Distal clavicle fractures treated by anteroinferior plating with a single screw: Two case reports.

BACKGROUND: For the treatment of distal clavicle fractures, each treatment method has its own advantages and disadvantages, and there is no optimal surgical solution. CASE SUMMARY: Based on this, we report 2 cases of distal clavicle fractures treated utilizing an anterior inferior plate with a single screw placed in the distal, in anticipation of providing a better surgical approach to distal clavicle fracture treatment. Two patients were admitted to the hospital after trauma with a diagnosis of distal clavicle fracture, and were admitted to the hospital for internal fixation of clavicle fracture by incision and reduction, with good postoperative functional recovery. CONCLUSION: With solid postoperative fixation and satisfactory prognostic functional recovery, this technique has been shown to be simple, easy to perform and effective.

Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.

OBJECTIVES: Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity. MATERIALS AND METHODS: This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods. RESULTS: The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases. CONCLUSIONS: EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.

Impact of Persistent Poor Sleep Quality on Post-Stroke Anxiety and Depression: A National Prospective Clinical Registry Study.

Purpose: The impact of poor sleep quality after stroke, especially persistent poor sleep quality, on poststroke anxiety and depression is unclear. We seek to investigate the impact of baseline and persistent poor sleep quality on short-term poststroke anxiety and depression. Patients and Methods: Data were analyzed for 1619 patients with acute ischemic stroke from the Impairment of Cognition and Sleep after Acute Ischemic Stroke or Transient Ischemic Attack in Chinese Patients study (ICONS). The sleep quality was assessed at 2 weeks and 3 months using the Pittsburgh Sleep Quality Index scale (PSQI). Poor sleep quality was defined as a PSQI score of >5, and persistent poor sleep quality was defined as a PSQI score of >5 at each time point. Patients were divided into three groups according to the quality of sleep: good sleep quality, baseline poor sleep quality and persistent poor sleep quality. Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 scale (GAD-7), and Modified Rankin Scale (mRS) at 3 months after stroke were taken as the study outcomes. Results: Persistent poor sleep quality was present in 70.2% of patients after stroke. Compared to those with good sleep quality, patients with baseline poor sleep quality did not show significant differences in disability, anxiety and depression. However, patients with persistent poor sleep were at increased risk of depression (odds ratio, OR 3.04, 95% confidence interval, CI 1.66-5.57, P < 0.01) and anxiety (OR 3.20, 95% CI 1.42-7.19, P < 0.01) at 3 months after stroke. Persistent poor sleep quality was not identified as a risk factor for functional disability at 3 months. Conclusion: Patients with persistent poor sleep quality are at added risks for depression and anxiety after stroke.

Prognosis and antiplatelet therapy of small single subcortical infarcts in penetrating artery territory: a post hoc analysis of the Third China National Stroke Registry.

Background: Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI. Methods: We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography. Results: Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p<0.0001) and 1 year (OR 2.054, 95% CI 1.561 to 2.702; p<0.0001), as well as composite vascular events at 3 months (OR 2.306, 95% CI 1.674 to 3.178; p<0.0001) and 1 year (OR 1.983, 95% CI 1.530 to 2.570; p<0.0001), compared with the non-PAS group. In both groups, dual antiplatelet therapy was not superior to single antiplatelet therapy in preventing stroke recurrence, composite vascular events and disability. Conclusion: PAS related to significantly higher rates of short-term and long-term stroke recurrence and composite vascular events, suggesting heterogeneous mechanisms in SSSI subgroups. The effectiveness of antiplatelet therapy for SSSI needs further investigation.

Brass wires with different surface wettability used for in-tube solid-phase microextraction.

