Rubusoside As a Multifunctional Stabilizer for Novel Nanocrystal-Based Solid Dispersions with a High Drug Loading: A Case Study.

The oral bioavailability of poorly soluble drugs has always been the focus of pharmaceutical researchers. We innovatively combined nanocrystal technology and solid dispersion technology to prepare novel nanocrystalline solid dispersions (NCSDs), which enable both the solidification and redispersion of nanocrystals, offering a promising new pathway for oral delivery of insoluble Chinese medicine ingredients. The rubusoside (Rub) was first used as the multifunctional stabilizer of novel apigenin nanocrystal-based solid dispersions (AP-NSD), improving the in vitro solubilization rate of the insoluble drug apigenin(AP). AP-NSD has been produced using a combination of homogenisation and spray-drying technology. The effects of stabilizer type and concentration on AP nanosuspensions (AP-NS) particles, span, and zeta potential were studied. And the effects of different types of protective agents on the yield and redispersibility of AP-NSD were also studied. Furthermore, AP-NSD was characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Solubility was used to assess the in vitro dissolution of AP-NSD relative to APIs and amorphous solid dispersions (AP-ASD), and AP-ASD was prepared by the solvent method. The results showed that 20% Rub stabilized AP-NSD exhibited high drug-loading and good redispersibility and stability, and higher in vitro dissolution rate, which may be related to the presence of Rub on surface of drug. Therefore provides a natural and safe option for the development of formulations for insoluble drugs.

Pre-transjugular-intrahepatic-portosystemic-shunt measurement of hepatic venous pressure gradient and its clinical application: A comparison study.

BACKGROUND: It is controversial whether transjugular intrahepatic portosystemic shunt (TIPS) placement can improve long-term survival. AIM: To assess whether TIPS placement improves survival in patients with hepatic-venous-pressure-gradient (HVPG) ≥ 16 mmHg, based on HVPG-related risk stratification. METHODS: Consecutive variceal bleeding patients treated with endoscopic therapy + nonselective ß-blockers (NSBBs) or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019. HVPG measurements were performed before therapy. The primary outcome was transplant-free survival; secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). RESULTS: A total of 184 patients were analyzed (mean age, 55.27 years ± 13.86, 107 males; 102 in the EVL+NSBB group, 82 in the covered TIPS group). Based on the HVPG-guided risk stratification, 70 patients had HVPG < 16 mmHg, and 114 patients had HVPG ≥ 16 mmHg. The median follow-up time of the cohort was 49.5 mo. There was no significant difference in transplant-free survival between the two treatment groups overall (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.35-1.05; P = 0.07). In the high-HVPG tier, transplant-free survival was higher in the TIPS group (HR, 0.44; 95%CI: 0.23-0.85; P = 0.004). In the low-HVPG tier, transplant-free survival after the two treatments was similar (HR, 0.86; 95%CI: 0.33-0.23; P = 0.74). Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier (P < 0.001). The difference in OHE between the two groups was not statistically significant (P = 0.09; P = 0.48). CONCLUSION: TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

Effect of molecular distillation on the anti-inflammatory activity and neurotoxicity of Asarum essential oil.

Asarum essential oil (AEO) has been shown to have good pharmacological activities for the anti-inflammatory and analgesic effects, but increasing the dose may cause toxicity. Therefore, we studied the toxic and pharmacodynamic components of AEO by molecular distillation (MD). Anti-inflammatory activity was assessed using RAW264.7 cells. Neurotoxicity was assessed in PC12 cells and the overall toxicity of AEO was evaluated in the mouse acute toxicity assay. The results showed that AEO is primarily composed of safrole, methyl eugenol, and 3,5-dimethoxytoluene. After MD, three fractions were obtained and contained different proportions of volatile compounds relative to the original oil. The heavy fraction had high concentrations of safrole and methyl eugenol, while the light fraction contained high concentrations of α-pinene and ß- pinene. The original oil and all three fractions exhibited anti-inflammatory effects, but the light fraction demonstrated more excellent anti-inflammatory activity than the other fractions. Asarum virgin oil and MD products are all neurotoxic. The exposure of PC12 cells to high concentrations of AEO resulted in abnormal nuclei, an increased number of apoptotic cells, increased ROS formation, and decreased SOD levels. Moreover, the results of acute toxicity tests in mice revealed that the light fractions were less toxic than virgin oils and other fractions. In summary, the data suggest that the MD technology enables the enrichment and separation of essential oil components and contributes to the selection of safe concentrations of AEO.

