlow. Kaplan–Meier curves is performed to assess progression-free survival (PFS). Univariate and multivariate analyses were performed using a logistic regression model. Results: Of 287 patients, 228 patients’ peripheral blood cell count were available. 114 patients are PLRhigh and 114 patients are PLRlow. Patients with PLRhigh achieved a significantly worse PFS compared to those with PLRlow (median PFS: 8.47 months vs.9.92 months, HR:1.475, 95% CI:1.068-2.038, P = 0.014). Besides, mean corpuscular volume (< 89.2fL), lymphocyte (< 1.3), mean hemoglobin (< 30PG) are also related to worse PFS ( P= 0.003,0.033,0.055,respectively). Importantly, PLRhigh, mean corpuscular volume, remain independent predictors in the multivariate COX analysis (HR 0.689,95%CI 0.493-0.962, P = 0.028;HR1.646,95%CI 1.177-2.302, P = 0.004). Conclusions: Patients with pre-treatment PLRhigh showed less sensitivity to trastuzumab therapy for metastatic breast cancer patients independent of other molecular characteristics. The pre-treatment PLR levels might serve as a predictive biomarker for HER2 positive breast cancer with trastuzumab therapy.

BACKGROUND Laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct (CBD) exploration (LCBDE) is one of the main treatments for choledocholithiasis with CBD diameter of larger than 10 mm. However, for patients with small CBD (CBD diameter ≤ 8 mm), endoscopic sphincterotomy remains the preferred treatment at present, but it also has some drawbacks associated with a series of complications, such as pancreatitis, hemorrhage, cholangitis, and duodenal perforation. To date, few studies have been reported that support the feasibility and safety of LCBDE for choledocholithiasis with small CBD. AIM To investigate the feasibility and safety of LCBDE for choledocholithiasis with small CBD. METHODS A total of 257 patients without acute cholangitis who underwent LC + LCBDE for cholecystolithiasis from January 2013 to December 2018 in one institution were reviewed. The clinical data were retrospectively collected and analyzed. According to whether the diameter of CBD was larger than 8 mm, 257 patients were divided into large CBD group (n = 146) and small CBD group (n = 111). Propensity score matching (1:1) was performed to adjust for clinical differences. The demographics, intraoperative data, short-term outcomes, and long-term follow-up outcomes for the patients were recorded and compared. RESULTS In total, 257 patients who underwent successful LC + LCBDE were enrolled in the study, 146 had large CBD and 111 had small CBD. The median follow-up period was 39 (14-86) mo. For small CBD patients, the median CBD diameter was 0.6 cm (0.2-2.0 cm), the mean operating time was 107.2 ± 28.3 min, and the postoperative bile leak rate, rate of residual CBD stones (CBDS), CBDS recurrence rate, and CBD stenosis rate were 5.41% (6/111), 3.60% (4/111), 1.80% (2/111), and 0% (0/111), respectively; the mean postoperative hospital stay was 7.4 ± 3.6 d. For large CBD patients, the median common bile duct diameter was 1.0 cm (0.3-3.0 cm), the mean operating time was 115.7 ± 32.0 min, and the postoperative bile leak rate, rate of residual CBDS, CBDS recurrence rate, and CBD stenosis rate were 5.41% (9/146), 1.37% (2/146), 6.85% (10/146), and 0% (0/146), respectively; the mean postoperative hospital stay was 7.7 ± 2.7 d. After propensity score matching, 184 patients remained, and all preoperative covariates except diameter of CBD stones were balanced. Postoperative bile leak occurred in 11 patients overall (5.98%), and no difference was found between the small CBD group (4.35%, 4/92) and the large CBD group (7.61%, 7/92). The incidence of CBDS recurrence did not differ significantly between the small CBD group (2.17%, 2/92) and the large CBD group (6.52%, 6/92). CONCLUSION LC + LCBDE is safe and feasible for choledocholithiasis patients with small CBD and did not increase the postoperative bile leak rate compared with chole-docholithiasis patients with large CBD.