Metal wires have been widely used as substrates for solid-phase microextraction (SPME) fibers instead of commonly fragile silica fibers, but complicated coating modification of their surface is required. Herein, a series of brass wires were soaked in an acidic iron trichloride solution with ultrasonication, which etched the brass surface through a redox reaction. The surface wettability of the pristine brass wire was transformed from hydrophobic to hydrophilic owing to the formation of micro/nanoscale hierarchical structures. After modification with n-octadecanethiol (ODT) and 2-naphthalenethiol (NT), respectively, both wires exhibited superhydrophobicity. Characterization of the resulting wires was conducted using SEM and EDS, and the surface wettability was measured by a contact angle goniometer using identical brass meshes. To build an in-tube SPME-high-performance liquid chromatography (HPLC) online system, the extraction tube was connected with HPLC equipment by replacing the sample loop of a six-port valve. Four types of wires, including the pristine hydrophobic brass wire, the hydrophilic wire after chemical etching, and both superhydrophobic wires, were comparatively applied to the extraction of six estrogens. The optimized extraction conditions were a sample volume of 60 mL, an injection rate of 2 mL/min, and a desorption time of 2 min at a flow rate of 1 mL/min. The results showed that the highest estrogen extraction efficiency was obtained using the superhydrophobic wire modified by NT, with the enrichment factors in the range of 36-350. Furthermore, the superhydrophobic NT wire exhibited a higher extraction efficiency than the ODT wire with identical superhydrophobicity. This demonstrated that the higher extraction efficiency was mainly dependent on  π-π interactions between the sorbent containing naphthalene rings and the target compounds containing benzene rings, rather than surface wettability.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer.

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Genomic Landscapes of Epstein-Barr Virus in Pulmonary Lymphoepithelioma-Like Carcinoma.

Epstein-Barr virus (EBV) infection is associated with multiple malignancies, including pulmonary lymphoepithelioma-like carcinoma (pLELC), a particular subtype of primary lung cancer. However, the genomic characteristics of EBV related to pLELC remain unclear. Here, we obtained the whole-genome data set of EBV isolated from 78 pLELC patients and 37 healthy controls using EBV-captured sequencing. Compared with the reference genome (NC_007605), a total of 3,995 variations were detected across pLELC-derived EBV sequences, with the mutational hot spots located in latent genes. Combined with 180 published EBV sequences derived from healthy people in Southern China, we performed a genome-wide association study and identified 32 variations significantly related to pLELC (P < 2.56 × 10-05, Bonferroni correction), with the top signal of single nucleotide polymorphism (SNP) coordinate T7327C (OR = 1.22, P = 2.39 × 10-15) locating in the origin of plasmid replication (OriP). The results of population structure analysis of EBV isolates in East Asian showed the EBV strains derived from pLELC were more similar to those from nasopharyngeal carcinoma (NPC) than other EBV-associated diseases. In addition, typical latency type-II infection were recognized for EBV of pLELC at both transcription and methylation levels. Taken together, we defined the global view of EBV genomic profiles in pLELC patients for the first time, providing new insights to deepening our understanding of this rare EBV-associated primary lung carcinoma. IMPORTANCE Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare, distinctive subtype of primary lung cancer closely associated with Epstein-Barr virus (EBV) infection. Here, we gave the first overview of pLELC-derived EBV at the level of genome, methylation and transcription. We obtained the EBV sequences data set from 78 primary pLELC patients, and revealed the sequences diversity across EBV genome and detected variability in known immune epitopes. Genome-wide association analysis combining 217 healthy controls identifies significant variations related to the risk of pLELC. Meanwhile, we characterized the integration landscapes of EBV at the genome-wide level. These results provided new insight for understanding EBV's role in pLELC tumorigenesis.

Efficacy of cathodal transcranial direct current stimulation on electroencephalographic functional networks in patients with focal epilepsy: Preliminary findings.

