A nomogram to predict intracranial hypertension in moderate traumatic brain injury patients.

OBJECTIVE: Patients with moderate traumatic brain injury (TBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which moderate TBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in moderate TBI patients. METHODS: Baseline data collected on admission of 296 moderate TBI patients with Glasgow Coma Scale (GCS) score of 9-11 was collected and analyzed. Multi-variable logistic regression modeling with backward stepwise elimination was used to develop a prediction model for IHT. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. Finally, the prediction model was validated in a separate cohort of 122 patients from 3 hospitals. RESULTS: Four independent prognostic factors for IHT were identified: GCS score, Marshall head computed tomography score, injury severity score and location of contusion. The C-statistic of the prediction model in internal validation was 84.30% (95% confidence interval [CI]: 0.794-0.892). The area under the curve for the prediction model in external validation was 82.80% (95% CI: 0.747∼0.909). CONCLUSIONS: A prediction model based on baseline parameters was found to be highly sensitive in distinguishing moderate TBI patients with GCS score of 9-11 who would suffer IHT. The high discriminative ability of the prediction model supports its use in identifying moderate TBI patients with GCS score of 9-11 who need ICP-lowering therapy or invasive ICP monitoring.

FNDC5 prevents oxidative stress and neuronal apoptosis after traumatic brain injury through SIRT3-dependent regulation of mitochondrial quality control.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

Multimodality Therapy, Followed by Laparoscopic Gastrectomy, for Unresectable Gastric Cancer With Outlet Obstruction and Bulky N2 Metastases.

BACKGROUND: Patients who have gastric cancer with outlet obstruction (GCOO) and bulky N2 metastases cannot undergo curative resection and tolerate chemotherapy poorly, which may be improved by multimodality therapy (MMT) combined with laparoscopic gastrectomy. PATIENTS AND METHODS: The records of patients with GCOO and bulky N2 metastases who received MMT including nasojejunal feeding combined with preoperative chemotherapy (PCT), followed by laparoscopic exploration [enteral nutritional (EN) group] in sequence or laparoscopic gastrojejunostomy (LGJ) before PCT plus laparoscopic gastrectomy (LGJ group) were retrospectively reviewed. Prognostic Nutritional Index, gastric outlet obstruction scoring system grade, quality of life, response to PCT, surgical outcomes, and long-term survival were analyzed. RESULTS: Fifty-four consecutive patients with GCOO and bulky N2 metastases were identified. The Prognostic Nutritional Index and Nutritional Risk Screening-2002 score of patients were significantly improved as a result of multimodal therapy, but no superiority was demonstrated between the EN group and the LGJ group. The quality of life (52.6 ± 11.4 vs 68.2 ± 13.5, P = 0.036) and gastric outlet obstruction scoring system (P < 0.05) of patients in the LGJ group were better compared with the EN group. The rate of laparoscopic D2 gastrectomy (94.3% vs 92.9%, P = 0.64) and R0 resection (91.4% vs 92.9%, P = 0.53) in the EN group was similar to the LGJ group. There were no significant differences for the 5-year overall survival rate (63.2% vs 57.1, P = 0.86) and the 5-year relapse-free survival rate (42.9% vs 53.8%, P = 0.54) of patients in the EN group compared with the LGJ group. CONCLUSIONS: MMT including EN support or laparoscopic gastrojejunostomy followed by laparoscopic D2 gastrectomy is a feasible and effective treatment for patients with GCOO and bulky N2 metastases.

Development and validation of a nomogram predictive model for colorectal adenoma with low-grade intraepithelial neoplasia using routine laboratory tests: A single-center case-control study in China.