Curculigoside Represses the Proliferation and Metastasis of Osteosarcoma via the JAK/STAT and NF-κB Signaling Pathways.

Curculigoside (Cur) is a natural component from Curculigo orchioides Gaertn, with various bioactivities. The function of Cur in the nervous system and osteoarthritis has been reported. However, its role in osteosarcoma (OS) needs to be investigated. Hence, we focus on probing the impact of Cur on OS. In vitro, cell counting kit 8 (CCK-8), flow cytometry and Transwell assay were used to investigate the effects of Cur on OS cell proliferation, apoptosis, migration and invasion. In vivo, we developed a xenograft model to figure out the effect of Cur on tumor growth in nude mice. Western blotting (WB) was conducted to compare the levels of Cur on apoptosis-related proteins (C-caspase-3, Bax, and Bcl-2), epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin, Snail, and E-cadherin) and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and nuclear factor-κB (NF-κB) pathways in vitro and in vivo. In-vitro data testified that Cur treatment markedly hampered OS cells' growth, migration and invasion and intensified their apoptosis compared to that of the control group. In vivo, Cur treatment notably hampered the growth of OS tumors in mice. In addition, both in vitro and in vivo experiments demonstrated that the phosphorylation of JAK2, STAT3, and NF-κB were inhibited through Cur treatment. Furthermore, the inhibition of Cur in OS cells was demonstrated by up-regulating the expression of JAK/STAT and NF-κB pathways protein levels. In summary, the data suggest that Cur curbs OS growth by down-regulating the JAK/STAT and NF-κB pathways, which is an underlying therapeutic option for OS treatment.

Number of endoscopic sessions to eradicate varices identifies high risk of rebleeding in cirrhotic patients.

BACKGROUND AND AIMS: Risk stratification to identify patients with high risk of variceal rebleeding is particularly important in patients with decompensated cirrhosis. In clinical practice, eliminating gastroesphageal varices thoroughly after sequential endoscopic treatment reduces the rebleeding rate, however, no simple method has been build to predict high risk of variceal rebleeding. We conducted this study to explore the value of the number of endoscopic sessions required to eradicate gastroesphageal varices in identifying high risk of rebleeding. PATIENTS AND METHODS: Consecutive cirrhotic patients received sequential endoscopic therapy between January 2015 and March 2020 were enrolled. Endoscopic treatment was performed every 1-4 weeks until the eradication of varices. The primary endpoint was variceal rebleeding. RESULTS: A total of 146 patients were included of which 60 patients received standard therapy and 86 patients underwent sequential endoscopic treatment alone. The cut-off value of the number of sequential endoscopic sessions is 3.5 times. Variceal rebleeding was significant higher in patients with endoscopic sessions > 3 times versus ≤ 3 times (61.5% vs. 17.5%, p < 0.001). Variceal rebleeding of patients with endoscopic sessions ≤ 3 times was significant lower than patients with > 3 times in group of standard therapy (19.6% vs. 88.9%, p < 0.001) and endoscopic therapy (15.9% vs. 47.1%, p = 0.028) respectively. CONCLUSION: The number of sequential endoscopic sessions required to eradicate the varices is related to the risk of variceal rebleeding in patients with cirrhosis. If three times of endoscopic treatment can not eradicate the varices, a more aggressive treatment such as TIPS should be seriously considered.

Relationship between subclasses low-density lipoprotein and carotid plaque.

