Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vγ9Vδ2 T cells.

In both cancer and infections, diseased cells are presented to human Vγ9Vδ2 T cells through an 'inside out' signalling process whereby structurally diverse phosphoantigen (pAg) molecules are sensed by the intracellular domain of butyrophilin BTN3A11-4. Here we show how-in both humans and alpaca-multiple pAgs function as 'molecular glues' to promote heteromeric association between the intracellular domains of BTN3A1 and the structurally similar butyrophilin BTN2A1. X-ray crystallography studies visualized that engagement of BTN3A1 with pAgs forms a composite interface for direct binding to BTN2A1, with various pAg molecules each positioned at the centre of the interface and gluing the butyrophilins with distinct affinities. Our structural insights guided mutagenesis experiments that led to disruption of the intracellular BTN3A1-BTN2A1 association, abolishing pAg-mediated Vγ9Vδ2 T cell activation. Analyses using structure-based molecular-dynamics simulations, 19F-NMR investigations, chimeric receptor engineering and direct measurement of intercellular binding force revealed how pAg-mediated BTN2A1 association drives BTN3A1 intracellular fluctuations outwards in a thermodynamically favourable manner, thereby enabling BTN3A1 to push off from the BTN2A1 ectodomain to initiate T cell receptor-mediated γδ T cell activation. Practically, we harnessed the molecular-glue model for immunotherapeutics design, demonstrating chemical principles for developing both small-molecule activators and inhibitors of human γδ T cell function.

Ultrafast polarization characterization with Mueller matrix based on optical time-stretch and spectral encoding.

High-speed optical polarization characterization is highly desirable for a wide range of applications, including remote sensing, telecommunication, and medical diagnosis. The utilization of the Mueller matrix provides a superior systematic and comprehensive approach to represent polarization attributes when matter interacts with optical beams. However, the current measurement speed of Mueller matrix is limited to only seconds or milliseconds. In this study, we present an ultrafast Mueller matrix polarimetry (MMP) technique based on optical time-stretch and spectral encoding that enables us to achieve an impressive temporal resolution of 4.83 nanoseconds for accurate Mueller matrix measurements. The unique feature of optical time-stretch technology enables continuous, ultrafast single-shot spectroscopy, resulting in a remarkable speed of up to 207 MHz for spectral encoding Mueller matrix measurement. We have employed an effective Mueller linear reconstruction algorithm based on the measured modulation matrix, accounting for all potential non-ideal effects of polarization components like retardance error and azimuth error. To ensure high precision, prior to the actual measurement, high-order dispersion induced by time-stretch requires adjustment through proper modulation matrix design. Upon such correction, both the results of static and rapid dynamic samples measurements exhibit exceptional accuracy with root-mean-square error (RMSE) approximately equal to 0.04 and 0.07 respectively. This presented ultrafast MMP provides a significant advance over preceding endeavors, enabling superior accuracy and increased speed concurrently.

Modified Y-V plasty based on MRU evaluation for iatrogenic bladder outlet obliteration: a multicentre experience in China.

PURPOSE: To compare the diagnostic ability of traditional radiographic urethrography and magnetic resonance urethrography (MRU) for iatrogenic bladder outlet obliteration (BOO), and explore the efficacy and complications of laparoscopic modified Y-V plasty for patients selected based on MRU evaluation. METHODS: 31 patients with obliteration segments ≤ 2 cm and no false passages or diverticula based on MRU evaluation from eight centers in China were included. Obliteration segments were measured preoperatively by MRU and conventional RUG/VCUG and compared with intra-operative measurements. Surgical effects were evaluated by uroflow rates, urethrography, or cystoscopy at 1, 3, 6, and 12 months post-operation and then every 12 months. Postoperative urinary continence was assessed by 24-h urine leakage (g/day). RESULTS: The results showed that MRU measured the length of obliteration more accurately than RUG/VCUG (MRU 0.91 ± 0.23 cm, RUG/VCUG 1.72 ± 1.08 cm, Actual length 0.96 ± 0.36 cm, p < 0.001), and clearly detected false passages and diverticula. Laparoscopic Y-V plasty was modified by incisions at 5 and 7 o'clock positions and double-layer suture with barbed sutures. All operations were successfully completed within a median time of 75 (62-192) minutes and without any complications. Urethral patency and urinary continence rates were 90.3% (28/31) and 87.1% (27/31), respectively. Three recurrences were cured by direct visual internal urethrotomy. Four patients had stress urinary incontinence after catheter removal 14 days post-operation, with urine leakage of 80-120 g/day, not relieved during follow-up. CONCLUSIONS: Laparoscopic modified Y-V plasty based on MRU evaluation is a promising approach for iatrogenic BOO, with a high patency rate and a low incontinence rate.

