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Artemisinin and its derivatives, commonly known as antimalarial drugs, have gradually come to be regarded as potential antitumor agents, although their cytotoxic efficacy and mechanisms of action r...

An amino-modified multiwalled carbon nanotube (MWCNT) solid-phase extraction-based hydrophilic interaction liquid chromatography���tandem mass spectrometry (HILIC���MS/MS) method was developed for simultaneous determination of 13 paralytic shellfish toxins (PSTs) in bivalve mollusks. Shellfish samples were extracted with 1% acetic acid followed by cleanup using optimized MWCNT-NH2 based solid-phase extraction. Absorbed PSTs were eluted with 2 mL 1% acetic acid���acetonitrile (70/30, v/v). The separation was performed on a Waters BEH Amide column within 7.5 min utilizing 0.1% formic acid���acetonitrile and 2 mM ammonium acetate containing 0.1% formic acid as the mobile phase. The analytes were quantified by matrix-matched external standard curves with correlation coefficients�� exceeding 0.997 acquired in multiple reaction-monitoring mode. The limits of detection and quantitation in shellfish samples were from 2.76 to 9.8 ��g/kg and 9.11 to 39.3 ��g/kg, respectively. Recoveries at three spiked levels ranged from 71.4% to 97.8% with relative standard deviations less than 12.6%. The developed method was satisfactorily applied to the analysis of shellfish.

Objective To explore the safety and efficacy of percutaneous pedicle screw fixation combined with vertebroplasty for the treatment of stage III Kümmell disease. Methods The clinical data and follow‐up results of 22 patients with Kümmell disease who were admitted to our department from 2014 to 2018 were analyzed. There were 14 females and eight males, and the Age range was 58–81 years. All patients were followed up for 24 months. The treatment method was percutaneous pedicle screw fixation combined with vertebroplasty. The patient general information such as age, gender, bedrest time and location of fracture vertebrae were recorded. The clinical symptoms and imaging data of visual analogue scale (VAS), bone cement leakage, Oswestry Disability Index (ODI), Cobb angle, anterior, middle and posterior height of the diseased vertebral body, and complications were recorded before operation and during follow‐up. Results For patients enrolled, no bone cement leakage was observed during the operation; no patients developed infections after operation. The operation was safe and resulted in a short bedrest time. The VAS score and ODI index at 3 and 24 months postoperative (2.86 ± 0.83, 31.68% ± 6.21%; 3.0 ± 0.82, 32.78% ± 6.05%) were significantly lower than that recoded preoperatively (7.59 ± 0.59, 71.5% ± 8.84%) (P 0.05). Imaging data showed that the bone cement and screws were in good position and did not move during postoperative and follow‐up. The anterior, middle and posterior height of the diseased vertebral body measured 2 days after surgery (23.46 ± 4.72, 23.12 ± 3.05, 25.81 ± 2.22) and at last follow‐up (20.83 ± 4.48, 21.78 ± 2.74, 24.74 ± 1.93) were higher than that recorded preoperatively (13.08 ± 4.49, 12.93 ± 3.53, 19.32 ± 2.73) (P 0.05). Follow‐up for 24 months, there was no re‐fracture of the diseased vertebrae and internal fixation loosening, but two cases of adjacent vertebral refracture complications occurred, and the effect was good after PVP treatment. Conclusion Short‐segment percutaneous pedicle screw fixation combined with vertebroplasty in the treatment of stage III Kümmel disease can effectively restore the height of the diseased vertebrae, kyphosis correction, reduce trauma, prevent the diseased vertebral body from collapsing again, and effectively improves clinical symptoms., Schematic diagram of percutaneous pedicle screw fixation combined with vertebroplasty for the treatment of stage III Kümmell disease. (A, D) Stage III Kümmell disease: vertebral compression, Cobb angle enlargement, posterior vertebral cortical rupture with spinal cord compression. (B, E) Percutaneous pedicle screw fixation: decrease the Cobb angle, enlarge the upper and lower gap of the diseased vertebrae and restore the height of the diseased vertebrae. (C, F) Percutaneous vertebroplasty: injection of bone cement to fill the enlarged diseased vertebral cavity to restore the height and stability of the vertebral body.

Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib. α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergistically toxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy.

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

The ethanol and water extracts of 20 kinds of mushrooms from Sichuan Province, Southwest of China, were investigated for their antioxidant activity using DPPH assay. The results showed the ethanol extract of Serpula lacrymans, Daldinia concentrica, and Scleroderma verrucosum had well DPPH free radical scavenging activities 91.33%, 79.76% and 62.82%, respectively. Besides, the water extracts of Serpula lacrymans, Armillaria luteo-virens, and Lentinus edodes also possessed pretty high DPPH free radical scavenging activity were 95.59%, 88.76% and 86.93%, respectively. Based on the above comparison, the EC50 and total phenolic content of the ethanol extracts of Serpula lacrymans, Daldinia concentrica, and Scleroderma verrucosum were also measured. Their EC50 and total phenolic content valued of 17.87mg·mL-1, 11.19mg·mL-1 and 35.01mg·mL-1, as well as 0.0769μg·L-1, 0.0673μg·L-1 and 0.0545μg·L-1, respectively. The results showed there was a correlation between antioxidant activity and total phenolic content. Besides, the reaction time of the DPPH test affected the free radical scavenging, which reflected the difference of the extract component would impact the test method.