Backgound: Low-density lipoprotein (LDL) cholesterol can lead to the occurrence of atherosclerotic plaques, but patients with normal LDL still have atherosclerotic plaques in clinical practice. With the proposal of LDL subclass, this experiment investigated the relationship between the LDL content of different subclasses and the stability of carotid plaques. Methods: Plaque stability was suggested by carotid ultrasound results. 37 patients with stable plaques were classified into one group and 41 patients with unstable plaques were classified into another group. The data of age, glycosylated hemoglobin (Ghb), and homocysteine (Hcy) were collected. The contents of LDL subclasses were measured by LIPOPRINT system. The data of total cholesterol (TC), LDL cholesterol, and triglyceride (TG) were collected. The plaque stability was assessed by carotid artery color Doppler ultrasound and the intima-media thickness (IMT) was measured. Results: The levels of LDL-1 subclass 19.00 (13.00, 27.50) and LDL-2 subclass (21.62 ± 7.24) in the stable plaque group were higher than those in the unstable plaque group (p < 0.05). The levels of LDL-3 subclass (12.24 ± 4.58), LDL-4 subclass 5.00 (2.00, 9.00), and sd-LDL 0 (0.00, 3.00) in the unstable plaque group were higher than those in the stable plaque group (p < 0.05). LDL-1 subclass (adjusted OR = 0.923 and p < 0.05), and LDL-3 subclass (adjusted OR = 1.176 and p < 0.05) were independent risk factors for plaque stability. Conclusion: Elevated LDL1 is associated with stable plaques whereas LDL3 was found associated with unstable plaques.

Increase in Free Hepatic Venous Pressure Response to Beta-Blockers Predicts Variceal Bleeding in Cirrhotic Patients.

BACKGROUND AND AIMS: Nonselective beta-blockers (NSBBs) are the main drug to prevent portal hypertension. It could alter free hepatic venous pressure (FHVP); however, the significance is unknown. This prospective study was to explore the change of FHVP after use of NSBBs and its predictive value for gastroesophageal varices (GOV) bleeding in cirrhotic patients. Patients and Methods. Cirrhotic patients with medium-large GOV between September 2014 and January 2019 were enrolled. After initial hepatic venous pressure gradient (HVPG) measurement, patients received oral NSBBs. Seven days later, the secondary HVPG was examined to evaluate the FHVP alteration and hemodynamic response. The variceal bleeding between patients with FHVP increased and decreased/unchanged was compared. RESULTS: A total of 74 patients were enrolled, and 62 patients completed the secondary HVPG measurement and was followed up. The cumulative bleeding rate was significantly higher in patients with FHVP increased ≥ 1.75 mmHg than those with FHVP decreased/unchanged (54.5% vs. 22.5%, p = 0.021), while there was no significant difference in bleeding between HVPG responders and nonresponders (32.6% vs. 37.5%, p = 0.520). For HVPG responders, variceal bleeding in patients with FHVP increased ≥ 1.75 mmHg was significantly more than that in patients with FHVP decreased/unchanged (57.9% vs. 28.6%, p = 0.041). Cox regression analysis showed that change of FHVP was an independent predictor of variceal bleeding. CONCLUSION: Increase ≥ 1.75 mmHg in FHVP responding to beta-blockers in cirrhotic patients with GOV indicates high risk of variceal bleeding. Besides HVPG response, change of FHVP should also be valued in hemodynamic evaluation to beta-blockers. This trial is registered with Chinese Clinical Trial Registry ChiCTR-IPR-17012836.

Tailor-made deep eutectic solvents extraction combined with UPLC-MS/MS determination of icarrin and icarisid II in rat plasma and its comparative pharmacokinetic application.