Urethral-sparing laparoscopic simple prostatectomy for the treatment of benign prostatic hyperplasia with asymptomatic urethral stricture after urethral stricture surgery.

OBJECTIVE: To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery. METHODS: We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months. RESULTS: All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100-145). Median estimated blood loss was 224 ml (IQR: 190-255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P < 0.05). A total of 25 patients had normal ejaculation preoperatively and 3 patients (12%) complained retrograde ejaculation postoperatively. Two patients (5.1%) reported stress urinary incontinence (SUI) and no patient reported aggravated urethral stricture during follow-up. CONCLUSIONS: US-LSP was safe and effective in treating large-volume BPH with asymptomatic urethral stricture after urethral stricture surgery. Meanwhile, US-LSP could reduce the risk of SUI in patients with asymptomatic posterior urethral stricture and maintain ejaculatory function in a high percentage of patients.

Model containing sarcopenia and visceral adiposity can better predict the prognosis of hepatocellular carcinoma: a multicenter study.

AIM: This study aimed to explore whether the addition of sarcopenia and visceral adiposity could improve the accuracy of model predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC). METHODS: In total, 394 patients with HCC from five hospitals were divided into the training and external validation datasets. Patients were initially treated by liver resection or transarterial chemoembolization. We evaluated adipose and skeletal muscle using preoperative computed tomography imaging and then constructed three predictive models, including metabolic (ModelMA), clinical-imaging (ModelCI), and combined (ModelMA-CI) models. Their discrimination, calibration, and decision curves were compared, to identify the best model. Nomogram and subgroup analysis was performed for the best model. RESULTS: ModelMA-CI containing sarcopenia and visceral adiposity had good discrimination and calibrations (integrate area under the curve for PFS was 0.708 in the training dataset and 0.706 in the validation dataset). ModelMA-CI had better accuracy than ModelCI and ModelMA. The performance of ModelMA-CI was not affected by treatments or disease stages. The high-risk subgroup (scored > 198) had a significantly shorter PFS (p < 0.001) and poorer OS (p < 0.001). CONCLUSIONS: The addition of sarcopenia and visceral adiposity improved accuracy in predicting PFS in HCC, which may provide additional insights in prognosis for HCC in subsequent studies.

Double C-Arm Digital Subtraction Angiography Guidance During Transjugular Intrahepatic Portosystemic Shunt Placement.

BACKGROUND This study aimed to evaluate the safety and efficacy of portal vein puncture with a new guidance system using double C-arm digital subtraction angiography (DSA) during transjugular intrahepatic portosystemic shunt (TIPS) placement. MATERIAL AND METHODS The procedure details of TIPS placements performed on 39 patients in our center between January and December 2021 were retrospectively analyzed. The procedure was performed under double C-arm DSA guidance (study group) and C-arm DSA (control group) in 18 and 21 patients, respectively. We analyzed the procedure's technical success, duration of the overall procedure, portal vein puncture, fluoroscopy, radiation exposure, complications, and mortality and morbidity rates 30 days after the procedure. RESULTS TIPS placement was performed successfully in all patients. The mean portal vein puncture time in the study group (9±5.7 min) was significantly shorter than in the control group (33±14.9 min, p=0.02). The complete mean dose area product of the procedure showed no significant differences (study group, 126±53 Gy/cm²; control group. 142±66 Gy/cm²; p=0.42). The intraprocedural complication rates were 0% and 19% in the study and control groups, respectively (p=0.04). The 30-day post-procedural mortality rate in the control group was 4.8% (1/21), with no deaths from technical complications. CONCLUSIONS Double C-arm DSA guidance is a safe and effective method to assist TIPS placement. This approach may result in shorter portal vein puncture time and lower intraprocedural complication rates.