Background: Colorectal cancer (CRC) is the third most common cancer in the world and has a high mortality rate. Colorectal adenoma (CRA) is precancerous lesions of CRC. The purpose of the present study was to construct a nomogram predictive model for CRA with low-grade intraepithelial neoplasia (LGIN) in order to identify high-risk individuals, facilitating early diagnosis and treatment, and ultimately reducing the incidence of CRC. Methods: We conducted a single-center case-control study. Based on the results of colonoscopy and pathology, 320 participants were divided into the CRA group and the control group, the demographic and laboratory test data were collected. A development cohort (n = 223) was used for identifying the risk factors for CRA with LGIN and to develop a predictive model, followed by an internal validation. An independent validation cohort (n = 97) was used for external validation. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate discrimination ability, accuracy and clinical practicability of the model. Results: Four predictors, namely sex, age, albumin and monocyte count, were included in the predictive model. In the development cohort, internal validation and external validation cohort, the area under the curve (AUC) of this risk predictive model were 0.946 (95%CI: 0.919-0.973), 0.909 (95 % CI: 0.869-0.940) and 0.928 (95%CI: 0.876-0.980), respectively, which demonstrated the model had a good discrimination ability. The calibration plots showed a good agreement and the decision curve analysis (DCA) suggested the predictive model had a high clinical net benefit. Conclusion: The nomogram model exhibited good performance in predicting CRA with LGIN, which can aid in the early detection of high-risk patients, improve early treatment, and ultimately reduce the incidence of CRC.

Correlation between IFNAR1 expression in peripheral blood T lymphocytes and inflammatory cytokines, tumor-infiltrating lymphocytes, and chemosensitivity in patients with colorectal cancer.

IFN-α receptor (IFNAR) is critical for maintaining the crosstalk between cancer cells and lymphocytes. We investigated IFNAR1 expression in peripheral blood CD4+ and CD8+ T cells and explored their relationships with plasma cytokines, chemosensitivity and infiltrated T cells in the tumor microenvironment (TME) of colorectal cancer (CRC). The levels of IFNAR1, IFN-γ, and PD1 in peripheral T cells were tested using flow cytometry. Immunohistochemical staining of IFNAR1 in CRC tissues was performed. A cytometric bead array was used to determine the plasma concentrations of cytokines. In CRC patients, IFNAR1 levels were significantly increased in peripheral blood T cells, and plasma IL-6 levels were also significantly increased. Pearson correlation analysis revealed that IFNAR1 expression in CD8+ T cells was negatively associated with plasma IL-2, IFN-γ, and TNFα. IFNAR1 expression in CD4+ T cells was positively associated with TME infiltrated levels of CD8+ T cells. The levels of CD8+ T cells with IFNAR1 and plasma IFN-γ were associated with chemosensitivity. Collectively, IFNAR1 levels in CD4+ and CD8+ T cells were significantly upregulated in CRC patients and positively associated with T-cell infiltration. IFNAR1 may be a chemotherapy biomarker for predicting response.

Long-Read Nanopore Sequencing Identifies Mismatch Repair-Deficient Related Genes with Alternative Splicing in Colorectal Cancer.

Background: Alternative splicing (AS) plays a crucial role in regulating the progression of colorectal cancer (CRC), but its distribution remains to be explored. Here, we aim to investigate the genes edited by AS which show differential expression in patients with mismatch repair deficiency (dMMR)/microsatellite instability (MSI). Materials and Methods: We applied long-read nanopore sequencing to determine the mRNA profiles and screen AS genes using Oxford Nanopore Technologies (ONT) method in ten paired CRC tissues. CRC tissue and plasma samples were used to validate the differential genes with AS using real-time fluorescent quantitative PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ONT sequencing identified 404 genes were downregulated, and 348 genes were upregulated in MSI cancer tissues compared with microsatellite stability (MSS) cancer tissues. In total, 6,200 AS events were identified in 2,728 mRNA transcripts. WGCNA revealed dMMR/MSI-correlated gene modules, including INHBA and RPL22L1, which were upregulated; conversely, HMGCS2 was downregulated in MSI cancer. Overexpression of RPL22L1, INHBA, and CAPZA1 was further confirmed in CRC tissues. INHBA was found to be associated with tumor lymphatic metastasis. Importantly, the levels of INHBA in CRC plasma were significantly increased compared with those in noncancer plasma. INHBA showed a higher level in dMMR/MSI CRC than in MSS CRC, indicating that INHBA is a useful biomarker. Conclusion: Our results showed that ONT-identified genes provide a pool to explore AS-associated markers for dMMR/MSI CRC. We demonstrated INHBA as a promising signature for clinical application in predicting tumor lymphatic metastasis and screening dMMR/MSI candidates.