Background A skin flap is one of the most critical surgical techniques for the restoration of cutaneous defects. However, the distal necrosis of the skin flap severely restricts the clinical application of flap surgery. As there is no consensus on the treatment methods to prevent distal necrosis of skin flaps, more effective and feasible interventions to prevent skin flaps from necrosis are urgently needed. Stem therapy as a potential method to improve the survival rate of skin flaps is receiving increasing attention. Methods This review followed the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. Twenty studies with 500 animals were included by searching Web of Science, EMBASE, PubMed, and Cochrane Library databases, up until October 8, 2020. Moreover, the references of the included articles were searched manually to obtain other studies. All analyses were conducted using Review Manager V.5.3 software. Results Meta-analysis of all 20 studies demonstrated stem cell treatment has significant effects on reducing necrosis of skin flap compared with the control group (SMD: 3.20, 95% CI 2.47 to 3.93). Besides, subgroup analysis showed differences in the efficacy of stem cells in improving the survival rate of skin flaps in areas of skin flap, cell type, transplant types, and method of administration of stem cells. The meta-analysis also showed that stem cell treatment had a significant effect on increasing blood vessel density (SMD: 2.96, 95% CI 2.21 to 3.72) and increasing the expression of vascular endothelial growth factor (VEGF, SMD: 4.34, 95% CI 2.48 to 6.1). Conclusions The preclinical evidence of our systematic review indicate that stem cell-based therapy is effective for promoting early angiogenesis by up regulating VEGF and ultimately improving the survival rate of skin flap. In summary, small area skin flap, the administration method of intra-arterial injection, ASCs and MSCs, and xenogenic stem cells from humans showed more effective for the survival of animal skin flaps. In general, stem cell-based therapy may be a promising method to prevent skin flap necrosis.

To assess the effect of the mass-stiffness distribution of the cab and vibratory roller on the ride quality, the acceleration-frequency characteristics of the isolation systems are researched based on the nonlinear dynamic model of the vehicle. The complex domain is used to solve the vibration equations in the frequency region. The effect of the mass and stiffness parameters of the cab and vehicle is then analyzed via MATLAB software. The research results show that the resonant frequency of the cab's isolations and their acceleration-frequency is insignificantly affected by the mass-stiffness distributions in the case of without the excitation of the vibrator drum. Conversely, under an excitation 28 Hz of the vibrator drum, the mass-stiffness distributions strongly affect on the acceleration-frequency of the cab isolations, especially, when increasing the stiffness coefficient and reducing the cab mass with α= 1.5, the vehicle’s ride quality and structural durability of the vibratory rollers are greatly improved.

Dairy and fermented foods are common sources of dietary branched-chain fatty acids (BCFA) of chain lengths C13-C18 serving a putative prebiotic role and a component of human integument. Few studies have reported on nonfermented plant-derived BCFA in human diets or cosmetics. A three-ion monitoring method was adapted to confirm branch position of ultratrace (

Aims: To promote the rational exploration of the mushroom resources, this study evaluated the in vitro antioxidant activity of 16 kinds of mushrooms collected from the Sichuan province in China and completed the identification of the optimal active strains. Place and Duration of Study: School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan province, China. April 2019 to May 2020 (13 Months). Methodology: 16 kinds of mushrooms were collected in the wild. These strains were isolated and cultivated. The extract’s antioxidant activities of fermentation broth and mycelium were assessed using the DPPH radical-scavenging method. The higher activity strains were also evaluated by Trolox equivalent antioxidant capacity (TEAC) and the Ferric reducing antioxidant power (FRAP) assay. Meanwhile, the contents of total flavonoids and total phenols were determined. Finally, The highly active strains were identified by internal transcribed spacer (ITS) Identification. Results: All extract of fermentation broth and mycelium from 16 kinds of mushrooms had scavenging effects on DPPH. Among them, strain No. 6 and No. 7 exhibited obvious antioxidant capacity, and the scavenging rates of their fermentation broths on DPPH were 89.47% and 84.27%, respectively. And the results of TEAC and FRAP were consistent with those of DPPH. Besides, these two kinds of mushrooms were all rich in phenolic and flavonoid compounds, and the content in the fermentation broth was significantly higher than that in the mycelium, indicating that phenolic and flavonoid substances may be the material basis of their antioxidant effect. The strain No. 6 and No. 7 were confirmed to be Bjerkandera and Nigrospora sp, respectively by 16S nrDNA sequence identification. Conclusion: The results showed that Bjerkandera and Nigrospora sp. possessed the highest antioxidant capacities with rich total phenolic and total flavonoids. They could be potential sources of natural antioxidants for further exploration and application.