Standardized Tip-Apex Distance (STAD): a modified individualized measurement of cephalic fixator position based on its own femoral head diameter in geriatric intertrochanteric fractures with internal fixation.

OBJECTIVE: To design a standardized Tip-Apex Distance (STAD) and analyze the clinical significance of STAD in predicting cut-out in geriatric intertrochanteric fractures with internal fixation. METHODS: Firstly, we designed STAD according to the rule of TAD. We measured the STAD individually based on its own femoral head diameter (iFHD) instead of the known diameter of the lag screw in calculating TAD, resulting in that the STAD is simply the relative quantitation relationship of iFHD (the times of iFHD). In this study, we assumed that all the iFHD was 6D (1iFHD = 6D, or 1D = 1/6 of iFHD) in order for complete match of the Cleveland zone system, easy comparison of the STAD, and convenient identification for artificial intelligence. Secondly, we calculated and recorded all the STAD of cephalic fixator in 123 eligible ITF patients. Thirdly, we grouped all the ITF patients into the Failure and Non-failure groups according to whether cut-out or not, and analyzed the correlation between the cut-out and the STAD. RESULTS: Cleveland zone, Parker's ratio (AP), TAD, and STAD were associated with the cut-out in univariate analysis. However, only STAD was the independent predictor of the cut-out by multivariate analysis. No cut-out was observed when STAD ≤ 2D (1/3 of iFHD). The Receiver Operating Characteristic (ROC) curve indicated that STAD was a reliable predictor of cut-out, and the best cut-off value of STAD was 2.92D. Cut-out rate increased dramatically when STAD increased, especially when STAD > 3D (1/2 of iFHD). CONCLUSION: Essentially, the STAD is a relative quantitation relationship of iFHD. The STAD is a reliable measurement of cephalic fixator position in predicting cut-out in geriatric ITF patients with single-screw cephalomedullary nail fixations. For avoiding cut-out, the STAD should be no more than a half of iFHD. LEVEL OF EVIDENCE: Level III, Prognostic Study.

A systematic review of endovenous ablation for the treatment of small saphenous varicose veins.

Insufficiency of the small saphenous vein causes 15% of varicose veins in the lower extremities. Endovenous ablation for the treatment of small saphenous vein varices has become a trend, and an increasing number of studies have reported the effects of different types of endovenous ablation in patients with small saphenous varicose veins. The purpose of this systematic review is to summarize the results of existing studies on endovenous ablation for the treatment of small saphenous varicose veins, compare its role and efficacy, and provide insights into the future development of endovenous ablation for treating small saphenous varicose veins. A systematic review of literature published from January 1, 2002 to January 1, 2022 was conducted from PubMed, Embase, and China Academic Journals full-text databases. The pre-determined inclusion criteria were clinical literature of endovenous ablation for treating small saphenous varicose veins. Keywords included "ablation", "small saphenous vein", "lesser saphenous vein", "short saphenous vein", "xiaoyinjingmai" and "xiaorong". Of the 506 articles screened, 33 articles were included in this review: 19 articles were related to endovenous laser ablation, five were related to mechanochemical ablation, seven were related to radiofrequency ablation, and two were related to both endovenous laser ablation and radiofrequency ablation. The anatomical success rate of endovenous laser ablation, radiofrequency ablation, and mechanochemical ablation were 94.3%, 96.0%, and 88.1%, respectively, and the heterogeneities were all moderate. Most of the current studies are of a low-quality level of research. Hence, long-term follow-up studies and large-scale randomized controlled trials are required to obtain high-quality evidence. Although the gold standard for the treatment of small saphenous vein insufficiency remains unclear, endovenous ablation is still the recommended method.