The Efficacy of Combined Therapy of Regorafenib with Detoxicating and Stasis Softening Chinese Herbal Spleen Tonics in Mid-/Late-Stage Hepatocellular Carcinoma.

Objective: To explore the efficacy of combined therapy of Regorafenib with detoxicating and stasis softening Chinese herbal spleen tonics (DSS-splenic tonics) in mid-/late-stage hepatocellular carcinoma. Methods: Retrospective observational data of 120 patients were obtained, 60 of which received combined therapy of DSS-splenic tonics and regorafenib. Adverse event, overall survival (OS), and time-to-progress (TTP) were analyzed. Synergistic effect of DSS-spleen tonics was found and validated in human hepatocellular carcinoma HCCLM3 cell line and xenograft mouse models. Results: Combination of regorafenib and DSS-splenic tonics also slightly extended the TTP and OS compared with treatment of regorafenib alone, suggesting DSS-splenic tonics has synergistic effect with regorafenib. Both Regorafenib and DSS-spleen tonics exerted inhibitory effect on cell viability and invasion capability of HCCLM3 cells, and combining both could enhance the antitumor effect. At molecular level, we found that VEGF, HIF-1α, MVD, and VEGF2 were all suppressed by regorafenib and DSS-splenic tonics. These results suggest that DSS-spleen tonics function synergistically with regorafenib in HCC by enhancing the regulation of regorafenib on VEGF, MMP-2, HIF-1α, and MVD, and may diminish angiogenesis during HCC progression. Conclusion: DSS-spleen tonics could exert synergistic antitumor effect with regorafenib via targeting VEGF.

Comparison of three different treatment methods for traumatic and Iatrogenic peripheral artery pseudoaneurysms.

OBJECTIVE: To compare the efficacy of open surgery (OS), endovascular interventions (EIs), and ultrasound-guided thrombin injection (UGTI) for the treatment of peripheral arterial pseudoaneurysms (PAs). METHODS: From January 1, 2001, to February 10, 2021, 38 patients diagnosed with traumatic and iatrogenic PAs treated with OS, EI, and UGTI were retrospectively analyzed. There were 18 females and 20 males, with an age of 56.47 ± 14.08 years (range,17-87 years). Anesthesia modality, operation duration, blood transfusion, duration of hospital stay, primary and secondary success rates, and complication rate were used to evaluate the surgical outcomes. RESULTS: There were 11 cases under regional anesthesia and 4 under general anesthesia in OS group, 9 under regional anesthesia and 1 under general anesthesia in EI group, and no regional or general anesthesia was required in UGTI group. There was no significant differences between any two groups (χ2  = 39.80, p < 0.05). The blood tranfusion amount (units) were 3.6 ± 6.0, 0.8 ± 2.5, 0.0 ± 0.0 for OS, EI, and UGTI groups, respectively, with significant difference between OS and UGTI groups (F = 3.03, p < 0.05). The operation duration (minutes) of OS, EI, and UGTI groups were 80.0 ± 41.9, 56.0 ± 8.4, and 22.7 ± 5.3, respectively, with significant difference between any two groups (F = 15.69, p < 0.05). The duration of hospital stay (days) were 47.7 ± 39.0, 31.5 ± 17.6, and 16.3 ± 9.5, repectively, with significant difference between any two groups (F = 47.73, p < 0.05). The primary clinical success rates were 80% (12/15), 90% (9/10), and 92.3% (12/13) in OS,EI, and UGTI groups, respectively, with no significant difference between any two groups (χ2  = 0.34, p > 0.05). The secondary clinical success rates were 100% for all three groups. The overall complication rates of OS, EI, and UGTI groups were 20% (3/15), 10% (1/10), and 7.7% (1/13), respectively, with no significant difference between any two groups (χ2  = 1.00, p > 0.05). The infection rates were 13.3% (2/15), 10% (1/10), and 0% (0/13) in OS, EI, and UGTI groups respectively, with no significant difference between any two groups (χ2  = 1.80, p > 0.05). The reintervention rates were 6.7% (1/15), 0% (0/10), 7.7% (1/13) in OS, EI, and UGTI groups, respectively, with no significant difference between two groups (χ2  = 0.95, p > 0.05). Neuralgia was relieved in all patients. CONCLUSIONS: OS, EI, and UGTI are efficacious and safe options for the treatment of appropriate patients with traumatic and iatrogenic PAs. UGTI would be considered as a first-line therapy for this condotion.