Using green and high efficient solvents to extract and trace active ingredients of traditional Chinese medicine (TCM) in the complex biological samples was still challenging. In this paper, a co-friendly, fast pretreatment method with high extraction efficiency, based on the tailor-made deep eutectic solvent (DES) system, combined with ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination of icarrin and icarisid II in rat plasma samples, which can be further applied to comparative pharmacokinetic studies after oral administration of Herba Epimedii and icarrin monomer in rats, respectively. PrE (l-proline: ethylene glycol = 1:4 mol/mol) and acetonitrile were optimized and combined as the tailor-made DES at the volumetric ratio of 3:7 to extract icarrin and icarisid II, and to precipitate the protein in rat plasma in one step simultaneously. The extraction efficiency of the tailor-made DES was about 1.7 times of DES (PrE). The extraction recovery of icarrin and icarisid II in rat plasma samples by this method were within the range of 90-110 %, and the lower limits of quantification (LLOQ) were 0.32 ng mL-1 (icarrin) and 0.43 ng mL-1 (icarisid II). There was a linear relationship between 0.32-80.16 ng mL-1 (icarrin) and 0.43-107.4 ng mL-1 (icarisid II), which effectively reduced the detection limit. In this comparative pharmacokinetic study, the maximum plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC0-∞) of two analytes in rat plasma of Herba Epimedii group were both much higher than those in the icarrin monomer group, which suggested that other ingredients in Herba Epimedii may contribute to the in vivo absorption of icarrin and icarisid II. This simple, rapid, relatively green and high effeicient method would provide a new approach for the extraction of active ingredients from complex biological samples.

Remediation and improvement of 2,4-dichlorophenol contaminated soil by biochar-immobilized laccase.

In this paper, laccase was immobilized with the adsorption-crosslinking method in which biochar was used as the carrier and glutaraldehyde was used as the crosslinking agent. Firstly, the optimal immobilization conditions and optimal operating conditions were investigated, and then the stability of both free laccase and immobilized laccase was compared. Finally, the 2,4-dichlorophenol contaminated soil was remedied with both free laccase and immobilized laccase, and the improvement on the remediation of the contaminated soil by immobilized laccase was analysed through the ecological evaluation. The results showed that in the optimal immobilization condition, the biochar with a particle size of 30 mesh should be selected, and glutaraldehyde with a volume fraction of 4% and 20 mL of laccase solution should be added to complete the 6-hour adsorption operation and 4-hour crosslinking operation. The stability of immobilized laccase was better than that of free laccase, and the thermal deactivation kinetic equation for the free laccase was lnA = -0.7657t + 0.4344 and the thermal deactivation kinetic equation for the immobilized laccase was lnA = -0.1048t + 0.0608, respectively. The degradation ability of immobilized laccase for 2-4 dichlorophenol was better than that of free laccase. The degradation rate of 2,4-dichlorophenol was 44.4% in the free laccase group and 64.6% in the immobilized laccase group. The ecological evaluation showed that the biochar-immobilized laccase had a positive effect on the soil ecological environment in the remediation process of the soil and can improve the remediation of the contaminated soil to some extent.

Degradation of 2,4-dichlorophenol contaminated soil by ultrasound-enhanced laccase.

In this paper, ultrasound was used to enhance the degradation effect of laccase for 2,4-dichlorophenol (2,4-DCP) in soil. The degradation effect and mechanism of the ultrasound-enhanced laccase were investigated. From the results, the degradation rate of 2,4-DCP can reach as high as 51.7% under the following conditions: reaction period was 21 h, pH = 5.5, ultrasound power was 240 W, duty cycle was 50%, and moisture content was 50%. Using the ultrasound-enhanced laccase, the degradation rate of 2,4-DCP was significantly higher than that using only laccase or only ultrasound. In addition, when ultrasound was used, the optimum pH for the degradation of 2,4-DCP using laccase was increased, making the degradation technology more practical. The analysis results from high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) revealed the degradation pathway of 2,4-DCP in soil: first, 2,4-DCP gradually became phenol through dechlorination, then the small molecular organic matter was generated from the hydroxyl radical or laccase reaction.

Endoscopic therapy + ß-blocker vs. covered transjugular intrahepatic portosystemic shunt for prevention of variceal rebleeding in cirrhotic patients with hepatic venous pressure gradient ≥16 mmHg.