Anatomic resection (AR) of the liver is generally recommended in hepatocellular carcinoma (HCC) patients. However, the benefits of AR and nonanatomic resection (NAR) in HCC patients with bile duct tumor thrombus (BDTT) are unknown. This study aimed to compare long-term outcomes of AR and NAR in HCC patients with BDTT after curative resection. A total of 175 consecutive HCC patients with BDTT after curative resection between April 2009 and December 2017 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Recurrence-free survival (RFS) and overall survival (OS) were compared between the cohorts. After PSM, 120 patients were analyzed. The AR group had better RFS than the NAR group (P = 0.010). Even though there was no statistically significant difference in OS (P = 0.140, power = 0.33), the 3- and 5-year OS rates in the AR group (52.4% and 44.2%, respectively) were obviously higher than those in the NAR group (35.4% and 30.4%, respectively). When patients were further stratified according to tumor size, better RFS and OS were observed in patients with small (≤ 5 cm) tumors after AR (P < 0.001 and P = 0.004, respectively). Multivariate analysis identified AR (P = 0.024) as an independent favorable prognostic factor for RFS in HCC patients with BDTT. AR is recommended for HCC patients with BDTT, especially in patients with small (≤ 5 cm) tumors.

Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide; however, accurate prognostic tools are still lacking. We aimed to identify immunohistochemistry (IHC)-based signature as a prognostic classifier to predict recurrence and survival in patients with HCC at Barcelona Clinic Liver Cancer (BCLC) early- and immediate-stage. In total, 567 patients who underwent curative liver resection at two independent centers were enrolled. The least absolute shrinkage and selection operator regression model was used to identify significant IHC features, and penalized Cox regression was used to further narrow down the features in the training cohort (n = 201). The candidate IHC features were validated in internal (n = 101) and external validation cohorts (n = 265). Three IHC features, hepatocyte paraffin antigen 1, CD34, and Ki-67, were identified as candidate predictors for recurrence-free survival (RFS), and were used to categorize patients into low- and high-risk recurrence groups in the training cohort (P < 0.001). The discriminative performance of the 3-IHC_based classifier was validated using internal and external cohorts (P < 0.001). Furthermore, we developed a 3-IHC_based nomogram integrating the BCLC stage, microvascular invasion, and 3-IHC_based classifier to predict 2- and 5-year RFS in the training cohort; this nomogram exhibited acceptable area under the curve values for the training, internal validation, and external validation cohorts (2-year: 0.817, 0.787, and 0.810; 5-year: 0.726, 0.662, and 0.715; respectively). The newly developed 3-IHC_based classifier can effectively predict recurrence and survival in patients with early- and intermediate-stage HCC after curative liver resection.

Compared to conventional globe valves, the pilot-control globe valve (PCGV) possesses advantages of lower energy consumption and higher space utilization. In order to analyze the effects of pilot pipe and damping orifice arrangements, this work proposes four PCGVs and conducts simulations to compare their overall performances, overall flow characteristics, and local flow characteristics around the valve core. In general, the arrangement of the pilot pipe has larger effects on the hydroperformances of PCGVs than the arrangement of the damping orifice. The pipe-parallel-mounted type PCGV performs better in hydroperformance than the pipe-perpendicular-mounted type PCGV, and thus is recommended in practice. As the specified valve core travel increases, the flow resistance of PCGVs decreases and the flow capacity of PCGVs increases. However, overlarge specified valve core travel has little effects on the flow resistance and flow capacity of PCGVs. Besides, the increased specified valve core travel could effectively reduce the wear induced by the uneven pressure distribution on the external lateral face of valve core, but it has little effect on the wear induced by the uneven pressure distribution on the bottom face. For all pipe-perpendicular-mounted type PCGVs, the variation of axial force imposed on the valve core relative to the specific valve core travel presents similar tendencies under different incoming flow velocity within the scope of the investigation, which could be concluded into a fitting equation. This work could be referred for the optimization of PCGVs and other similar valves.