Objective Colorectal cancer (CRC) is a fatal disease, and tumor development is a complex cellular event involving a multistep cascade process involving proliferation, invasion, and migration. In recent years, it has been shown that microRNA-126 (miR-126) plays a key role in the tumorigenesis of CRC, but further studies are required to investigate the regulatory mechanisms through which this miRNA affects cell viability, autophagy, and apoptosis in CRC. We aimed to study the effect of miR-126 in gene regulation in CRC HCT116 cells. Methods CRC biopsy samples and normal colorectal tissue samples were used for miRNA profiling. Real-time quantitative PCR and WB were utilized to detect RNA and protein levels. MTT and colony formation assays were performed to examine cell viability. Furthermore, an immunofluorescence assay and Annexin V/PI flow cytometry were performed to detect autophagy and apoptosis, respectively. Results The expression of miR-126 was downregulated in CRC biopsies and cell lines compared with that in normal cells and tissues. The upregulation of miR-126 resulted in impaired viability and growth of CRC cells. Furthermore, with the overexpression of miR-126, cell autophagy was increased, as evidenced by LC3-I/II transformation and p62 degradation. Meanwhile, apoptosis induction was also observed because of the increased miR-126 levels. The autophagy inhibitor Bafilomycin A1 (BafA1) repressed both autophagy and apoptosis, indicating that miR-126 induced autophagy was responsible for the induction of apoptosis. A dual-luciferase reporter assay (DLRA) and bioinformatics prediction revealed that miR-126 silenced the mTOR gene by targeting the 3'-UTR. mTOR mRNA levels in CRC biopsy tissues and cell lines were upregulated to a greater extent than that in normal cells and tissues. Furthermore, HCT116 cells transfected with an miR-126 mimic showed a decreased expression of mTOR. In addition, the overexpression of mTOR counteracted miR-126 on autophagy and apoptosis. Conclusion Our study demonstrated that miR-126-induced can regulate the activity of CRC cells via autophagy and apoptosis and suggested a new mechanism of miR-126-mTOR interaction in CRC pathogenesis.

Background There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. Methods This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. Results A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2–19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2–3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353–0.599; p

Background and purpose: The use of hormone receptor agent drugs such as androgens (tamoxifen) for the treatment of moderate and severe breast pain has limitations such as cardiac, hepatic, and nephrotoxicity and gastrointestinal side effects. Therefore, there is a need to prescribe a new safe and effective topical treatment method to reduce the use of anti-inflammatory and hormonal agent drugs, the incidence of adverse effects and the financial burden on patients. This randomized controlled clinical trial investigates the clinical efficiency and safety of Skin‐patch of Ding Zi Gao (DZG) acupoint-application therapy for the treatment of moderate to severe Periodic mastalgia (MSPM), and provides a basis for the design of an optimized, safe and effective comprehensive treatment plan for MSPM.Methods: Sixty patients with moderate to severe Periodic mastalgia (MSPM) who met the inclusion criteria were selected from the breast clinic of Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University and randomly divided into 30 cases in the treatment group and 30 cases in the control group. The treatment group was treated by Skin‐patch of Ding Zi Gao (DZG) acupoint-application therapy, which was applied from the 3rd day after the end of menstruation, once a day, for 6-8 h each time, 14 times as a course of treatment, and the treatment was completed within 1 month, and the application was stopped during menstruation. The control group was treated with skin patches of placebo acupoint application, and the duration and course of treatment were the same as that of the treatment group. During the 14 day course of treatment and 2-month follow-up after the experiment, the main outcome indicators (including Breast pain improvement onset time, change in breast pain VAS score, change in patient's mood, sleep, Fullness in both flank, (McGill Pain Questionnaire) MPQ and secondary outcome indicators ( Including changes in breast nodule size and gland thickness guided by breast ultrasound, VAS pain score in the 2-month follow-up at the end of treatment, and adverse reactions), At the same time, the safety of the scheme was evaluated.RESULTS: There were no differences between the two groups in terms of age, body mass index, history of breastfeeding, family history of breast disease, history of allergies, history of breast surgery, or duration of breast pain (months) before recruitment. The comparison between pre-treatment and post-treatment showed that the time to onset of breast pain improvement, visual analogue score (VAS) of breast pain, improvement in mood, sleep, fullness in both flank and the MPQ were significantly lower in both groups after treatment, and the improvement was more significant in the treatment group than in the placebo control group (P < 0.05). Both groups showed significant reductions in improving patient mammography outcomes and VAS pain scores at two months of follow-up, but there were no significant differences between the groups. In terms of safety evaluation, no significant differences in the incidence of adverse events were found.CONCLUSION: point-application treatment with skin patches of Ding Zi Gao (DZG) therapy in patients with MSPM improved breast pain and swelling, reduced breast gland thickness, and decreased breast visual analogue pain score (VAS) and MPQ score. Its efficacy was significantly better than skin patches of placebo acupoint application therapy alone. This study provides a basis for the clinical application of DZG for MSPM.