Structural insights revealed by crystal structure of B38-CAP, an isoenzyme of carboxypeptidase ACE2, the receptor of SARS-CoV-2.

The worldwide pandemic of Coronavirus disease 2019 (COVID-19) is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and further worsened by the emergence of a variety of SARS-CoV-2 variants. Angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase of M32 family, serves as the receptor of SARS-CoV-2 and key regulator of host renin-angiotensin system (RAS), both of which are mainly mediated via the carboxypeptidase domain of ACE2 (sACE2) or its activity. sACE2 is thus promising in the treatment of COVID-19 but unfortunately weakened by its unstrigent substrate preference and complex interplay with host RAS. B38-CAP, an isoenzyme of ACE2, partically compensates these defects but still encounters the problem related to carboxypeptidase activity and specificity. In this study, we firstly determined the crystal structure of B38-CAP at a resolution of 2.44 Å which exists in dimeric form with the non-crystallographic two-fold axis being in coincidence with the crystallographic two-fold axis. Further structural analysis revealed the structural conservatism feature among M32 family, particularly the catalytic core and moreover lead us to hypothesize that conformational flexibility might play an pivotal role in the catalysis of B38-CAP and ACE2. The work provided here presents key features of the M32 family carboxypeptidase and provides structural basis for further development of B38-CAP-based anti-SARS-CoV-2 drugs.

Mapping Techniques for the Design of Lithium-Sulfur Batteries.

Mapping technique has been the powerful tool for the design of next-generation energy storage devices. Unlike the traditional ion-insertion based lithium batteries, the Li-S battery is based on the complex conversion reactions, which require more cooperation from mapping techniques to elucidate the underlying mechanism. Therefore, in this review, the representative works of mapping techniques for Li-S batteries are summarized, and categorized into the studies of lithium metal anode and sulfur cathode, with sub-sections based on shared characterization mechanisms. Due to specific features of mapping techniques, various aspects such as compositional distribution, in-plain/cross section characterization, coin cell/pouch cell configuration, and structural/mechanical analysis are emphasized in each study, aiming for the guidance for developing strategies to improve the battery performances. Benefited from the achieved progresses, suggestions for future studies based on mapping techniques are proposed to accelerate the development and commercialization of the Li-S battery.

Structural and Functional Insights into a Nonheme Iron- and α-Ketoglutarate-Dependent Halogenase That Catalyzes Chlorination of Nucleotide Substrates.

Nonheme iron- and α-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C(sp3)-H bonds, exhibit tremendous potential in the challenging asymmetric halogenation. AdeV from Actinomadura sp. ATCC 39365 is the first identified carrier protein-free NHFeHal that catalyzes the chlorination of nucleotide 2'-deoxyadenosine-5'-monophosphate (2'-dAMP) to afford 2'-chloro-2'-deoxyadenosine-5'-monophosphate. Here, we determined the complex crystal structures of AdeV/FeII/Cl and AdeV/FeII/Cl/αKG at resolutions of 1.76 and 1.74 Å, respectively. AdeV possesses a typical ß-sandwich topology with H194, H252, αKG, chloride, and one water molecule coordinating FeII in the active site. Molecular docking, mutagenesis, and biochemical analyses reveal that the hydrophobic interactions and hydrogen bond network between the substrate-binding pocket and the adenine, deoxyribose, and phosphate moieties of 2'-dAMP are essential for substrate recognition. Residues H111, R177, and H192 might play important roles in the second-sphere interactions that control reaction partitioning. This study provides valuable insights into the catalytic selectivity of AdeV and will facilitate the rational engineering of AdeV and other NHFeHals for synthesis of halogenated nucleotides. IMPORTANCE Halogenated nucleotides are a group of important antibiotics and are clinically used as antiviral and anticancer drugs. AdeV is the first carrier protein-independent nonheme iron- and α-ketoglutarate (αKG)-dependent halogenase (NHFeHal) that can selectively halogenate nucleotides and exhibits restricted substrate specificity toward several 2'-dAMP analogues. Here, we determined the complex crystal structures of AdeV/FeII/Cl and AdeV/FeII/Cl/αKG. Molecular docking, mutagenesis, and biochemical analyses provide important insights into the catalytic selectivity of AdeV. This study will facilitate the rational engineering of AdeV and other carrier protein-independent NHFeHals for synthesis of halogenated nucleotides.