Chronic neuropathic pain poses a significant health problem, for which effective therapy is lacking. The current work aimed to investigate the potential antinociceptive efficacy of isorhynchophylline, an oxindole alkaloid, against neuropathic pain and elucidate mechanisms. Male C57BL/6J mice were subjected to chronic constriction injury (CCI) by loose ligation of their sciatic nerves. Following CCI surgery, the neuropathic mice developed pain-like behaviors, as shown by thermal hyperalgesia in the Hargreaves test and tactile allodynia in the von Frey test. Repetitive treatment of CCI mice with isorhynchophylline (p.o., twice per day for two weeks) ameliorated behavioral hyperalgesia and allodynia in a dose-dependent fashion (5, 15, and 45 mg/kg). The isorhynchophylline-triggered antinociception seems serotonergically dependent, since its antinociceptive actions on neuropathic hyperalgesia and allodynia were totally abolished by chemical depletion of spinal serotonin by PCPA, whereas potentiated by 5-HTP (a precursor of 5-HT). Consistently, isorhynchophylline-treated neuropathic mice showed escalated levels of spinal monoamines especially 5-HT, with depressed monoamine oxidase activity. Moreover, the isorhynchophylline-evoked antinociception was preferentially counteracted by co-administration of 5-HT1A receptor antagonist WAY-100635. In vitro, isorhynchophylline (0.1-10 nM) increased the Emax (stimulation of [35S] GTPγS binding) of 8-OH-DPAT, a 5-HT1A agonist. Of notable benefit, isorhynchophylline was able to correct co-morbidly behavioral symptoms of depression and anxiety evoked by neuropathic pain. Collectively, these findings confirm, for the first time, the disease-modifying efficacy of isorhynchophylline on neuropathic hypersensitivity, and this effect is dependent on spinal serotonergic system and 5-HT1A receptors.

The BWH (broadband excitation receiving, wide azimuth observation, high density acquisition) seismic data size deployed in the deep complex tectonic area of the northern Songliao Basin was 7.5T, and the surface elevation of the study area varies greatly. The single point receiving observing system with high density and small cells presents a new challenge to static processing. The pick-up precision of the first break wave directly determines whether the static correction is accurate or not. The conventional method can pick up the first break wave in the shot domain, and the precision of the pick-up quantity cannot be required by the static correction of tomography. In this paper, according to the characteristics of BHW mass data, a new method is proposed to separate the data into small pick-up units by using detection lines as picking units and dividing offset groups into small pick-up units. The trend line which controls the pick-up accuracy is adapted to the influence of the far and near offset at the same time, and the pick-up accuracy is greatly improved. The static correction effect is achieved by the method of model-constrained travel-time tomography static correction. This method is especially suitable for BWH seismic data and other big offset data, the first break wave pick-up of high-density 3D seismic data received by single detect point can improve the pick-up accuracy to the maximum extent, and has wide application and popularization space.

As a key device influencing the safety and the economy of nuclear power plants simultaneously, the main feed water regulating valve (MFWRV) controls the flow rate flowing to the steam generator. In this work, modal and structural analysis is conducted under different loading conditions to investigate vibration characteristics and mechanical characteristics of MFWRV. The results show that the combination of loading conditions has little effect on the natural frequency and the mode shape of MFWRV. However, it influences the results of structural analysis significantly. Compared with the fixed internal pressure, the variable internal pressure promoted the maximum stress intensity when the valve opening (L/Lmax) is smaller than 80%. The maximum deformation when the seismic load is considered is almost three times as large as it when the seismic is not considered. The seismic load always has a positive effect on the maximum gap (gmax) between the valve core and the sleeve. However, the variable internal pressure only has a positive effect on gmax relative to the fixed internal pressure when L/Lmax = 40 ~ 90%. Besides, the variable internal pressure has an evident negative effect on the maximum sliding distance (sdmax) between the valve core and the sleeve relative to the fixed internal pressure under the low and the middle valve opening. This work provides a reference for the structural design of the main feed water valve and other similar valves.