BACKGROUND: Neuromodulation is a promising therapeutic alternative for epilepsy. We aimed to explore the efficacy and safety of cathodal transcranial current direct stimulation (ctDCS) on electroencephalographic functional networks in focal epilepsy. METHODS: A sham-controlled, double-blinded, randomized study was conducted on 25 participants with focal epilepsy who underwent a 5-day, -1.0 mA, 20 min ctDCS, which targeted at the most active interictal epileptiform discharge (IED) region. We examined the electroencephalograms (EEGs) at baseline, immediately and at 4 weeks following ctDCS. The graph theory-based brain networks were established through time-variant partial directed coherence (TVPDC), and were calculated between each pair of EEG signals. The functional networks were characterized using average clustering coefficient, characteristic path length, and small-worldness index. The seizure frequencies, IEDs, graph-theory metrics and cognitive tests were compared. RESULTS: Preliminary findings indicated an IED reduction of 30.2% at the end of 5-day active ctDCS compared to baseline (p < 0.10) and a significant IED reduction of 33.4% 4 weeks later (p < 0.05). In terms of the EEG functional network, the small-worldness index significantly reduced by 3.5% (p < 0.05) and the characteristic path length increased by 1.8% (p < 0.10) at the end of the session compared to the baseline. No obvious change was found in the seizure frequency during follow-up (p > 0.05). The Mini-Mental State Examination (MMSE) showed no difference between the active and sham groups (p > 0.05). No severe adverse reactions were observed. CONCLUSIONS: In focal epilepsy, the 5-day consecutive ctDCS may potentially decrease the IEDs and ameliorate the EEG functional network, proposing a novel personalized therapeutic scenario for epilepsy.

Is Early Controlled Motion and Weightbearing Recommended for Nonoperatively Treated Acute Achilles Tendon Rupture? A Systematic Review and Meta-analysis.

BACKGROUND: There is disagreement as to whether early controlled motion and weightbearing confer a beneficial effect for nonoperatively treated acute Achilles tendon rupture (ATR) compared with immobilization and late weightbearing. PURPOSE: To conduct a meta-analysis of randomized controlled trials (RCTs) to determine whether early controlled motion and weightbearing results in different outcomes compared with immobilization and late weightbearing for nonoperatively treated patients with acute ATR. STUDY DESIGN: Systematic review; Level of evidence, 1. METHODS: We conducted a search in the PubMed, Web of Science, and EMBASE databases for relevant RCTs in humans from January 1981 to August 2020. The primary outcome was the Achilles Tendon Total Rupture Score (ATRS) at 1-year follow-up. The secondary outcomes were the rerupture rate, return to sports activity and work, and the heel-rise work (limb symmetry index [LSI]). Study quality was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Included were 7 RCTs involving 424 participants (n = 215 treated with early controlled motion and weightbearing [early group], n = 209 treated with immobilization and late weightbearing [late group]). The quality assessment indicated a low risk of bias in all included RCTs. There was no difference between the early and late groups regarding the ATRS (mean difference [MD], -0.220; 95% CI, -4.489 to 4.049; P = .920). Likewise, we found no difference between the 2 groups in terms of the rerupture rate (odds ratio [OR], 1.107; 95% CI, 0.552 to 2.219; P = .775), the number of patients who returned to sports (OR, 0.766; 95% CI, 0.438 to 1.341; P = .351) and returned to work (OR, 0.706; 95% CI, 0.397 to 1.253; P = .234), the time to return to work (MD, -2.802 days; 95% CI, -6.525 to 0.921 days; P = .140), or the heel-rise work LSI (MD, -0.135; 95% CI, -6.243 to 5.973; P = .965). CONCLUSION: No significant differences were found between early controlled motion and weightbearing compared with immobilization and late weightbearing regarding the ATRS, the rerupture rate, return to sports activity and work, and the heel-rise work in nonoperatively treated patients with acute ATR.

Cardioprotective effect of saffron total glycoside tablets in patients with breast cancer receiving anthracycline-based chemotherapy: study protocol for a multicentre, randomised, parallel, double-blind, placebo-controlled clinical trial.