BACKGROUND AND OBJECTIVE: Currently, monitoring hepatic venous pressure gradient (HVPG) have been proved to be the best predictor for the risk of variceal bleeding. We performed the study to evaluate the effect of endoscopic therapy + ß-blocker vs. covered transjugular intrahepatic portosystemic shunt (TIPS) for the prevention of variceal rebleeding in cirrhotic patients with HVPG ≥16 mmHg. METHODS: Consecutive cirrhotic patients with HVPG ≥16 mmHg treated with endoscopic therapy + ß-blocker or covered TIPS for variceal bleeding were retrospectively gathered between April 2013 and December 2018. The variceal rebleeding rate, survival, and incidence of overt hepatic encephalopathy (OHE) were compared. RESULTS: A total of 83 patients were analyzed, of which 46 received endoscopic therapy + ß-blocker and 37 covered TIPS. During a median follow-up of 12.0 months, the rebleeding rate (32.6 vs. 10.8%, P = 0.017) and rate of OHE (2.2 vs. 27.0%, P = 0.001) showed significant differences between the two groups, while liver transplantation-free survival (93.5 vs. 94.6%, P = 0.801) was similar. Preoperative and postoperative Child-Turcotte-Pugh scores were similar in either group. In addition, no significant differences of rebleeding rate (25.0 vs. 21.3%, P = 0.484) and survival (97.2 vs. 91.5%, P = 0.282) were observed between patients with 16 mmHg ≤ HVPG < 20 mmHg and HVPG ≥ 20 mmHg. CONCLUSION: Covered TIPS was more effective than endoscopic therapy + ß-blocker in preventing rebleeding in patients with HVPG ≥16 mmHg but did not improve survival. TIPS also induce more OHE.

Spleen Stiffness Predicts Survival after Transjugular Intrahepatic Portosystemic Shunt in Cirrhotic Patients.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications. Little is known about the ability of spleen stiffness (SS) for predicting the survival of cirrhotic patients undergoing TIPS. This study is to evaluate the influence of SS detected by point shear wave elastography (pSWE) in predicting survival after TIPS. METHODS: This retrospective cohort study screened consecutive patients who underwent TIPS and reliable pSWE measurement between October 2014 and September 2017 from our prospectively maintained database. SS values were measured before TIPS. The primary endpoint was the overall survival after TIPS. The Cox regression analysis model was used for univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to calculate the sensitivity, specificity, and positive and negative predictive values. RESULTS: A total of 89 patients were involved in the final analysis. 24 patients (27.0%) died during a median follow-up time of 31 m. Multivariable Cox regression analysis confirmed that higher SS value (P < 0.001), LS value (P = 0.008), diameter of shunt (P = 0.001), and older age (P < 0.001) were independent prognostic factors of survival after TIPS. The risk of death rose 57.440-fold for each SS unit (m/s) increase. SS was also correlated with liver failure after TIPS. ROC analysis showed that the best SS cutoff value was 3.60 m/s for predicting survival, with a sensitivity of 54.2% and specificity of 90.8%. CONCLUSIONS: The SS value determined by pSWE in cirrhotic patients was an independent predictive factor for survival after TIPS.

A nomogram to predict the risk of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in Cirrhotic Patients.