Long-term outcomes after extra-levator versus conventional abdominoperineal excision for low rectal cancer.

PURPOSE: Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. METHODS: One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. RESULTS: Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). CONCLUSION:  Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

Computed tomographic parameters correlate with coagulation disorders in isolated traumatic brain injury.

BACKGROUND AND OBJECTIVE: The imbalanced hemostatic equilibrium caused by brain tissue or vessel damage underlies the pathophysiology of traumatic brain injury (TBI)-induced coagulopathy, and cranial computed tomography (CT) is the gold standard for evaluating brain injury. The present study aimed to explore the correlation between quantitative cranial CT parameters and coagulopathy after TBI. METHODS: We retrospectively collected the medical records of TBI patients with extracranial abbreviated injury scale (AIS) scores <3 who were admitted to our institution. The quantitative cranial CT parameters of patients with and without coagulopathy were compared, and univariate correlation analysis between CT parameters and coagulation subtest values and platelet counts was performed. The predictors for each subtest of coagulation function were probed by multivariate regression. RESULTS: TBI patients with coagulopathy had a larger intracerebral haematoma/contusion (ICH/C) volume (p < 0.001), a higher incidence of compressed basal cisterns (p = 0.015), a higher Graeb score (p < 0.001) and subarachnoid haematoma (Fisher's scaling score) (p = 0.019) than those without coagulopathy. IH/C volume was identified as an independent risk factor for predicting coagulopathy. ICH/C volume showed a significantly positive correlation with APTT (Pearson's correlation = 0.333, p < 0.001), while a significant negative correlation with PLT (Pearson's correlation = - 0.312, p < 0.001). CONCLUSION: ICH/C volume was a main quantitative cranial CT parameter for predicting coagulopathy, suggesting that parenchymal brain damage and vessel injury were closely associated with coagulopathy after TBI.

Horizontal Rafting Plate for Treatment of the Tibial Plateau Fracture.

OBJECTIVE: This study aimed to investigate the value of a horizontal rafting plate in treating tibial plateau fractures. METHODS: The data of 24 patients in whom a horizontal rafting plate was used to treat a tibial plateau fracture between October 2014 and January 2018 were retrospectively analyzed, including 16 males and 8 females, aged 21-63 years old, with an average of 40 ± 14.68 years. The fractures included 13 in the left knee and 11 in the right knee. The places where the horizontal rafting plate were used included the anterior margin of tibia, anterolateral tibia, and posterolateral tibia. All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last follow-up, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the Rasmussen functional score. Computed tomography (CT) scanning and three-dimensional reconstruction were performed preoperatively and postoperatively, with the quality of reduction of the fractured articular surface clarified by the final follow-up. The flexion and extension abilities of the knee joint were also measured in the postoperative follow-up. RESULTS: Preoperative CT scanning showed that the gap of the tibial plateau was 8.00 ± 1.40 (5-24) mm. The heights of the fracture of the articular surface at all three sites during the final follow-ups were significantly different from the height before the surgery (P < 0.05). The vertical distance between the articular line and the highest point of the articular surface after reduction was 0.17 ± 0.05 mm. Anatomic reductions were obtained in 24 patients. The Rasmussen functional score after surgeries was 27.25 ± 0.94 points. Bony union was achieved in all the patients. According to the Rasmussen radiological criteria, the scores during the last follow-up were as follows: the total score was 13-18 points, with an average of 16.00 ± 1.72 points; the scores were excellent in 17 cases and good in seven cases. Therefore, 100% of results were excellent or good. No infection or fracture nonunion was found. CONCLUSION: Using a horizontal plate can be an effective method for treating special types of fractures of the tibial plateau, including the anterior margin and anterolateral and posterolateral tibial plateau, with satisfactory treatment efficacy.