BACKGROUND: Breast cancer is the most common cancer worldwide. Anthracyclines, alone or in combination with other chemotherapeutic agents, are the most effective chemotherapy agents against breast cancer. However, the dose-dependent cardiotoxicity of anthracyclines is a serious drawback in clinical treatment. Considerable efforts have been made to establish suggestions to avoid anthracycline-induced cardiotoxicity. Crocin extracted from saffron has potential cardioprotective effects against anthracycline-induced cardiotoxicity. The aim of this study was to estimate the cardioprotective effects and safety of saffron total glycoside tablets relative to placebo in patients with breast cancer undergoing anthracycline-based chemotherapy. METHODS: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A sample of 200 participants (100 per group) with breast cancer will be randomly assigned to receive either saffron total glycoside tablet or placebo (four tablets each time, three times each day) for 6 months. Each participant will be interviewed three times: baseline (visit 1), after 3 months (visit 2), and after 6 months (visit 3). The primary outcome is to confirm if administration of saffron total glycoside tablets reduces the rate of cardiotoxicity relative to that with placebo. Secondary outcomes include new arrhythmic events, and cardiac troponin I and N-terminal pro-B-type natriuretic peptide levels. The quantity, quality, and severity of the adverse events will be carefully documented. DISCUSSION: We look forward to obtaining high-quality evidence that can be used to formulate clinical practice guidelines. Thus, the findings of this study are expected to help fill the current gap in cardiotoxicity prevention drugs. TRIAL REGISTRATION: This trial was published in the Chinese Clinical Trial Registry (No. ChiCTR2000041134, registered on 19th December 2020).

Effect of soft inflatable orthosis on the medial longitudinal arch in patients with flexible flatfoot deformity.

BACKGROUND: Orthoses can stabilize the foot and restore the medial longitudinal arch for symptomatic flexible flatfoot. However, the effectiveness of orthoses remains controversial. The purpose of this study was to evaluate effectiveness of a customized soft inflatable orthosis on the medial longitudinal arch of flexible flatfoot patients under load. METHODS: We obtained CT scans of the feet of 14 healthy volunteers and 14 patients with flexible flatfoot under non- and simulated weight-bearing conditions. Then CT scans under the same conditions were taken for patients with flexible flatfoot equipped with soft inflatable orthosis. Three-dimensional models of the medial longitudinal arch and hindfoot were constructed from CT images. The three-dimensional mobility of the medial longitudinal arch joints under load was compared between patients with flexible flatfoot equipped with soft inflatable orthosis or not. FINDINGS: From non- to simulated weight-bearing condition, the eversion and dorsiflexion of the talocalcaneal joint, the eversion of the talonavicular joint, the abduction and dorsiflexion of the cuneonavicular joint, and the dorsiflexion of the first tarsometatarsal joint were significantly larger in patients with flexible flatfoot than healthy volunteers. The customized soft inflatable orthosis could reduce the eversion of the talonavicular joint and the eversion and dorsiflexion of the talocalcaneal joint. INTERPRETATION: The soft inflatable orthosis is effective to improve medial longitudinal arch height and reduce excessive mobility of joints for flexible flatfoot deformity. The results of this study could provide evidence for the optimal orthosis design to treat flexible flatfoot in the future.

Analysis of the main soft tissue stress associated with flexible flatfoot deformity: a finite element study.

