Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis.

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1ß induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.

Integrated Health Maintenance Reminders for Improved HPV Vaccine Administration: Toward Improvements in Completion Disparities.

OBJECTIVE: To evaluate the effect of a health maintenance reminder (HMR) on human papillomavirus (HPV) vaccine administration and completion across different age, insurance, and race cohorts. STUDY DESIGN: Retrospective pre-post analysis. SETTING: Academic primary care. METHODS: Patients aged 9 to 26 who had initiated the HPV vaccine series from 2016 to 2021 were analyzed, based on current age-based standards. The cohort was divided based on vaccine uptake before and after the implementation of the HMR program in February 2020. The multivariate analysis estimated the odds of vaccine completion based on sociodemographic factors, and variable interactions were investigated to determine independent associations between sociodemographic factors and HMR implementation. RESULTS: There were 7654 individual patients (mean age was 15.8 years; 46.7 were males; and 50.7% were white). HPV vaccine completion rates increased post-HMR implementation by 59.2% (37% pre-, and 58.9% post-HMR; p < .001) in the entire cohort. Overall, black patients (adjusted odds ratio [aOR] = 0.68; 95% confidence interval [CI]: 0.60, 0.70) and patients ≥18 years (aOR = 0.13; 95% CI: 0.11, 0.15) were significantly less likely to complete their vaccine series; however, this improved significantly following HMR in these groups (p < .001). Post-HMR, race, and insurance status were not independently associated with disparate vaccine completion rates, however, age was, and patients ≤14 or younger had higher odds of vaccine completion (aOR = 3.54; 95% CI: 2.91, 4.32). CONCLUSION: The implementation of an HMR was associated with increased HPV vaccine uptake across age and race groups in this single-institution study. Future research should explore barriers to implementing HMRs in different health care settings.

The Effect of Chinese Herbal Medicine on Traumatic Anosmia: A Prospective, Randomized Clinical Trial.

OBJECTIVE: Chinese herbal medicine (CHM) has been implemented as a form of treatment for olfactory dysfunction. In this study, we aimed to use a tailored Guizhi decoction for the treatment of traumatic olfactory dysfunction. METHODS: Patients who had lost olfactory function after experiencing head trauma and whose olfactory function was anosmic were selected. The eligible patients were randomly assigned to two groups. In the CHM group, a tailored Guizhi decoction was prescribed, with patients also undergoing olfactory training (OT). In the OT group, patients performed OT only. The olfactory function of each patient was evaluated by both the phenyl ethyl alcohol (PEA) odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (TC-UPSIT), at both 3 and 6 months after the completion of treatment. RESULTS: A total of 38 patients in the CHM group and 40 in the OT group completed the study. The TC-UPSIT scores of patients slightly rose after treatment in both the CHM and OT groups. Nevertheless, there were no significant differences in TC-UPSIT scores before and after treatment in both groups. However, the PEA thresholds improved significantly in both CHM and OT groups (p = 0.005 and 0.016, respectively). Of note, there were no significant differences in threshold or identification scores between the CHM and OT groups. CONCLUSION: Our results show that adding a tailored Guizhi decoction to OT conferred a limited benefit to the olfactory function of patients experiencing traumatic anosmia. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:1473-1479, 2023.

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). METHODS: This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. RESULTS: The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. CONCLUSION: Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).

Tongue Acupuncture for the Treatment of Poststroke Aphasia: A Systematic Review and Meta-Analysis.

Objective: This review evaluated the efficacy of tongue acupuncture for the clinical treatment of poststroke aphasia. Methods: PubMed, Medline, Cochrane, Embase, CNKI, VIP, and Wanfang databases were searched from their inception to 1st June 2022. The dataset included randomized controlled trials (RCTs) with tongue acupuncture for the treatment of poststroke aphasia. Data aggregation and risk of bias evaluation were conducted on Review Manager Version 5.4.1 and Stata16.0. The main outcome measures included the Aphasia Battery of Chinese (ABC), the Chinese Functional Communication Profile (CFCP), the Boston Diagnostic Aphasia Examination (BDAE), and clinical efficiency. Then, comparing the effectiveness of tongue acupuncture, tongue acupuncture combined with conventional therapies, conventional therapies with head acupuncture, language training, body acupuncture, and Jie Yu Dan. Results: A total of 20 studies with 1355 patients were included. Meta-analysis showed that compared with conventional treatments, tongue acupuncture has a significant improvement in clinical efficacy score (MD = 1.25, 95% CI (1.09, 1.43), P=0.001) and CFCP of poststroke aphasia (MD = 39.78, 95% CI (26.59, 52.97), P < 0.00001), but was not significant in improving ABC (MD = 5.95, 95% CI (2.85, 9.04), P=0.06). Compared to the conventional treatments, tongue acupuncture combined with conventional therapies promoted the ABC (MD = 11.48, 95% CI (2.20, 20.75), P < 0.00001), clinical efficacy score (MD = 1.22, 95% CI (1.14, 1.30), P < 0.00001), and CFCP score (MD = 29.80, 95% CI (19.08, 40.52), P < 0.00001) of poststroke aphasia. Conclusion: This systematic review indicated that tongue acupuncture or tongue acupuncture combined with conventional treatments was an effective therapy for treating poststroke aphasia. However, stricter evaluation standards and rigorously designed RCTs are needed.

Effects of dietary supplement with a Chinese herbal mixture on growth performance, antioxidant capacity, and gut microbiota in weaned pigs.