Purpose: Iatrogenic coracoid and clavicle fracture is a known complication of drilling bone tunnels during anatomic coracoclavicular ligament reconstruction (ACCR). This study aims to measure the dimensions of coracoid process and clavicle in an Asian population to evaluate the suitability of drilling coracoid and clavicle tunnels for ACCR in Asians. Methods: Width measurements of 196 coracoids and 189 clavicles were obtained after reviewing all computed tomography (CT) scans of the shoulder performed over a 6 years period. Coracoid measurements were made on the CT slice which showed the maximum cross sectional width of the coracoid base. Medial to lateral measurements of the coracoid width were taken on an axial view, 4 mm above the identified junction of the coracoid base and glenoid base. Antero-posterior clavicle width was measured through a point directly above the midpoint of the coracoid and perpendicular to the long axis of the clavicle. Results: The overall mean coracoid width was 14.8 mm ± 2.54 mm (range 9.2-23.3 mm) and clavicle width was 17.1 mm ± 2.72 mm (range 11.1-25.3 mm). Conclusion: The Asian coracoid process is smaller than its Western equivalent. More research is required to validate this conclusion as no cadaveric studies with equivalent measurement techniques have been performed on Asians. Given the potentially narrower dimensions of the Asian coracoid process, extra precautions are required to minimize the risk of iatrogenic coracoid and clavicle fractures. Key words: Coracoclavicular ligament reconstruction; Coracoid process; Clavicle; Width

Sepsis commonly progresses to disseminated intravascular coagulation and induces the activation of heparanase (HPA) and the shedding of endothelial glycocalyx constituents, including syndecan-1 (SDC-1) and heparan sulphate (HS). However, the degradation of glycocalyx and its association with coagulation disorders remains undetermined. The present study aimed to evaluate the effect of unfractionated heparin (UFH) and N-acetylheparin (NAH), which is a non-anticoagulant heparin derivative, on endothelial glycocalyx and coagulation function in a lipopolysaccharide (LPS)-induced sepsis rat model, and to compare the differences observed in coagulation function between UFH and NAH. Experimental rats were randomly assigned to four groups: Control; LPS; UFH + LPS; and NAH + LPS. Rats were administered UFH or NAH and subsequently, ~1 min later, administered LPS (10 mg/kg; intravenous). The blood and lung tissues of rats were collected 0.5, 2 and 6 h after LPS injection, and were used for subsequent analysis. The results demonstrated that HPA activity and SDC-1 and HS levels increased, and this increase was associated with inflammatory cytokines and coagulation/fibrinolysis markers in the sepsis rat model. Histopathological examination was performed, and the lung injury score and lung wet/dry ratio indicated that UFH and NAH also significantly improved lung tissue injury. The results of the ELISA analysis demonstrated that UFH and NAH treatment: i) significantly decreased the levels of inflammatory cytokines including tumor necrosis factor-α and interleukin-6; ii) inhibited HPA activity and protected the integrity of the glycocalyx, which was identified by decreased HS and SDC-1 levels; and iii) decreased the levels of prothrombin fragment 1+2, thrombin-antithrombin complex, and plasminogen activator inhibitor-1 and increased the levels of fibrinogen and antithrombin-III. Preconditioning with UFH decreased the plasma activated partial thromboplastin time. These results indicated that UFH and NAH may alleviate sepsis-induced coagulopathy, and this effect may have been due to an inhibition of HPA activity and decrease in the shedding of the endothelial glycocalyx.

A below knee amputation (BKA) requires sufficient stump length for the fitting of a modern prosthesis. In cases of trauma where the levels of injury are unpredictable, achieving sufficient stump length can be a challenge. We described a case report of using the Ilizarov technique for bone lengthening at the residual BKA stump for a patient who sustained a mangled limb following a road traffic accident. Using this technique, we have successfully lengthened the tibial stump adequately for a functioning prosthesis. As shown in this case, we believe that this technique could attain an excellent outcome for a selected group of patients with short residual BKA stump. Key words: Below knee amputation; Stump lengthening; Ilizarov technique

BACKGROUND Pancreatic cancer is a major cause of cancer-related death, with a 5-year overall survival rate being below 5%. The main causes of poor prognosis in pancreatic cancer include easy metastasis, high recurrence rate, and robust drug resistance. Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer. However, due to drug resistance, the clinical effect is not satisfactory. ADAM28 is reported as a tumor promoter in some cancers, but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated. AIM To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer. METHODS RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer. SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine, and the mRNA levels of ADAM28 were evaluated by RT-PCR. The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells. The ADAM28 expression was also assessed in TCGA and GEO databases, and the results were confirmed in the collected tumor and adjacent normal tissues. The overall survival (OS) rate and relapse-free survival (RFS) rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter. Furthermore, the OS rate was calculated in pancreatic cancer patients with high tumor mutation burden (TMB) and low TMB. CCK-8 assay was used to examine the effect of ADAM28 on the viability of SW1990 cells. The ADAM28 and its co-expressed genes were analyzed in the cBioPortal for cancer genomics and subjected to GSEA pathway analysis. The correlations of ADAM28 with GSTP1, ABCC1, GSTM4, and BCL2 were analyzed based on TCGA data on pancreatic cancer. RESULTS RNA-sequence analysis identified that ADAM28 was overexpressed in gemcitabine-resistant cells, and gemcitabine treatment could induce the expression of ADAM28. The mRNA and protein levels of ADAM28 were elevated in gemcitabine-resistant SW1990 cells compared with parallel cells. Also, the expression of ADAM28 was upregulated in pancreatic tumor tissues against normal pancreatic tissues. Notably, ADAM28 was highly expressed in the classical type than in the basal tumor type. Furthermore, the high expression of ADAM28 was associated with low OS and RFS rates. Interestingly, the high levels of ADAM28 was associated with a significantly lower OS rate in the high TMB patients, but not in the low TMB patients. Moreover, overexpression of ADAM28 could reduce the cell viability inhibition by gemcitabine, and knockdown of ADAM28 could enhance the proliferation inhibition by gemcitabine. The GSEA analysis showed that ADAM28 was related to the regulation of drug metabolism, and ADAM28 was significantly positively correlated with GSTP1, ABCC1, GSTM4, and BCL2. CONCLUSION This study demonstrates that ADAM28 is overexpressed in pancreatic cancer, and closely involved in the regulation of gemcitabine resistance. Overexpression of ADAM28 is a novel prognostic biomarker in pancreatic cancer.