A better understanding of soft tissue stress and its role in supporting the medial longitudinal arch in flexible flatfoot could help to guide the clinical treatment. In this study, a 3-Dimensional finite element (FE) foot model was reconstructed to measure the stress of the soft tissue, and its variation in different scenarios related to flexible flatfoot. All bones, cartilages, ligaments and related tendons around the ankle, and fat pad were included in the finite element model. The equivalent stress on the articular surface of the joints in the medial longitudinal arch and the maximum principal stress of the ligaments around the ankle were obtained. The results show that the plantar fascia (PF) is the main tissue in maintaining the medial longitudinal arch. The equivalent stress of all the joints in the medial longitudinal arch increases when the PF attenuation and the talonavicular joint increases, while other joints decreases when all the three tissue attenuation. Moreover, the maximum principal stress variation of calcaneofibular ligament is largest when the PF attenuation and the tibionavicular ligament and posterior tibiotalar ligament are largest when the posterior tibial tendon (PTT) attenuation. The maximum principal stress variation of tibionavicular ligament and posterior tibiotalar ligament are even larger when all the three tissue attenuation. These findings support that the PF is the main factor in maintaining the medial longitudinal arch. The medial longitudinal arch collapse mainly affects the talonavicular joint and the calcaneofibular ligament, the tibionavicular ligament and the posterior tibiotalar ligament. This approach could help to improve the understanding of adult-acquired flatfoot deformity (AAFD).

The characteristics and prognostic significance of esophageal squamous cell carcinoma with synchronous multiple lesions: over 10-year experience.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is occasionally observed with synchronous multiple tumor lesions. Our study is aiming to define the clinical and prognostic features of this pathological subtype. METHODS: This study included a large cohort of 1126 ESCC patients received esophagectomy with systemic lymph-node dissection between 2003 and 2013 in Sun Yat-sen University Cancer Center. The characteristics and prognostic significance of ESCC with multiple lesions were analyzed. The propensity score matching was performed to balance the baseline clinical characteristics. RESULTS: A total of 103 patients (9.1%) with 216 synchronous multiple lesions were identified from postoperative gross samples. Among them, 94 patients had two lesions, and 8 patients had three lesions, while only one patient had four lesions. The consistency of pT stages and histological grade among tumor lesions from the same gross sample were 19.4% (20/103) and 37.9% (39/103), respectively. Additionally, the tumor sites, sizes, and even the pathological subtypes can be variant in one patient. The preoperative upper gastrointestinal endoscopy could only identified 80.1% of the multiple tumor lesions. The male gender (P = 0.012), positive personal cancer history (P < 0.001), and higher pN stages (P < 0.001) were independent risk factors for synchronous multiple lesions. Patients with multiple lesions showed significantly lower survival rate (P = 0.002), and the multiple-lesion was an independently adverse prognostic factor in operable ESCC (P = 0.002). CONCLUSION: ESCC with multiple lesions had unique clinical features and should not be simply treated as the one-lesion ESCC. Due to its worse prognostic impact, advanced multidisciplinary therapies should be considered for patients with multiple esophageal tumor lesions.

ATAD2 interacts with C/EBPß to promote esophageal squamous cell carcinoma metastasis via TGF-ß1/Smad3 signaling.

BACKGROUND: Distant metastasis is the leading cause of death for esophageal squamous cell carcinoma (ESCC) with limited treatment options and unsatisfactory effectiveness. Bromodomain (BRD) containing proteins are emerging targets for cancer therapy with promising effects. As a unique member of BRD family, the function and molecular mechanism of ATAD2 in cancer development is seldomly investigated. METHODS: The clinical impact of ATAD2 was assessed both at RNA and protein level in 75 and 112 ESCC patients separately. The biological function of ATAD2 was investigated in vitro and in vivo. Signaling pathway and downstream effectors of ATAD2 were identified by RNA sequencing, luciferase reporter, co-immunoprecipitation, chromatin immunoprecipitation, immunofluorescence and western blot assay. RESULTS: We found that elevated ATAD2 expression was significantly associated with lymph node metastasis, advanced clinical stage as well as poor survival of ESCC patients. Silencing ATAD2 significantly suppressed ESCC cell migration and invasion in vitro, and inhibited tumor growth and lung metastasis in vivo. Mechanically, we identified a new cofactor, C/EBPß. ATAD2 directly interacted with C/EBPß and promoted its nuclear translocation, which directly bound to the promoter region of TGF-ß1 and activated its expression. Further, we demonstrated that TGF-ß1 activated its downstream effectors in a Smad3 dependent manner. In addition, we further found that ATAD2 promoted ESCC metastasis through TGF-ß signaling induced Snail expression and the subsequent epithelial-mesenchymal transition. CONCLUSION: Our findings demonstrated the pro-metastatic function of ATAD2 and uncovered the new molecular mechanism by regulating C/EBPß/TGF-ß1/Smad3/Snail signaling pathway, thus providing a potential target for the treatment of ESCC metastasis.