Ultrafast Mueller matrix polarimetry with 10 nanosecond temporal resolution based on optical time-stretch.

A fastest full Mueller matrix polarimeter, to the best of our knowledge, based on optical time-stretch has been proposed and demonstrated. Thanks to the time-stretch-based ultrafast spectra detection mechanism, its measurement time could reach 10 ns. Additionally, a novel, to the best of aour knowledge, simpler method to estimate its main systematic error has been proposed and verified. With the proposed method, static measurement of polarizer and wave plate is executed with a maximum coefficient error of below 0.1. Dynamic measurement of a free space electro-optic modulator as fast-changing phase retardation has also been executed to demonstrate the feasibility of the proposed system.

Occurrence and Transformation of Ephedrine/Pseudoephedrine and Methcathinone in Wastewater in China.

Previous wastewater-based epidemiology studies on methcathinone (MC), a controlled substance in many countries, attributed its occurrence in wastewater to its misuse. However, such attribution did not consider the possibility that MC may also come from the transformation of ephedrine (EPH) and pseudo-ephedrine (PEPH). In this work, EPH/PEPH and MC in wastewater of six major Chinese cities were systematically examined. EPH/PEPH concentrations in all the cities showed clear seasonal variations, with maximum and minimum concentrations observed in winter and summer, respectively. In contrast, MC concentrations were the lowest in winter, leading to minimum concentration ratios between MC and EPH/PEPH in winter. Lack of MC seizure in the cities suggests that MC abuse could not account for the ubiquitous detection of the substance in the wastewater of these cities. Batch experiments confirmed EPH/PEPH transformation into MC in wastewater. The significantly lower transformation rate at a lower temperature was consistent with low MC concentrations in winter. These results indicate that when monitoring MC through wastewater, EPH/PEPH concentrations must be determined simultaneously to avoid false identification of MC abuse. The observed ratios of MC to EPH/PEPH concentrations in this work may be used to determine MC abuse. Alternatively, other biomarkers (e.g., cathinone) may be considered to avoid interference from EPH/PEPH transformation.

Risk factors for cut-outs in geriatric intertrochanteric fractures with cephalomedullary nailing after obtaining acceptable reduction: a case-control study.

BACKGROUND: It is irresponsible if we disregard reduction quality to talk about cut-outs in intertrochanteric fractures (ITF) with internal fixation. The aim of this study is to analyze the risk-factors for cut-outs in geriatric ITF with cephalomedullary nailing after obtaining acceptable reduction. METHODS: In order to investigate the risk-factors for cut-outs in geriatric ITF after obtaining acceptable reduction, we retrospectively reviewed 367 patients who underwent cephalomedullary nail for ITF in our department between September 2016 and December 2021. Potential variables including demographic data and radiological parameters (namely the fracture type, Singh index, lateral wall fracture, cephalic nail position, Parker's ratio index, tip-apex-distance (TAD), and calcar-referenced TAD (CalTAD)) were collected. Logistic regression analysis was performed to identify the significant risk factors for cut-outs. RESULTS: One hundred twenty-one patients were suitable for this study. Of the 121 cases, nine cases (7.4%) were observed with cut-out or pending cut-out. We found that Age (adjusted odds ratio (OR) 1.158, 95% confidence interval (CI) 1.016 to 1.318, p = 0.028), lateral wall fracture (adjusted OR 11.07, 95%CI 1.790 to 68.380, p = 0.01), and CalTAD (adjusted OR 1.277, 95%CI 1.005 to 1.622, p = 0.045) were independent risk-factors for cut-outs. CONCLUSIONS: Age, lateral wall fracture and CalTAD are independent risk-factors for cut-outs in geriatric ITF with cephalomedullary nailing after obtaining acceptable reduction. In order to avoid cut-outs, an optimal CalTAD is necessary even obtaining acceptable reduction, especially in the over-aged patients with lateral wall fracture.