Polymorphism in GRHL2 gene may contribute to noise-induced hearing loss susceptibility: a meta-analysis / Polimorfismo no gene GRHL2 pode contribuir para a suscetibilidade à perda auditivainduzida por ruído: uma metanálise

Abstract Instruction: Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting. Objective: The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss. Methods: A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association. Results: Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594-0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062-1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514-0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054-1.379). Conclusion: Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

Resumo Introdução: Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes. Objetivo: Identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído. Método: Uma pesquisa abrangente foi feita para coletar dados até 8 de julho de 2018. No fim, quatro artigos elegíveis foram incluídos nesta metanálise, abrangeram 2.410 indivíduos. As odds ratios agrupadas com intervalos de confiança de 95% foram usadas para avaliar a força da associação. Resultados: Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379). Conclusão: O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

Polymorphism in GRHL2 gene may contribute to noise-induced hearing loss susceptibility: a meta-analysis.

INSTRUCTION: Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting. OBJECTIVE: The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss. METHODS: A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association. RESULTS: Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio=0.707, 95% confidence interval=0.594-0.841) and allele model (G allele vs. A allele, odds ratio=1.189, 95% confidence interval=1.062-1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio=0.634, 95% confidence interval=0.514-0.783) and allele model (G allele vs. A allele, odds ratio=1.206, 95% confidence interval=1.054-1.379). CONCLUSION: Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

Rhizoma Paridis total saponins alleviate H2O2­induced oxidative stress injury by upregulating the Nrf2 pathway.

Rhizoma Paridis total saponins (RPTS) is an active substance isolated from the traditional Chinese medicine Rhizoma Paridis, which possesses multiple biological activities. The aim of the present study was to explore the roles and mechanisms of RPTS in oxidative stress injury of ARPE­19 human retinal pigment epithelial cells. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) and apoptosis were determined by Cell Counting kit­8 assay and flow cytometry, respectively. Enzyme­linked immunosorbent assay was performed to detect the expression of oxidative stress markers. Western blotting and reverse transcription­quantitative polymerase chain reaction were used to determine the expression levels of related genes and proteins. The results revealed that RPTS enhanced cell viability and reduced H2O2­induced oxidative stress of ARPE­19 human retinal pigment epithelial cells. RPTS increased the MMP of ARPE­19 cells compared with in H2O2­treated ARPE­19 cells. In addition, RPTS suppressed ROS production and apoptosis of H2O2­treated ARPE­19 cells. Additionally, RPTS modulated the expression levels of apoptosis­associated proteins and the nuclear factor 2­related factor 2 (Nrf2) pathway. In conclusion, RPTS alleviated H2O2­induced oxidative stress injury by upregulating the Nrf2 pathway. The potential effects of RPTS on protection against H2O2­induced apoptosis of ARPE­19 cells suggested that RPTS may be a potential therapeutic target for preventing age­related macular degeneration.

Surgical Treatment of Lateral Tibial Plateau Fractures Involving the Posterolateral Column.