Detection and structural characterization of the metabolites of dihydroresveratrol in rats by liquid chromatography coupled to high-resolution tandem mass spectrometry.

RATIONALE: Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti-oxidant and anti-inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats. METHODS: The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high-resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions. RESULTS: A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3'-hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites. CONCLUSIONS: The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats.

Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3 for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data.

BACKGROUND: Colorectal cancer (CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC (ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic. AIM: To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS. METHODS: ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005, to October 1, 2015, were studied. Expression of autophagy-related proteins [Beclin1, microtubule-associated protein 1A/B-light chain 3 (LC3), and 4E-binding protein 1 (4E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed. RESULTS: In CACO-2 cells exposed to cetuximab, LC3 and 4E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients, immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3 (0.657, P < 0.001) and 4E-BP1 (0.211, P = 0.042) in ACRC tissues. LC3 was significantly overexpressed in tumor tissues compared to normal tissues (P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1 (P = 0.010) and 4E-BP1 (P = 0.005), pathological grade (P = 0.002), and T stage (P = 0.004) were independent prognostic factors for overall survival (OS). CONCLUSION: The effect of cetuximab on colon cancer cells might be improved by autophagy. LC3 is overexpressed in tumor tissues, and Beclin1 and 4E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.

Correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction.

BACKGROUND: The purpose of this study was to evaluate correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction flatfoot under loading. METHODS: CT scans of 15 healthy feet and 15 feet with stage II posterior tibial tendon dysfunction flatfoot were taken both in non- and simulated weight-bearing condition. The CT images of the hindfoot and medial longitudinal arch bones were reconstructed into three-dimensional models with Mimics and Geomagic reverse engineering software. The three-dimensional complex mobility of each joint in the medial longitudinal arch and their correlation with the medial arch angle change were calculated. RESULTS: From non- to simulated weight-bearing condition, the medial arch angle change and the medial longitudinal arch joints mobility were significant larger in stage II posterior tibial tendon dysfunction flatfoot (p<0.05). The eversion of the talocalcaneal joint, the proximal translation of the calcaneus relative to the talus, the dorsiflexion of the talonavicular joint, the dorsiflexion and abduction of the medial cuneonavicular joint, and the lateral translation of the medial cuneiform relative to the navicular, and the dorsiflexion of the first tarsometatarsal joint were all significantly correlated to the medial arch angle change in stage II posterior tibial tendon dysfunction flatfoot (all r>0.5, p<0.05). CONCLUSIONS: There is increased mobility in the medial longitudinal arch joints in stage II posterior tibial tendon dysfunction flatfoot and the medial arch angle change under loading causes displacement not only at hindfoot joints but also involve midfoot and forefoot joint.

Algorithms designed for compressed-gene-data transformation among gene banks with different references.

BACKGROUND: With the reduction of gene sequencing cost and demand for emerging technologies such as precision medical treatment and deep learning in genome, it is an era of gene data outbreaks today. How to store, transmit and analyze these data has become a hotspot in the current research. Now the compression algorithm based on reference is widely used due to its high compression ratio. There exists a big problem that the data from different gene banks can't merge directly and share information efficiently, because these data are usually compressed with different references. The traditional workflow is decompression-and-recompression, which is too simple and time-consuming. We should improve it and speed it up. RESULTS: In this paper, we focus on this problem and propose a set of transformation algorithms to cope with it. We will 1) analyze some different compression algorithms to find the similarities and the differences among all of them, 2) come up with a naïve method named TDM for data transformation between difference gene banks and finally 3) optimize former method TDM and propose the method named TPI and the method named TGI. A number of experiment result proved that the three algorithms we proposed are an order of magnitude faster than traditional decompression-and-recompression workflow. CONCLUSIONS: Firstly, the three algorithms we proposed all have good performance in terms of time. Secondly, they have their own different advantages faced with different dataset or situations. TDM and TPI are more suitable for small-scale gene data transformation, while TGI is more suitable for large-scale gene data transformation.