Structural investigation of a thermostable 1,2-ß-mannobiose phosphorylase from Thermoanaerobacter sp. X-514.

1,2-ß-Mannobiose phosphorylases (1,2-ß-MBPs) from glycoside hydrolase 130 (GH130) family are important bio-catalysts in glycochemistry applications owing to their ability in synthesizing oligomannans. Here, we report the crystal structure of a thermostable 1,2-ß-MBP from Thermoanaerobacter sp. X-514 termed Teth514_1789 to reveal the molecular basis of its higher thermostability and mechanism of action. We also solved the enzyme complexes of mannose, mannose-1-phosphate (M1P) and 1,4-ß-mannobiose to manifest the enzyme-substrate interaction networks of three main subsites. Notably, a Zn ion that should be derived from crystallization buffer was found in the active site and coordinates the phosphate moiety of M1P. Nonetheless, this Zn-coordination should reflect an inhibitory status as supplementing Zn severely impairs the enzyme activity. These results indicate that the effects of metal ions should be taken into consideration when applying Teth514_1789 and other related enzymes. Based on the structure, a reliable model of Teth514_1788 that shares 61.7% sequence identity to Teth514_1789 but displays a different substrate preference was built. Analyzing the structural features of these two closely related enzymes, we hypothesized that the length of a loop fragment that covers the entrance of the catalytic center might regulate the substrate selectivity. In conclusion, these information provide in-depth understanding of GH130 1,2-ß-MBPs and should serve as an important guidance for enzyme engineering for further applications.

Structural dissection of unnatural ginsenoside-biosynthetic UDP-glycosyltransferase Bs-YjiC from Bacillus subtilis for substrate promiscuity.

Glycosylation catalyzed by uridine diphosphate-dependent glycosyltransferases (UGT) contributes to the chemical and functional diversity of a number of natural products. Bacillus subtilis Bs-YjiC is a robust and versatile UGT that holds potentials in the biosynthesis of unnatural bioactive ginsenosides. To understand the molecular mechanism underlying the substrate promiscuity of Bs-YjiC, we solved crystal structures of Bs-YjiC and its binary complex with uridine diphosphate (UDP) at resolution of 2.18 Å and 2.44 Å, respectively. Bs-YjiC adopts the classical GT-B fold containing the N-terminal and C-terminal domains that accommodate the sugar acceptor and UDP-glucose, respectively. Molecular docking indicates that the spacious sugar-acceptor binding pocket of Bs-YjiC might be responsible for its broad substrate spectrum and unique glycosylation patterns toward protopanaxadiol-(PPD) and PPD-type ginsenosides. Our study reveals the structural basis for the aglycone promiscuity of Bs-YjiC and will facilitate the protein engineering of Bs-YjiC to synthesize novel bioactive glycosylated compounds.

Ion-Inserted Metal-Organic Frameworks Accelerate the Mass Transfer Kinetics in Lithium-Sulfur Batteries.

Lithium-sulfur battery promises great potential to promote the reform of energy storage field. Modified functional interlayer on separator has been recognized as efficient method to promote battery performances, mainly focusing on the entrapment and catalytic effect toward lithium polysulfide, while the mass transfer property across the interlayers has not been carefully considered. Herein, a dense layer composed of ion-inserted metal-organic frameworks is used to facilitate mass transfer across the layer and ensure high polysulfides entrapment efficiency. In situ Raman study reveals that the dense functional layer blocks the transfer of Li ions, while the ion-inserted layer can accelerate the ion-transfer kinetics and avoid the ion depletion caused polarization. As a result, a specific capacity of 742 mAh g-1 is obtained at 2 C, with the decay rate of 0.089% per cycle at 1 C over 600 cycles, demonstrating great potential for the application in advanced Li-S batteries.