Inflammatory external root resorption (IERR) refers to the pathological process of dissolving the hard tissue on the outer surface of the tooth root by the body's own immune system under the stimulation of various physical and chemical factors such as infection, stress, trauma and orthodontic treatment. Severe IERR can lead to endodontic and periodontal diseases, and even the loss of teeth. Therefore, understanding the etiology and the pathogenic mechanism of IERR are of importance in its prevention and treatment. This article will review the etiology and the regulation mechanisms of IERR.炎症性牙根外吸收是指在感染、压力、创伤及正畸治疗等多种物理化学因素刺激下人体自身免疫系统溶解牙根外表面硬组织的病理性过程。严重的炎症性牙根外吸收可导致牙体牙髓、牙周疾病，甚至牙缺失。因此，了解其致病机制对预防及治疗炎症性牙根外吸收有重要意义。本文对炎症性牙根外吸收的致病机制进行综述。.

To guarantee accurate flux regulation and safe running state, precise design for each part of valves is required. Aiming at studying the effect of the valve core shape on flow characteristics inside a sleeve regulating valve, numerical simulation under different valve core shapes is conducted. To begin with, the outlet flux under different valve core shapes and valve openings is obtained, and flux curves for each valve core shape are compared. Then, internal flow characteristics including pressure and velocity distribution are discussed to get a deeper understanding of the relationship between the flow mechanism and the valve core shape. The results show that the variation of the valve core shape has conspicuous effects on flow characteristics inside the sleeve regulating valve. This paper provides a reference for researchers engaged with designing sleeve regulating valves and other similar valves.

The existing seismic data in the deep layer of Songliao Basin have low vertical resolution, poor imaging accuracy and weak ability to depict anisotropy of seismic data, so the seismic data can not meet the geological requirements of fine target characterization. In order to identify thinner reservoirs and smaller faults in deep and complex structural areas, to complete sequence subdivision on volcanic rocks of Yingcheng formation and the dense sand of Shahezi formation, BWH seismic data acquisition is deployed in Anda sag. Aiming at the characteristics of clear description of BWH wave field but low SNR. A Full-frequency Fidelity and Amplitude preserving processing Technology (Flow) supported by surface consistent time-varying pulse deconvolution and viscoelastic medium prestack time migration and depth migration techniques is formed. Compared with the old data, the target band width of the BWH data has been widened by 15 Hz, the imaging quality of the complex structural area is improved obviously, and the prediction coincidence rate of the thin sand body over 8m is increased by more than 10 percentage points. The thin interbed is developed in continental sedimentary basin, and the horizontal heterogeneity is serious. The BWH acquisition and full frequency amplitude preserving processing technology will bring a new solution for fine target exploration in deep and complex structural area of Continental Sedimentary basin.

Background Hepatocellular carcinoma (HCC) associated with bile duct tumor thrombus (BDTT) is uncommon in clinical practice. Surgical resection can achieve better survival than non-operative palliative treatments. However, there is great controversy regarding the optimal surgical modality, particularly regarding the approach to remove BDTT in patients with HCC with macroscopic BDTT. Methods Data from consecutive patients who underwent radical surgery for HCC and macroscopic BDTT at the Eastern Hepatobiliary Surgery Hospital and Fujian Provincial Hospital from January 2009 to December 2016 were retrospectively reviewed. The survival outcomes of patients who underwent hepatectomy combined with extrahepatic bile duct resection (the EBDR group) were compared with those of patients undergoing liver resection plus thrombectomy (the thrombectomy group) using propensity score matching (PSM). Univariate and multivariate Cox analyses were performed to identify independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Results 217 patients included in this study were divided into two groups: the EBDR group (n=30) and the thrombectomy group (n=187). A total of 90 patients were matched by PSM with a 1:2 ratio. Before PSM, the OS and RFS rates were comparable between the two groups (for OS, P=0.517; for RFS, P=0.211). After PSM, the OS rates did not differ statistically significantly between the EBDR and thrombectomy groups (P=0.134). Nevertheless, the RFS rate of the EBDR group was significantly higher compared to that of the thrombectomy group (P=0.020). Multivariate analysis demonstrated that some traditional risk factors, such as tumor size and microscopic resection margin, were more important prognostic factors than the BDTT type. Conclusions For patients with HCC and macroscopic BDTT, hepatectomy combined with extrahepatic bile duct resection is associated with a reduced recurrence rate in comparison with concurrent thrombectomy. Further large-scale, prospective studies are warranted to evaluate the impact of different surgical modalities on these patients' survival.