Achieving Higher Strength and Sensitivity toward UV Light in Multifunctional Composites by Controlling the Thickness of Nanolayer on the Surface of Glass Fiber.

The interphase between fiber and matrix plays an essential role in the performance of composites. Therefore, the ability to design or modify the interphase is a key technology needed to manufacture stronger and smarter composite. Recently, depositing nanomaterials onto the surface of the fiber has become a promising approach to optimize the interphase and composites. But, the modified composites have not reached the highest strength yet, because the determining parameters, such as thickness of the nanolayer, are hardly controlled by the mentioned methods in reported works. Here, we deposit conformal ZnO nanolayer with various thicknesses onto the surfaces of glass fibers via the atomic layer deposition (ALD) method and a tremendous enhancement of interfacial shear strength of composites is achieved. Importantly, a critical thickness of ZnO nanolayer is obtained for the first time, giving rise to a maximal relative enhancement in the interfacial strength, which is more than 200% of the control fiber. In addition, the single modified fiber exhibits a potential application as a flexible, transparent, in situ UV detector in composites. And, we find the UV-sensitivity also shows a strong correlation with the thickness of ZnO. To reveal the dependence of UV-sensitivity on thickness, a depletion thickness is estimated by a proposed model which is an essential guide to design the detectors with higher sensitivity. Consequently, such precise tailoring of the interphase offers an advanced way to improve and to flexibly control various macroscopic properties of multifunctional composites of the next generation.

The Effect of Cartilage Fragments on Femoral Tunnel Widening After Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Controlled Study.

PURPOSE: To analyze the effect of cartilage fragments on tunnel widening and tendon-bone integration at 2 years' follow-up after anterior cruciate ligament reconstruction (ACLR). METHODS: A prospective randomized controlled study was performed in 116 patients who underwent ACLR with autologous hamstring tendons augmented with cartilage fragments (study group, n = 56) or without any augmentation (control group, n = 60). All patients were followed up for 25.6 months (range, 24-28 months), and the International Knee Documentation Committee score, Lysholm score, and visual analog scale score were determined. Computed tomography scans of all patients were obtained 2 years after surgery to evaluate the diameter of the femoral tunnel and thereby assess the amount of tunnel widening. Magnetic resonance imaging evaluation was performed 2 years postoperatively to evaluate the status of the graft in the femoral tunnel. In addition, 5 patients underwent biopsy of the tendon-bone interface at 24 months postoperatively with histologic assessment and transmission electron microscopy. RESULTS: A total of 107 patients completed the follow-up. There were no significant differences between the 2 groups in terms of International Knee Documentation Committee score (P = .07), Lysholm score (P = .10), and visual analog scale score (P = .57) at 24 months' follow-up. The femoral tunnel diameter and the tunnel widening percentage in the study group were significantly smaller than those in the control group (P < .001). The signal-noise quotient value of the graft in the femoral tunnel was 10.4 ± 7.0 in the study group, which was significantly lower than that in the control group (19.5 ± 9.2, P < .001). Histologic studies of the tendon-bone interface showed that there were more bone formations containing chondroid cells with aligned connective tissue in the study group compared with the control group; in addition, the diameter of the collagen fibrils in the study group was considerably thicker than that in the control group (P < .05). CONCLUSIONS: The use of cartilage fragments was effective in preventing femoral tunnel widening and seemed to promote the tendon-bone integration process after ACLR. LEVEL OF EVIDENCE: Level II, prospective randomized controlled study.