BACKGROUND AND AIM: Hepatic encephalopathy (HE) is a serious complication of decompensated liver cirrhosis, affecting the prognosis of patients underwent transjugular intrahepatic portosystemic shunts (TIPS). We aim to create a nomogram to predict hepatic encephalopathy- free survivals (HEFS) after TIPS in cirrhotic patients and select appropriate candidates for TIPS. METHODS: Cirrhotic patients underwent TIPS from 2015 to 2018 in our department were included. Multivariable Cox regression was conducted to estimate the predictors of overt HE (OHE) after TIPS within one year. A nomogram based on the Cox proportional hazard model using data from a retrospective training cohort (70% of the patients) was developed. Then the prediction model was validated in the remaining 30% patients by Harrell's C-indexes, ROC curves and calibration plots. RESULTS: Of 373 patients, 117 developed postoperative OHE (31.4%). The training and validation groups comprised 83 (31.4%) and 34 (31.2%) patients, respectively. The cumulative survival rates of patients with HE at 1, 2 and 3 years were 90%, 83% and 76%, respectively. The nomogram included the following variables: age, Child-Turcotte-Pugh class (CTP class), diabetes mellitus (DM), serum creatinine and serum sodium (C-index = 0.772). The C-index for HEFS prediction was 0.773 for the validation cohort. The ROC for predicting HEFS was 0.809 and 0.783, respectively. CONCLUSIONS: We created a nomogram of predicting postoperative HEFS in cirrhotic patients received TIPS. This nomogram could be an important tool of HE risk prediction before TIPS to guide the therapeutic strategy in cirrhotic patients.

Migration of heavy metals and migration-degradation of phenanthrene in soil using electro kinetic-laccase combined remediation system.

In order to solve the problem of heavy metal-organic compound soil pollution, in this paper, we developed a highly efficient electro kinetic-laccase combined remediation (EKLCR) system. The results showed that the EKLCR system had an obvious migration effect on heavy metals (copper and cadmium) and good migration-degradation effect on phenanthrene. The migration rates of copper and cadmium were 48.3% and 40.3%, respectively. Especially, with the presence of laccase, the removal rate of phenanthrene on Cu2+-contaminated soil was higher than that of Cd2+-contaminated soil due to the significant effect of heavy metals on the enzymatic activity of laccase. The average migration-degradation rate of phenanthrene by EKLCR system was 45.4%. Finally, gas chromatography-mass spectrometry (GC/MS) was used to analyze the degradation intermediates of phenanthrene in the soil, which included 9,10-Phenanthrenequinone, phthalic acid, and 2,2-Biphenyldicarboxylic Acid. In addition, we give the possible degradation pathways of phenanthrene, 2,2-Biphenyldicarboxylic Acid is further degraded to produce phthalic acid. The products of the phthalic acid metabolic pathway are protocatechuic acid, pyruvic acid or succinic acid, the final products of these organic acids are carbon dioxide and water.

Deep eutectic solvent combined with ultrasound-assisted extraction as high efficient extractive media for extraction and quality evaluation of Herba Epimedii.

Deep eutectic solvent (DES) combined with ultrasound-assisted extraction (UAE) was successfully developed and fully validated to simultaneously determine Icarrin, IcarisidⅡ, Epimcdin A, Epimcdin B and Epimcdin C for the quality evaluation of Herba Epimedii. Twelve kinds of DESs were initially screened, and then the effective extraction was achieved by the tailor-made DES consisting of the mixture of l-proline and ethylene glycol with the molar ratio of 1:4 in this study. The optimal conditions were further optimized by the orthogonal experimental design (OED). 0.2 g sample powder was ultrasonic extracted by using 4.00 mL of aqueous solution containing 70 % (v/v) the above DES for 45 min, resulting to the optimum extraction efficiency. The FT-IR and NMR spectra showed the chemical structural characteristic correlation between l-proline and ethylene glycol, and could infer the formation of hydrogen bonds between the hydroxyl group of ethylene glycol and the nitrogen atom of l-proline. The hierarchical cluster analysis (HCA) was further processed for the quality evaluation of Herba Epimedii. Finally, DES could be used to distinguish different origins and different kinds of Herba Epimedii, and to evaluate the quality of Herba Epimedii. This method provided good linearity, precision and accuracy. The recoveries of the five main bioactive flavonoids in Herba Epimedii were within the range of 88.5-107.7 % (RSD less than 3.4 %). Compared to the traditional extraction method of Icarin in the Chinese Pharmacopoeia (2015 edition), the solvent consumption was decreased by 80 % and the extraction time was shortened by 25 %, leading to more efficient and more convenient of this DES-UAE method. This work indicated that DES would be a promising high effective solvent for the analytical sample preparations of plant herbs, and it might have a broad application in the quality control of traditional Chinese medicines.