Purpose: To assess the clinical and radiographic outcomes of coronoid process fractures surgically managed with buttress plate fixation via a medial approach. Methods: A retrospective review of all coronoid fractures surgically fixed in our institution using a buttress plate technique via a medial approach between June 2012 and April 2015 by the senior author was performed. These fractures were all sizeable fractures contributing to persistent elbow instability in terrible triad or varus posteromedial rotatory instability injury patterns. A prospective telephone questionnaire was conducted to assess patient outcomes using the disabilities of the arm, shoulder and hand (DASH) score and Mayo hlbow performance score (MEPS). Results: Twelve patients were included in the study, comprising 10 males and 2 females with an average age of 39 years (range, 19-72 years). Mean follow-up was 16 months (range, 4-18 months). The average time to radiographic union was 4 months (range, 3-7 months). Range of motion measurements at final follow-up were obtained in 11 out of 12 patients, with one patient defaulting follow-up. All 11 patients displayed a functional elbow range of motion of at least 30°-130°, with an average arc of motion of 130° (range, 110°－140°), mean elbow flexion of 134° (range, 110°-140°) and mean flexion contracture of 3° (range, 0°-20°). The mean DASH score was 16 (range, 2.5-43.8) and the mean MEPS was 75 (range, 65-100). Complications observed included one patient with a superficial wound infection which resolved with a course of oral antibiotics and one patient with radiographic evidence of heterotopic ossification which was conservatively managed. No residual elbow instability was observed and no reoperations were performed. Conclusion: Buttress plate fixation via a medial approach of coronoid process fractures that contribute to persistent elbow instability represents a reliable method of treatment that produces satisfactory and predictable outcomes. Key words: Coronoid process; Anteromedial facet fracture; Complex elbow instability; Terrible triad injury

Lung cancer remains the leading cause of cancer-associated mortality in China and the world. Increasing numbers of studies have reported that sphingosine kinase 1 (SPK1) is frequently highly expressed in tumors of various origins, including lung cancer, and its high expression contributes toward tumor progression. However, the clinical significance of SPK1 and its role in the growth and metastasis of non-small-cell lung cancer (NSCLC) remain unclear. In the present study, we found that SPK1 expression was expressed highly in NSCLC tissues and cell lines. Knockdown of SPK1 suppressed cell growth, proliferation, migration, and invasion and increased apoptosis. Moreover, knocking down SPK1 expression inhibited the growth of tumors in nude mice. Mechanistically, silencing the expression of SPK1 inhibited the expression of p-extracellular signal-regulated kinase (ERK). Moreover, the ERK-specific inhibitor U0126 suppressed the expression of the epithelial-mesenchymal transition of lung cancer cells. Together, our findings indicated that SPK1 enhanced tumor growth in lung cancer and induced metastasis by activating the ERK1/2 signaling pathway, indicating its potential application in NSCLC diagnosis and therapy.

Anti-inflammatory and antipyretic analgesic western medicine chemicals such as aspirin and antibiotics have the potential to be illegally added into Guangdong herbal teas (GHT, Guangdong Liangcha) to enhance its efficacy. The present work reports firstly a ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method after HLB solid phase extraction (SPE) and purification for the simultaneous analysis of 8 chemical substances including aspirin, acetaminophen, chlortrimeton, diclofenac, cefradine, cefalexin, cefazolin and azithromycin illegally added into GHT. Supernatant was adjusted to pH 3–4 after high speed centrifugation of sample. It was subsequently extracted and purified in one step by HBL SPE. Eight target substances were separated on a C18 column by gradient elution with acetonitrile and 0.1% formic acid in water as mobile phase, scanned by dynamic switching of ESI positive ion mode and negative ion mode, detected with MS/MS in multiple reactions monitoring (MRM) mode and quantified by external standard method. The limit of detection, matrix effect, recovery and precision of the developed method were investigated. Results were linear in the concentration range of 1.0–200 μg/L for all analytes of interest, with R2 >0.999. Limits of detection (LOD) were in the range of 0.1–2.0 μg/kg. Matrix effects were in the range of 85–102%. Recoveries for negative samples at three spiked levels were between 80.2% and 103%, and the intra-day precision and inter-day precision were in the ranges of 3.1–9.0% and 4.7–11.8%, respectively. The method was successfully applied to analyze 8 western medicines chemicals in 36 GHT and 3 illegal chemical substances especially acetaminophen were detected in several Liangcha samples.

Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood–brain barrier. Our previous works show that bile duct ligation (BDL) impairs expression and function of brain BCRP in rats. Since zidovudine (AZT) is BCRP substrate, we investigated whether impaired expression and function of BCRP increased brain distribution and toxicity of AZT in BDL-D7 rats. After administration of AZT (10 mg/kg, i.v.), BDL markedly increased brain AZT concentrations, compared with sham-operated (SO) rats. The ratio of AZT brain-to-plasma area under concentration curve (AUC) in BDL rats was increased to 1.6-folds of SO rats. After treatment with AZT (100 mg/kg every day, i.v.) for 7 days, BDL significantly impaired cognitive functions compared with SO rats, evidenced by the significantly decreased percentage of alternation in Y-maze test and prolonged escaped latency in two-way passive avoidance trial. Furthermore, AZT treatment caused significant decrease in copies of mitochondrial DNA and mitochondrial membrane potential in hippocampus of BDL rats. Moreover, AZT treatment caused a significant decrease of cortex microtubule-associated protein 2 and hippocampus synaptophysin levels in BDL rats. AZT-induced CNS adverse alterations in BDL rats were not observed in SO rats treated with AZT. In conclusion, BDL decreases the function and expression of brain BCRP in rats, leading to increased brain distribution of AZT, which in turn enhances AZT CNS toxicity, leading to mitochondrial dysfunction, neuronal damage, and ultimately cognitive dysfunction.

Objective The relationships among sleep, circadian rhythm, and intensive care unit (ICU)-acquired delirium are complex and remain unclear. This study aimed to examine the pathophysiological mechanisms of sleep and circadian rhythm disturbances in patients with ICU-acquired delirium. Methods This study included critical adult patients aged 18 to 75 years who were treated in the ICU. Twenty-four-hour polysomnography was performed and serum melatonin and cortisol levels were measured six times during polysomnography. Receiver operating characteristic curves and binomial logistic regression were used to evaluate the potential of sleep, melatonin, and cortisol as indicators of delirium in the ICU. Results Patients with delirium (n = 24) showed less rapid eye movement (REM) sleep compared with patients without delirium (n = 24, controls). Melatonin levels were lower and cortisol levels were higher in the delirium group than in the control group. REM sleep, melatonin, and cortisol were significantly associated with delirium. The optimal cutoff values of REM sleep and mean melatonin and cortisol levels that predicted delirium were ≤1.05%, ≤422.09 pg/mL, and ≥212.14 ng/mL, respectively. Conclusions REM sleep, and melatonin and cortisol levels are significantly associated with the risk of ICU-acquired delirium. Improved sleep and readjustment of circadian rhythmicity may be therapeutic targets of ICU-acquired delirium.

16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. A number of studies have described microbial alterations corresponding to physical frailty and nursing home residence among aging individuals. A gut-muscle axis through which the microbiome influences skeletal muscle growth/function has been hypothesized. However, the microbiome has yet to be examined in sarcopenia. Here, we collected fecal samples of 60 healthy controls (CON) and 27 sarcopenic (Case)/possibly sarcopenic (preCase) individuals and analyzed the intestinal microbiota using 16S rRNA sequencing. We observed an overall reduction in microbial diversity in Case and preCase samples. The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium—known butyrate producers—were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired. In contrast, lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that sarcopenia is associated with a pro-inflammatory metagenome. These analyses demonstrate structural and functional alterations in the intestinal microbiota that may contribute to loss of skeletal muscle mass and function in sarcopenia.

Proper stroke posture and rhythm are crucial for kayakers to achieve perfect performance and avoid the occurrence of sport injuries. The traditional video-based analysis method has numerous limitations (e.g., site and occlusion). In this study, we propose a systematic approach for evaluating the training performance of kayakers based on the multiple sensors fusion technology. Kayakers&rsquo, motion information is collected by miniature inertial sensor nodes attached on the body. The extend Kalman filter (EKF) method is used for data fusion and updating human posture. After sensor calibration, the kayakers&rsquo, actions are reconstructed by rigid-body model. The quantitative kinematic analysis is carried out based on joint angles. Machine learning algorithms are used for differentiating the stroke cycle into different phases, including entry, pull, exit and recovery. The experiment shows that our method can provide comprehensive motion evaluation information under real on-water scenario, and the phase identification of kayaker&rsquo, s motions is up to 98% validated by videography method. The proposed approach can provide quantitative information for coaches and athletes, which can be used to improve the training effects.

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

Tetracycline antibiotics as the emerging pollutants had been drawn abroad increasing concerns. An agricultural waste, the lignocellulosic hazelnut shell, was used as the carbon source to prepare the nanocomposites of zero-valent iron@biochar by pyrolytic reduction method at 1123 K for 2 h in N2 atmosphere. The adsorptive removal of tetracycline, oxytetracycline and chlortetracycline by the zero-valent iron@biochar from aqueous solution was investigated by batch method. The optimal experimental conditions were found to be at pH 6–7 with a contact time of 40 min. The adsorbed amounts of oxytetracycline, chlortetracycline and tetracycline at 298 K were 52.7, 42.5 and 39.1 mg g−1, respectively. Adsorption process of three antibiotics by the nanocomposite pursued Langmuir and pseudo-second-order equations. Thermodynamic parameters illustrated that the adsorption was spontaneous and endothermic intrinsically. The high removal efficiencies up to 95% of the zero-valent iron@biochar for oxytetracycline and chlortetracycline from the culture wastewaters had opened the potential applications for the removal of the antibiotics.