Considering the complicated pathogenesis of Alzheimer's disease (AD), multi-targets have become a focus in the discovery of drugs for treatment of this disease. In the current work, we established a multi-target strategy for discovering active reagents capable of suppressing both Aβ level and Tau hyperphosphorylation from natural products, and found that the ethanol extract of Thamnolia vermicularis (THA) was able to improve learning ability in APP/PS1 transgenic mice by inhibiting both Aβ levels and Tau hyperphosphorylation. SH-SY5Y and CHO-APP/BACE1 cells and primary astrocytes were used in cell-based assays. APP/PS1 transgenic mice [B6C3-Tg(APPswe, PS1dE9)] were administered THA (300 mg·kg-1·d-1, ig) for 100 d. After the administration was completed, the learning ability of the mice was detected using a Morris water maze (MWM) assay; immunofluorescence staining, Congo red staining and Thioflavine S staining were used to detect the senile plaques in the brains of the mice. ELISA was used to evaluate Aβ and sAPPβ contents, and Western blotting and RT-PCR were used to investigate the relevant signaling pathway regulation in response to THA treatment. In SH-SY5Y cells, THΑ (1, 10, 20 μg/mL) significantly stimulated PI3K/AKT/mTOR and AMPK/raptor/mTOR signaling-mediated autophagy in the promotion of Aβ clearance as both a PI3K inhibitor and an AMPK indirect activator, and restrained Aβ production as a suppressor against PERK/eIF2α-mediated BACE1 expression. Additionally, THA functioned as a GSK3β inhibitor with an IC50 of 1.32±0.85 μg/mL, repressing Tau hyperphosphorylation. Similar effects on Aβ accumulation and Tau hyperphosphorylation were observed in APP/PS1 transgenic mice treated with THA. Furthermore, administration of THA effectively improved the learning ability of APP/PS1 transgenic mice, and markedly reduced the number of senile plaques in their hippocampus and cortex. The results highlight the potential of the natural product THA for the treatment of AD.

Manipulation of biofilm formation in Shewanella is beneficial for application to industrial and environmental biotechnology. BpfA is an adhesin largely responsible for biofilm formation in many Shewanella species. However, the mechanism underlying BpfA production and the resulting biofilm remains vaguely understood. We previously described the finding that BpfA expression is enhanced by DosD, an oxygen-stimulated diguanylate cyclase, under aerobic growth. In the present work, we identify FlrA as a critical transcription regulator of the bpfA operon in Shewanella putrefaciens CN32 by transposon mutagenesis. FlrA acted as a repressor of the operon promoter by binding to two boxes overlapping the −10 and −35 sites recognized by σ 70 . DosD regulation of the expression of the bpfA operon was mediated by FlrA, and cyclic diguanylic acid (c-di-GMP) abolished FlrA binding to the operon promoter. We also demonstrate that FlhG, an accessory protein for flagellum synthesis, antagonized FlrA repression of the expression of the bpfA operon. Collectively, this work demonstrates that FlrA acts as a central mediator in the signaling pathway from c-di-GMP to BpfA-associated biofilm formation in S. putrefaciens CN32. IMPORTANCE Motility and biofilm are mutually exclusive lifestyles, shifts between which are under the strict regulation of bacteria attempting to adapt to the fluctuation of diverse environmental conditions. The FlrA protein in many bacteria is known to control motility as a master regulator of flagellum synthesis. This work elucidates its effect on biofilm formation by controlling the expression of the adhesin BpfA in S. putrefaciens CN32 in response to c-di-GMP. Therefore, FlrA plays a dual role in controlling motility and biofilm formation in S. putrefaciens CN32. The cooccurrence of flrA , bpfA , and the FlrA box in the promoter region of the bpfA operon in diverse Shewanella strains suggests that bpfA is a common mechanism that controls biofilm formation in this bacterial species.