OBJECTIVE: To summarize the indications and the clinical effects of a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach in the treatment of fractures of the lateral tibial plateau involving the posterolateral column. METHODS: Eleven patients with lateral tibial plateau fractures were included in the present study. The fractures were Schatzker type II or lateral platform fractures involving posterolateral column. The anterolateral combined posterolateral approach (lateral + posterolateral locking plate fixation) was applied in 7 patients and 4 patients underwent transfibular neck osteotomy (lateral + posterolateral locking plate fixation + 1/4 tubular plate edge fixation, fibular osteotomy with Kirschner wire tension band fixation, and hollow nail fixation for upper tibiofibular joint). All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last followup, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the knee function evaluation criteria of the Hospital for Special Surgery (HSS). The Lachman test and the pivot-shift test were used to evaluate the anterior and posterior and rotational stability of the knee joint. The range of knee motion was recorded. RESULTS: Bone healing was achieved in all patients with fractures treated with a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach. At the last follow-up, both the Lachman test and the pivot-shift test results were negative. All patients had complete knee extension. For the combined anterolateral and posterolateral approach, the knee flexion angle was 110°-130°, with an average of 122.86° ± 7.56°. For the transfibular neck osteotomy approach, the knee flexion angle was 115°-130°, with an average of 120.00° ± 7.07°. For the patients in which the combined anterolateral and posterolateral approach was used, the Rasmussen score was 12-18 points, with an average of 16.00 ± 2.56 points. The results were excellent in 4 cases and good in 3 cases; therefore, 100% of results were excellent or good. For patients in which the transfibular neck osteotomy approach was used, the Rasmussen score was 10-18 points, with an average of 15.25 ± 3.77 points. The results were excellent in 2 cases, good in 1 case, and acceptable in 1 case; therefore, 75% of results were excellent or good. The HSS score for the combined anterolateral and posterolateral approach was 76-98 points, with an average of 88.43 ± 7.55 points. The results were excellent in 5 cases and good in 2 cases; therefore, 100% of results were excellent or good. The HSS score for the transfibular neck osteotomy approach was 74-96 points, with an average of 87.25 ± 9.43 points. The results were excellent in 3 cases and good in 1 case; therefore, 100% of results were excellent or good. There were no significant differences in operation time, surgical blood loss, fracture healing time, postoperative imaging score, and knee function evaluation between the two approaches. One patient who underwent transfibular neck osteotomy had a 3-mm step that gradually appeared, but no significant abnormalities were found in the width of the platform and the lower limb force line. One patient in whom the combined anterolateral and posterolateral approach was used showed numbness in the common peroneal nerve. No common peroneal nerve injury occurred through the transfibular neck osteotomy approach. CONCLUSIONS: The anterolateral combined posterolateral approach and the transfibular neck osteotomy approach are effective in the surgical treatment of lateral tibial plateau fractures involving the posterolateral column. However, the transfibular neck osteotomy approach is more suitable for the posterolateral plateau articular surface damaged with bone separation and displacement, deep collapse, cases involving a large range of the posterolateral column, especially fractures of the lateral tibial plateau in the upper tibiofibular syndesmosis area of the line connecting the anterior and posterior margin of the fibular head to the midpoint of the plateau.

Long-Term Outcomes of Ligation of the Inter-Sphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-Plug) in the Treatment of Trans-Sphincteric Perianal Fistula.

BACKGROUND The ligation of the inter-sphincteric fistula tract plus bioprosthetic anal fistula plug (LIFT-plug) is a new procedure in the treatment of trans-sphincteric perianal fistulas. The aim of this study was to evaluate its long-term outcomes. MATERIAL AND METHODS Clinical data of 78 patients with trans-sphincteric perianal fistula who were managed by the LIFT-plug technique between March 2014 to October 2016 were analyzed retrospectively. The operation time, healing rate, postoperative complications, recurrences, and length of stay were reviewed. RESULTS No serious complications occurred during the operation in all patients. The median follow-up was 30 months (16 to 47 months), clinical healing of the anal fistula occurred in 75 patients (96.2%). The median operative time was 25 minutes (18 to 45 minutes). The mean complete healing time was 16 days (9 to 46 days). The median healing time for the external anal fistula opening was 2 weeks (range, 2 to 3 weeks), and the inter-sphincteric groove incision healing time was 4 weeks (range, 3 to 7 weeks). The median hospital stay after operation was 5 days. Fistula recurred in 2 patients because of spontaneous expulsion of the plug at 7 days post-surgery; perianal abscess occurred in 1 patient. The anal function was evaluated in 70 patients of the 78 patients. Perfect control of continence was recorded for 97.1% of the patients (68 out of 70 patients). Two patients were identified to a rare complication of gas incontinence (Wexner score 1). CONCLUSIONS LIFT-plug procedure for the treatment of trans-sphincteric fistulas is a simple procedure with a high healing rate, minimal invasiveness, quick healing, and without disturbance to anal function. LIFT-plug is an ideal procedure for trans-sphincteric fistula.