TRIM37 overexpression is associated with chemoresistance in hepatocellular carcinoma via activating the AKT signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the worldwide. Sorafenib is approved for first-line therapy against advanced HCC, but chemo-resistance is still a leading cause of tumor relapse and treatment failure in HCC. Thus, there is a significant clinical need to identify effective strategies to overcome drug resistance on the disease. METHODS: The protein and mRNA expression of TRIM37 in HCC cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. HCC tissue samples were analyzed by IHC to investigate the association between TRIM37expression and the clinicopathological characteristics of HCC patients. Functional assays, such as MTT, FACS, and Tunel assay, are used to determine the oncogenic role of TRIM37 in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37promotes chemoresistance in HCC. RESULTS: We found that both the mRNA and protein expression of TRIM37 was markedly upregulated in HCC cell lines and tissues, especially in Sorafenib-resistance HCC tissues. Moreover, high TRIM37 expression was associated with poor prognosis with HCC patients. TRIM37 overexpression confers Sorafenib resistance on HCC cells; however, inhibition of TRIM37 sensitized HCC cell lines to Sorafenib cytotoxicity. Additionally, TRIM37 upregulated the levels of AKT activity and phosphorylated AKT, thereby activating canonical AKT signaling. CONCLUSION: Our findings suggest that targeting TRIM37 signaling may represent a promising strategy to enhance Sorafenib response in HCC patients with chemoresistant.

Joint Salvage and Biological Repair of Massive-Cavity Bone Defects After Extensive Curettage of Campanacci Grade II or III Giant Cell Tumor Around the Knee With Vascularized Fibular Autograft and Cancellous Allograft.

OBJECTIVE: The aim of the study was to report the clinical outcomes of repair of massive-cavity bone defects after extensive curettage of Campanacci grade II or III giant cell tumor (GCT) around knee with vascularized fibular autograft and cancellous allograft. METHODS: There were 12 consecutive patients with Campanacci grade II or III GCT around knee treated in our department between 2004 and 2016. All the patients underwent clinical evaluation, plain radiography, and/or magnetic resonance imaging of the knee right after admission. To preserve their knee function, we repaired the massive-cavity bone defects after extensive curettage of GCT by vascularized fibular autografts and cancellous allograft. All the patients were evaluated through clinical examinations, plain radiography of the knee and chest, and Musculoskeletal Tumor Society (MSTS) scores of the lower extremity in the follow-ups. RESULTS: The follow-up ranged from 1.5 to 12.0 years (mean, 4.2 years). There were no local recurrences or lung metastasis in any of the 12 patients at the last follow-up. Ten patients had no pain or experienced occasional pain, and 9 were able to resume their previous work. The mean range of motion of knee flexion was 117 degrees, and the extension was -6 degrees. The mean MSTS score was 24.7, and a total of 10 patients had excellent or good MSTS scores. CONCLUSIONS: It is reliable to achieve knee joint salvage and repair massive-cavity bone defects after extensive curettage with vascularized fibular autograft and cancellous allograft in patients with Campanacci grade II or III GCT around the knee.

Repair of Small-Size Wound With Achilles Tendon Exposure With Proximal Pedicled Cutaneous Neurovascular Flap.

OBJECTIVE: To investigate the clinical outcomes associated with repairing of small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap in the dorsolateral foot. METHODS: After thorough debridement, 16 cases with small-sized wounds of Achilles tendon exposure were repaired by proximal pedicled cutaneous neurovascular flap of the dorsolateral foot, and their clinical outcomes were observed. RESULTS: All the flaps in the 16 cases survived completely, excluding the marginal part necrosis in 1 case, and all the wounds were healed. The 2-point discrimination of the flaps was 14.53 ± 1.55 mm (range, 12-17 mm) in patients without sural nerve injury after 3 to 18 months follow-up. No discomfort was felt in wearing normal shoes by all the 16 patients. CONCLUSIONS: It is reasonable to repair the small-sized wounds of Achilles tendon exposure with proximal pedicled cutaneous neurovascular flap of dorsolateral foot due to its effective repair of the wound, relatively uncomplicated surgery, and had satisfactory healing recovery.