The aim of the present study was to investigate whether breast cancer patients with changes from positive to negative in the hormone receptor following neoadjuvant chemotherapy (NAC) could benefit from adjuvant endocrine therapy (ET). Between December 2000 and November 2010, 97 eligible patients with a positive-to-negative switch of the hormone receptor status following NAC were identified. All the patients were categorized into two groups on the basis of the administration of ET: 57 ET-administered and 40 ET-naïve patients. Survival analyses were performed to examine the prognostic value of ET administration, as well as other clinical and pathological variables. The administration of ET was associated with a significantly improved disease-free survival (DFS) (P=0.018) in patients with a positive-to-negative switch of the hormone receptor status. The 5-year DFS rates were 77.0 and 55.5% in ET-administered and ET-naïve patients, respectively. The 5-year overall survival (OS) rate for ET-administered was also higher than that of the ET-naïve patients (81.3 vs. 72.7%, P=0.053), but the difference between the two groups did not reach a statistical significance. The present study revealed that patients with the hormone receptor that was altered from positive to negative following NAC benefit from ET, and the hormone receptor status should be evaluated not only in specimens obtained during post-NAC surgery, but also in specimens biopsied prior to NAC.

The sleeve regulating valve is widely used in the pipeline systems of process industries to control fluid flow. When flowing through the sleeve regulating valve, the water is easy to reach cavitation because of the pressure drop in the partial region, which may cause serious damage to pipeline system. In this paper, the pressure drop and cavitation characteristics in the sleeve regulating valve for different pressure differences and valve core displacements are investigated using a multiphase cavitation model. The pressure drop, velocity and vapor volume distribution in the regulating valves are obtained and analyzed. The total vapor volumes are also predicted and compared. The results show that the decrease of the valve core displacement induces the enlargement of the vapor distribution region and the increase of the vapor density. The increase of the pressure difference induces a more serious cavitation. The pressure difference has a slight influence on the cavitation intensity and density in the regulating valve when the valve core displacement is 60 mm. With the decrease of the valve core displacement, the effects of the pressure difference on the cavitation intensity are enhanced. This work is of significance for the cavitation control of the sleeve regulating valves.

Objective To investigate the predictive and prognostic value of topoisomerase IIα (Topo IIα, Topo II) expression in the primary tumors and residual tumors of local advanced breast cancer (LABC) patients being treated with anthracycline-based neoadjuvant chemotherapy (NCT). Methods The data from 283 LABC patients who had been treated with anthracycline-based neoadjuvant chemotherapy were collected. The expression of Topo IIα, HER-2 and other biomarkers was determined via immunohistochemical analysis in pre- and post-chemotherapy specimens. The status of pre-treatment biomarkers was correlated with the clinical response determined by the RECIST 1.1 criteria, whereas the post-treatment biomarkers were studied for prognostic value using the Cox model. Results By analyzing the complete data from 99 patients, the co-expression of HER-2/Topo IIα was found to be significantly correlated with the clinical response to chemotherapy (Logistic regression P = 0.042). Notably, a 20% alteration in the Topo IIα status during neoadjuvant chemotherapy was found, which could also influence the sensitivity to treatment. With a survival analysis performed in 245 patients with residual tumors after NCT, node metastasis, HER-2 and Ki-67 were independent predictors of patient outcome. However, post-treatment Topo IIα expression demonstrated significant prognostic value in HER-2+ patients ( P = 0.002). A relatively lower disease-free survival and overall survival was observed in HER-2+/Topo- patients (log rank P = 0.010 for DFS and P Conclusion Topo IIα, together with HER-2, might help to select for patients who could benefit from anthracycline-based neoadjuvant chemotherapy and identify non-complete responders at a higher risk of disease recurrence or death.