Background: Sepsis coagulopathy or disseminated intravascular coagulation (DIC) mainly due to progressive endothelial disruption and damage. The glycocalyx is expressed on the endothelial cell surface and contributes to anti-thrombogenicity, anti-inflammatory, and regulates vascular permeability. We aimed to evaluate the clinical utility of plasma glycocalyx components as biomarkers in predicting the onset of DIC in sepsis. Materials and methods: This was a prospective observational study of 45 patients with sepsis (June to December 2018). Demographic, clinical (Acute Physiology, Age, Chronic Health Evaluation II [APACHE II], Sequential Organ Failure Assessment [SOFA]), and laboratory data from medical records were analyzed. Endothelial glycocalyx components (syndecan-1, heparan sulfate, hyaluronan) were measured using an ELISA kit. Results: Among the 45 patients (23, sepsis; 22, septic shock), plasma syndecan-1, heparan sulfate, and hyaluronan levels were higher in those with septic shock and were positively correlated with disease severity as determined by the APACHE II and SOFA scores and lactate levels. Receiver operating characteristic curve analysis revealed high sensitivity and specificity of syndecan-1 for predicting septic shock. Further, these levels were compared between patients with or without the development of DIC. Plasma syndecan-1 and hyaluronan levels were significantly elevated in patients with DIC compared to those in patients without DIC and were strongly associated with activated partial thromboplastin time, prothrombin time, and platelet counts. Area under the curve values for predicting DIC based on syndecan-1 and hyaluronan levels measurements were 0.774 and 0.740, respectively. Conclusions: Increased plasma syndecan-1 and hyaluronan levels may be indicators of disease severity and useful predictors for DIC development in sepsis.

The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel subset of in vivo Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and Soat1 activity synergistically reduces proliferation of mouse skin epithelial cells and of human skin and oral squamous cell carcinoma cultured lines. Varying Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1 levels, the inhibition of Scd1, or the addition of Scd1-product oleate, individually affects the plasma membrane organization (or fluidity) in mouse keratinocytes. These factors also affect the strength of signal transduction through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell proliferation and HFSC activation. Our working model is that HFSC factor Runx1 modulates the fatty acid production, which affects membrane organization, facilitating signal transduction for rapid proliferation of normal and cancer epithelial cells.

To investigate the effect of aggregate contact condition on the deformation stability of asphalt mixture (DSAM), computed tomography system was used to acquire a contact parameter of aggregates – t...

Background The prevalence of adverse food reactions in patients with chronic inhalant diseases has seldom been studied in China. This study is to investigate the prevalence of adverse food reactions and the symptoms caused in respiratory patients. Methods Respiratory patients in allergy clinics were asked to complete a questionnaire. Patients’ information such as age, gender, family history of allergy, and adverse reactions to a list of 48 foods and the symptoms caused, was recorded. Multivariate analyses were performed to determine the prevalence of adverse food reactions and their associated symptoms. Results 459 subjects, with an average age of 32 years old, completed the questionnaire; 45.3% were male. Among the 459 subjects, 38.1% (175/459) had an adverse reaction to food: 13.6% had an adverse food reaction to crab, 12.4% had an adverse food reaction to shrimp; and 9.9% had an adverse reaction to shellfish. Peach and nectarine were also shown to be common causative foods with 6.8% of the study group showing an adverse reaction to peach and 5.2% to nectarine. Seafood mainly caused skin symptoms and fruits gave rise to more throat, oral, and gastrointestinal problems. Conclusion The prevalence of adverse food reactions is high for patients with respiratory diseases. This indicates that adverse food reactions should be considered in the treatment and management of patients with chronic inhalant diseases. Electronic supplementary material The online version of this article (10.1186/s13223-017-0228-3) contains supplementary material, which is available to authorized users.

Background Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1’s capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. Methods The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. Results The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P = 0.035), high levels of serum AFP (P = 0.049), more frequency of node metastasis (P = 0.015), later TNM stage (P = 0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P = 0.021), while LC3B were suggested to be negatively related with patients’ PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P = 0.002) and shorter 5-year progression free survival (PFS)(P = 0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. Conclusion ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.

// Yan-Feng Zhen 1, * , Xing-Yu Liu 2, * , Dong-Hao Zhou 3, * , Xiangdong Du 4 , Guangzhong Yin 4 , Yingyang Zhang 4 , Hui Fang 1 , Gang Xu 5 , Jair C. Soares 6 and Xiang Yang Zhang 6 1 Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, China 2 Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, China 3 Department of Endocrinology, Linyi People’s Hospital, Linyi, China 4 Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China 5 Department of Burn, Tangshan Gongren Hospital, Tangshan, China 6 Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA * These authors contributed equally to this work Correspondence to: Hui Fang, email: fanghui@medmail.com.cn Xiang Yang Zhang, email: xiang.y.zhang@uth.tmc.edu Keywords: type 2 diabetes; brain-derived neurotrophic factor; cognition; polymorphism; association Received: August 05, 2017 Accepted: November 23, 2017 Published: December 16, 2017 ABSTRACT Background and aims: Type 2 diabetes (T2DM) is associated with cognitive deficits. However, their pathophysiological mechanisms are still unknown. Recent study suggests that brain-derived neurotrophic factor (BDNF) is correlated with cognitive deficits in T2DM patients. This study was to determine whether altered serum BDNF levels and cognitive deficits depended on the BDNF Val66Met polymorphism in T2DM. Results: The BDNF Val66Met polymorphism may not contribute directly to the susceptibility to T2DM. The total and nearly all index scores (all p 0.05) of RBANS were markedly decreased in T2DM compared with healthy controls. Serum BDNF levels were significantly lower in patients than that in controls ( p < 0.001), and BDNF was positively associated with delayed memory in patients ( p < 0.05). The Met variant was associated with worse delayed memory performance among T2DM patients but not among normal controls. Moreover, serum BDNF was positively associated with delayed memory among Met homozygote patients ( β = 0.29, t = 2.21, p = 0.033), while serum BDNF was negatively associated the RBANS total score ( β = –0.92, t = –3.40, p = 0.002) and language index ( β = −1.17, t = –3.54, p = 0.001) among Val homozygote T2DM patients. Conclusions: BDNF gene Val66Met variation may be associated with cognitive deficits in T2DM, especially with delayed memory. The association between lower BDNF serum levels and cognitive impairment in T2DM is dependent on the BDNF Val66Met polymorphism. Methods: We recruited 311 T2DM patients and 346 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), serum BDNF levels, and the BDNF Val66Met polymorphism.