Circular RNA circVAPA is up-regulated and exerts oncogenic properties by sponging miR-101 in colorectal cancer.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs with distinct properties and diverse physiological and pathological functions. However, the functions of circRNAs in colorectal cancer (CRC) remain elusive. This study aimed to investigate the functional roles of circVAPA in CRC. High-throughput RNA sequencing was performed in 4 paired CRC tissues, and circVAPA (hsa_circ_0006990), was identified as a potential functional circRNA. Using quantitative real-time polymerase chain reaction (qRT-PCR), circVAPA was found to be up-regulated in CRC patients' tissues and plasma. Furthermore, circVAPA level was associated with unfavorable clinicopathologic features in CRC. The area under curve (AUC) of ROC was 0.724, suggesting that plasma level of circVAPA could serve as a promising biomarker for CRC detection. Sanger sequencing confirmed the back-splice junction sequences of circVAPA. Actinomycin D and RNase R treatments suggested that circVAPA was highly stable compared with its linear counterpart, and qRT-PCR for the circVAPA level in nuclear and cytoplasmic fractions indicated that circVAPA was predominantly localized in the cytoplasm. Gain-of-function and loss-of-function studies in CRC cell lines indicated that circVAPA could promote CRC cell proliferation, migration, invasion, and inhibit apoptosis. miRanda software (v3.3a) was used to predict target miRNAs of circVAPA. Moreover, target miRNAs associated with the KEGG pathway of COLORECTAL CANCER (Entry: map05210; https://www.kegg.jp/) were screened using DIANA-miRPath v.3 platform (Reverse Search module; TarBase v7.0 method). The analyses by miRanda and miRPath suggested that circVAPA could potentially bind to hsa-miR-101-3p (miR-101) associated with the COLORECTAL CANCER pathway. Luciferase reporter assay confirmed a direct interaction between circVAPA and miR-101. Furthermore, circVAPA had no effect on the expression level of miR-101, and miR-101 over-expression had the similar tumor-suppressing effects as circVAPA silencing. The tumor-promoting effect of circVAPA over-expression could be reversed by the up-regulation of miR-101. These data demonstrated that circVAPA promoted CRC progression by sponging miR-101. In conclusion, we have verified that circVAPA is up-regulated in CRC patients' tissues and plasma, and exerts oncogenic properties by sponging miR-101 in CRC. CircVAPA could serve as a promising biomarker and a therapeutic target for CRC.

The efficacy of local liposomal bupivacaine infiltration on pain and recovery after Total Joint Arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Total Joint Arthroplasty (TJA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, Perioperative liposomal bupivacaine treatment is still a controversial subject in TJA. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of liposomal bupivacaine on pain and recovery after TJA. MATERIALS AND METHODS: Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials (RCTs), cohort studies were included in our meta-analysis. Twelve studies that compared liposomal bupivacaine groups with placebo groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. RCTs were included in our meta-analysis. RESULTS: Our study demonstrated that liposomal bupivacaine group was as effective as the placebo group in term of VAS score at 24 h (P = .09), 48 h (P = .97); Postoperative nausea (P = .72); and LOS (0.27). There was significant difference in terms of total morphine consumption at 24 h (P < .0001), 48 h (P = .0008). CONCLUSION: Our meta-analysis demonstrated that liposomal bupivacaine has similar pain control and functional recovery after TJA which compared with the control group. However, we still need large sample size, high-quality studies to explore the relationship between complications and dose response to give the final conclusion.

Structural Features of Alkaline Dioxane Lignin and Residual Lignin from Eucalyptus grandis × E. urophylla.

In the present study, lignin from eucalyptus was extracted with 80% alkaline dioxane (0.05 M NaOH) from ball-milled wood and subsequently fractionated by gradient acid precipitation from the filtrate. Meanwhile, the residual lignin was prepared by a double enzymatic hydrolysis process. The yield of the lignin extracted by alkaline dioxane (LA-2) was 29.5%. The carbohydrate contents and molecular weights of the gradient acid precipitated lignin fractions gradually decreased from 4.90 to 1.36% and from 7770 to 5510 g/mol, respectively, with the decline of the pH value from 6 to 2. Results from two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and 31P NMR spectroscopy showed an evident reduction of ß- O-4 ' linkages with the pH value decrease, while the contents of aliphatic -OH, phenolic -OH, and carboxylic groups displayed an increasing trend. Moreover, the residual lignin exhibited the highest molecular weight (11690 g/mol), the most abundant ß- O-4 ' linkages (71.1%), and the highest S/G ratio (4.68).