Chip morphology plays a predominant role in determining machinability and tool wear during the machining of titanium alloys. Chip formation process in prestressed cutting of titanium alloy TC4 was numerically explored via the finite element method. Crack initiation during the chip segmentation was realized by using a ductile fracture criterion which based on the strain energy. Effect of prestress on cutting force and chip formation as well as Mises stress distributions were revealed. The results indicate that chips show the similar characteristic of continuous and regular serrated shape, which is not affected by prestress. Initial stress distribution of workpiece was changed by prestress, which correspondingly leads to the alteration of stress distribution in the subsurface layer. The generated cutting force curves share the same average amplitude and analogous rhythm, which correspond to the chip forming process respectively.

Cis-stilbene combretastatin A-4 (CA-4) and a large group of its derivant compounds have been shown significant anti-angiogenesis activity. However the side effects even the toxicities of these chemicals were not evaluated adequately. The zebrafish model has become an important vertebrate model for evaluating drug effects. The testing of CA-4 on zebrafish is so far lacking and assessment of CA-4 on this model will provide with new insights of understanding the function of CA-4 on angiogenesis, the toxicities and side effects of CA-4. We discovered that 7–9 ng/ml CA-4 treatments resulted in developmental retardation and morphological malformation, and led to potent angiogenic defects in zebrafish embryos. Next, we demonstrated that intraperitoneal injection of 5, 10 and 20 mg/kg CA-4 obviously inhibited vessel plexus formation in regenerated pectoral fins of adult zebrafish. Interestingly, we proved that CA-4 treatment induced significant cell apoptosis in central nervous system of zebrafish embryos and adults. Furthermore, it was demonstrated that the neuronal apoptosis induced by CA-4 treatment was alleviated in p53 mutants. In addition, notch1a was up-regulated in CA-4 treated embryos, and inhibition of Notch signaling by DAPT partially rescued the apoptosis in zebrafish central nervous system caused by CA-4.

Logging measurement is the comprehensive reflection of solid particles and liquids in formation. Low energy sedimentary environment with weak water power and high salinity of formation water are the main requirements of low-resistance oil layer development. Whereas part of formation penetrated by hydrocarbon migration, which shows larger bend degrees of conductive tunnels in formation and higher resistivity measurement due to the oxidization of the residual crude oil, forms high-resistance water layer. Because of the complexity of accumulation conditions, these two difficult reservoirs exist in Putaohua reservoir of Weixing oilfield widely. Using geological characteristic parameters, such as, the distance of wells and scale faults, the formation structural location, resistivity measurement, sedimentary microfacies,thickness and porosity conditions, to evaluate oil and water property of the two difficult reservoirs, good results have been obtained.

Trichloroethylene (TCE), as one of the most common chlorinated organic compounds in soils and aquifers at many industrial sites, is carcinogenic and often recalcitrant in environment. TCE degradation in artificially contaminated soil samples was conducted using Fenton-like processes, i.e. , by addition of excess hydrogen peroxide (H 2 O 2 ). H 2 O 2 could directly oxidize TCE without addition of ferrous iron in contaminated soil. Under the optimal condition (H 2 O 2 concentration of 300 mg kg −1 , pH at 5.0, and reaction time of 30 min), the removal efficiency of TCE in the soil was up to 92.3%. When the initial TCE concentration increased from 30 to 480 mg kg −1 in soil, the TCE removal rates varied from 89.2% to 86.6%; while the residual TCE in soil ranged from 2.28 to 47.57 mg kg −1 . Results from successive oxidations showed that the TCE removal rate with the TCE concentration of 180 mg kg −1 increased slightly from 91.6% to 96.2% as the number of successive oxidation cycle increased from one to four. Therefore, increasing the frequency of H 2 O 2 oxidation was perhaps a feasible way to increase TCE removal rate for TCE-contaminated soil.