Sequential release of drugs form a dual-delivery system based on pH-responsive nanofibrous mats towards wound care.

Using Chitosan/PEO as the shell and PCL as the core, chitosan-polyethylene oxide/polycaprolactone nanofibrous mats were prepared successfully by coaxial electrospinning for co-load and sequential co-delivery of two drugs. Herein, lidocaine hydrochloride (Lid), used for pain relief, was added to the shell, and curcumin (Cur), an anti-inflammatory agent, was introduced into the core. Sodium bicarbonate (SB) was also added to the core layer to provide wound microenvironment sensitivity. Under acidic conditions, Lid was released due to the formation of -NH3+ by protonation of -NH2 on the chitosan molecular chains. At the same time, SB reacted with hydrogen ions to generate CO2, and many holes were generated on the surface of the fibers, providing more discharge paths for Cur release. Additionally, both Lid in the shell layer and Cur in the core layer exhibited acidic pH (∼5.4)-responsive release profiles. Moreover, a rapid release of Lid and a sustained release of Cur were observed to provide the immediate effects of analgesia and long-term antibacterial activity in the process of wound healing. Furthermore, after 48 h incubation, the mats showed continuous and excellent antibacterial performance against E. coli and S. aureus. The results of blood coagulation showed that the mats could achieve rapid hemostasis in the early stage of wound formation. Hemolytic and cytotoxicity evaluation also revealed that the mats had excellent hemocompatibility and cytocompatibility. Therefore, this study has made invaluable contributions to the design of a dual-drug-loaded dressing with microenvironment-responsive and sequential release properties towards wound care.

Prevalence and risk factors for postoperative delirium in patients with colorectal carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Postoperative delirium (POD) is a common, but severe complication in elderly patients undergoing surgery for colorectal cancer, but the prevalence and potential risk factors for POD were not well established. Therefore, a meta-analysis was preformed to clarify the prevalence and risk factors of POD in patients undergoing surgery for colorectal cancer. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched on August 2019. Studies were included if they reported the prevalence and risk factors of POD in patients undergoing colorectal cancer surgery. The guidelines for critically appraising studies of prevalence or incidence of a health problem were used to assess the quality of included studies. Pooled odds ratios (ORs) for individual risk factors were estimated using the Mantel-Haenszel methods in random effect model. Sensitive analyses based on different inclusion criteria were conducted to explore whether the current meta-analysis was enough credible and robust. RESULTS: Seventeen studies totaling 4472 patients undergoing colorectal cancer surgery were included. The pooled prevalence of POD is 14% (95% CI = 12-17%). Twelve significant risk factors were identified in pooled analysis including older age (OR = 1.10), sex (OR = 1.87), history of psychiatric disease (OR = 6.47), comorbidities (OR = 2.17), prognostic nutritional index (OR = 1.12), physical status (OR = 1.27), American Society of Anesthesiologists Score (ASA Scores) (OR = 1.65), history of alcohol abuse (OR = 2.23), postoperative pain management (OR = 1.91), perioperative blood transfusion (OR = 2.37), cognitive status (OR = 1.91), and lower serum level of albumin (OR = 0.58). CONCLUSIONS: POD is a frequent complication in patients undergoing surgery with colorectal cancer. Several risk factors including history of psychiatric disease, transfusion, comorbidities, male gender, and old age were significant predictors for POD.

TWEAK promotes hepatic stellate cell migration through activating EGFR/Src and PI3K/AKT pathways.