Background We evaluated the possible relationships between serum total homocysteine and folate and Vitamin B12 in patients with intracranial aneurysm. Methods We enrolled consecutive patients with intracranial aneurysm from the Han population who were admitted to the hospital, as well as control subjects who received medical examination on an outpatient basis. The serum total homocysteine, folate, and Vitamin B12 levels were measured in patients with intracranial aneurysm and the control group, and the associations between those factors were analyzed using multivariate logistic analysis. Results A total of 140 patients with intracranial aneurysm and 140 control subjects were enrolled from July 2014 to December 2015. The mean serum total homocysteine level in the patient group (19.98 ± 10.84 µmol/L) was significantly higher than that in the control group (15.13 ± 5.55 µmol/L, P Conclusions The present study provides evidence regarding the association between serum total homocysteine and folate and Vitamin B12 in patients with intracranial aneurysm. Hyperhomocysteinemia is an independent risk factor for intracranial aneurysm, and folate and Vitamin B12 are protective against intracranial aneurysm due to their roles in regulating the metabolism of homocysteine.

A target molecule responsible for cell cycle arrest by metformin was discovered using a gene chip array in lung cancer cells and the effect of metformin on E2F8 was assessed. The siRNA-mediated knockdown of E2F8 significantly suppressed G1-S progression while ectopic expression of E2F8 relieved metformin-induced G1 arrest. The mRNA levels of p21 were found to be inversely related to those of E2F8 in lung cancer cells while siRNA-mediated knockdown of p21 partly rescued siE2F8-induced arrest of the cell cycle. Metformin had no effect on degradation of E2F8 mRNA. Activation and inhibition of AMPK by AICAR and Dorsomorphin, respectively, did not affect E2F8 suppression by metformin. The clinical significance of E2F8 was analyzed in The Cancer Genome Atlas (TCGA) data. One hundred six (13%) of 848 TCGA lung cancers overexpressed E2F8 mRNA. The overexpression of E2F8 was associated with poor overall survival (adjusted hazard ratio = 1.58, 95% confidence interval = 1.13–2.22; P = 0.008). The present study suggests that metformin may induce cell cycle arrest at the G1 phase by suppressing E2F8 expression in lung cancer cells. In addition, E2F8 may be associated with poor overall survival in lung cancer patients irrespective of histology.

Background The objective of this study is to investigate pharmacokinetics and dose regimens of cefquinome in black swans following intravenous (IV) and intramuscular (IM) administration at a single dose of 2 mg/kg. The MICs of cefquinome against 49 Escherichia coli isolates from black swans were determined. Monte Carlo simulation was applied to conduct the dose regimen assessment and optimization of cefquinome against E. coli in black swans, and a pharmacokinetic/pharmacodynamic (PK/PD) cutoff was established for E. coli isolates obtained in this study. Results The PK parameters of T1/2α (0.31 h), T1/2β (1.69 h) and ClB (0.13 L/kg·h) indicated a rapid distribution and elimination of cefquinome in black swans after IV administration. After IM injection, the corresponding PK parameters of T1/2Ka, T1/2Ke, Tmax, Cmax, and F were 0.12 h, 1.62 h, 0.39 h, 5.71 μg/mL and 74.2%, respectively. The MICs of cefquinome against black swans E. coli ranged from 0.03 to 8 μg/mL, with MIC50 and MIC90 of 0.06 and 0.5 μg/mL, respectively. The PK/PD cutoff of cefquinome against E. coli was determined to be 0.2 μg/mL. Monte Carlo simulation showed that the nominal dose regimen (2 mg/kg/24 h) could not achieve a satisfactory probability of target attainment (PTA) for %TMIC ≥ 50%, indicating a risk of treatment failure and the development of potential drug resistance. Conclusions The current daily dosage of cefquinome when divided into 12-h interval (1 mg/kg/12 h) may be effective for the treatment of E. coli infections with an MIC ≤0.5 μg/mL. Electronic supplementary material The online version of this article (doi:10.1186/s12917-017-1148-7) contains supplementary material, which is available to authorized users.