Activated human hepatic stellate cells (HSCs) showed enhanced ability of migration compared with quiescent HSCs, which is pivotal in liver fibrogenesis. The aim of the present study was to investigate the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on the migration of activated HSCs and to explore the relevant potential mechanisms. Human HSCs LX-2 cells were cultured with TWEAK. TNFRSF12A-downexpressing lentiviruses were used to infect LX-2 cells. The specific matrix metalloproteinases inhibitor BB94, the Src family kinase inhibitor, Dasatinib, and the specific inhibitor of phosphoinositide 3-kinase (PI3K), LY294002 were used to treat LX-2 cells combined with TWEAK. Cell migration and invasion was tested by the transwell assay. The expression of EGFR/Src, PI3K/AKT, and matrix metallopeptidase 9 (MMP9) was identified by real-time polymerase chain reaction or western blotting. The result showed TWEAK promoted HSC migration and collagen production. BB94 significantly attenuated the migration of LX-2 induced by TWEAK. Dasatinib inhibited the ability of cell migration stimulated by TWEAK. TWEAK upregulated the phosphorylation of epidermal growth factor receptor (EGFR) and Src. The phosphorylation of PI3K and AKT was significantly activated by TWEAK stimulation. Inhibition of PI3K/AKT reduced the expression of MMP9 induced by TWEAK. The present study, for the first time, demonstrated that TWEAK promoted HSC migration through the activation of EGFR/Src and PI3K/AKT pathways, and showed a novel potential mechanism of HSC migration regulated by TWEAK.

Influence of Vegetation Coverage and Climate Environment on Soil Organic Carbon in the Qilian Mountains.

Studying the spatial distribution pattern of soil organic carbon and its influencing factors is essential for understanding the carbon cycle in terrestrial ecosystems. Soil samples from four active layers of typical vegetation types (Populus, subalpine shrubs, Picea crassifolia Kom, and alpine meadow) in the upper reaches of Shiyang River basin in the Qilian Mountains were collected to determine the soil organic carbon content and physicochemical properties. The results show the following: (1) There are significant differences in the vertical distribution of Soil organic carbon in the watershed, and the Soil organic carbon content decreases significantly with increasing soil depth. (2) Mainly affected by biomass, the organic carbon content of different vegetation types in different soil layers is as follows: Alpine meadow > Picea crassifolia Kom > Populus > Subalpine shrub, and the soil organic carbon content increases with increasing altitude. Under different vegetation types, the Soil organic content is the highest in the 0-30 cm soil profile, and the maximum value often appears in the 0-10 cm layer, then gradually decreases downward. (3) When soil organic carbon is determined in different vegetation types in the study area, the change of hydrothermal factors has little effect on soil organic carbon content in the short term.

Comparison of transjugular intrahepatic portosystemic shunt for treatment of variceal bleeding in patients with cirrhosis with or without spontaneous portosystemic shunt.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications in cirrhosis. Spontaneous portosystemic shunts (SPSSs) may increase the risk of post-TIPS complications and mortality. This study was done to evaluate the safety and efficacy of TIPS for treating variceal bleeding between patients with and without SPSSs. PATIENTS AND METHODS: The clinical data of 467 consecutive patients with cirrhosis who received TIPS for variceal bleeding from January 2012 to January 2018 were screened. A total of 33 patients with coexisting SPSSs were included as the SPSS group, and 33 patients without SPSSs were randomly selected as control. The procedure-related complications and long-term outcomes were compared between the two groups. RESULTS: Both groups were successfully treated with TIPS. SPSSs were antegradely embolized before TIPS placement. In terms of safety, one patient in the SPSS group experienced an asymptomatic pulmonary embolism, and another patient experienced serious gastric ulcer bleeding. Overall, 23 (70.0%) patients in the SPSS group and 16 (51.5%) patients in the control group experienced different mild complications (P=0.131). During a median follow-up of more than 2 years, the rebleeding rates (7.1 vs. 3.7% at 1 year, P=0.508), overt hepatic encephalopathy occurrence rates (34.4 vs. 39.4% at 2 years, P=0.685), and orthotopic liver transplantation-free survival rates (73.2 vs. 70.7% at 2 years, P=0.557) were not significantly different between the two groups. CONCLUSION: TIPS combined with antegrade embolization is safe, effective, and feasible for patients with SPSSs, with safety and long-term outcomes comparable to patients without SPSSs.