Weaning stress decreases the growth performance of piglets and is one of the main concerns of pig industries. Traditional Chinese herbal medicines have been used to reduce the adverse effects of weaning stress as both nutritional supplements and antibiotic substitutes. This study aimed to evaluate the effects of a Chinese herbal mixture (Kangtaile, which contained Paeonia lactiflora, licorice, dandelion, and tea polyphenols) on the growth performances, immune response, antioxidant capacity, and intestinal microbiota of weaned pigs. A total of 400 weaned pigs [Duroc × (Landrace × Yorkshire)] were randomly allocated into one of four treatments: the CON group, fed with basic diet; the HM1 group, fed with basal diet supplemented with 0.5 g herbal mixture/kg diet; the HM2 group, fed with basal diet supplemented with 1.0 g herbal mixture/kg diet; or the HM3 group, fed with basal diet supplemented with 1.5 g herbal mixture/kg diet. The results revealed that dietary supplementation with the herbal mixture for 28 days improved average daily gain and feed conversion ratio, while decreased the diarrhea rate of weaned pigs. Moreover, dietary supple-mentation with the herbal mixture improved the antioxidant capacity through increasing the activity of catalase (CAT) and the total antioxidant capacity (T-AOC) level, while decreasing the concentration of malondialdehyde (MDA) in the serum. Pigs supplemented with herbal mixture presented an increased serum immunoglobulin (Ig)M level on day 14 compared with control pigs. The herbal mixture altered the composition of intestinal microbiota by influencing the relative abundances of Firmicutes and Bacteroidetes at the phylum level. The relative abundances of the Firmicutes and Bacteroidetes were significantly related to the body weight gain of pigs. In conclusion, supplementation of herbal mixture to the diet improved growth performance, immunity, and antioxidant capacity and modified the composition of intestinal microbiota in weaning pigs. This study provided new insights into the nutritional regulation effects of the herbal mixtures on weaned pigs.

Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression.

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.

Dietary pectin caused great changes in bile acid profiles of Pelteobagrus fulvidraco.

To reveal the impact of dietary fiber (DF) on the bile acid (BA) profiles of fish, yellow catfish (Pelteobagrus fulvidraco) were fed a diet containing 300 g kg-1 dextrin (CON diet, control) or pectin (a type of soluble DF, PEC diet) for 7 days, and then the BA profiles were analyzed by UHPLC-MS/MS. A total of 26 individuals of BAs were detected in the fish body, with 8, 10, 14, and 22 individuals of BAs detected in the liver, serum, bile, and hindgut digesta, respectively. The conjugated BAs (CBAs) of fish were dominated by taurine CBAs (TCBAs). The concentrations of free BAs (FBAs) and the value of FBAs/CBAs in the bile of fish fed the PEC diet were nearly 5 and 7 times higher, respectively than those in fish fed the CON diet. The value of glycine CBAs/TCBAs in the liver, serum and bile of fish fed the PEC diet was significantly lower, and in the hindgut digesta was higher than that of fish fed the CON diet (P < 0.05). These results suggested that dietary pectin greatly changed the BA profiles of Pelteobagrus fulvidraco, attributed to inhibition of reabsorption of BAs. Therefore, attention should be paid to the impact on BA homeostasis when replacing fishmeal with DF-rich plant ingredients in the fish diet.

The protective effects of yellow tea extract against loperamide-induced constipation in mice.

Yellow tea, a rare type tea from China, has a rich breadth of functional ingredients and benefits the gastrointestinal tract. However, it is not clear whether the yellow tea extract can alleviate constipation. Therefore, we used loperamide-induced constipation in mice to evaluate the effects of yellow tea extract. Fifty Kunming mice were randomly divided into five groups: normal, model, low-dose yellow tea extract, low-dose yellow tea extract prevention group, and high-dose yellow tea extract prevention group. Mice were administered yellow tea extract for 5 weeks followed by loperamide-induced constipation for the final 2 weeks. The results showed that yellow tea extract alleviated constipation symptoms by improving the fecal water content, defecation weight, and gastrointestinal transit rate. Yellow tea extract intervention also protected colon tissue, regulated serum neurotransmitters, and decreased the vasoactive intestinal peptide level. Furthermore, qRT-PCR indicated that yellow tea extract regulated genes associated with the constipation state, raised 5-HT3 and 5-HT4 and reduced AQP3 and AQP4 mRNA expression. Moreover, we found that yellow tea extract changed the gut microbiota composition. Community diversity and richness were increased and principal co-ordinate analysis demonstrated that the yellow tea extract prophylaxis groups differed from the model group. Difference analysis indicated that yellow tea extract increased Roseburia, Lachnospiraceae_UCG-006, and Bifidobacterium and decreased norank_f_Clostridiales_vadinBB60_group, unclassified_o_Bacteroidales, and Bacteroides, which are correlated with constipation. Based on these results, we believe that regular yellow tea consumption can effectively alleviate constipation.

Salidroside protects mice against CCl4-induced acute liver injury via down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation.

Salidroside (Sal), a natural phenolic compound isolated from Rhodiola sachalinensis, has been utilized as anti-inflammatory and antioxidant for centuries, however, its effects against liver injury and the underlying mechanisms are unclear. This study was designed to evaluate the protective effects and underlying mechanisms of Sal on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice. C57BL/6 mice were pretreated with Sal before CCl4 injection, the serum and liver tissue were collected to evaluate liver damage and molecular indices. The results showed that Sal pretreatment dose-dependently attenuated CCl4-induced acute liver injury, as indicated by lowering the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inhibiting hepatic pathological damage and apoptosis. In addition, Sal alleviated CCl4-primed oxidative stress and inflammatory response by restoring hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and inhibiting cytokines. Finally, Sal also down-regulated the expression of cytochrome P4502E1 (CYP2E1), and Nod-like receptor protein 3 (NLRP3) inflammasome activation in the liver of mice by CCl4. Our study demonstrates that Sal exerts its hepatoprotective effects on ALI through its antioxidant and anti-inflammatory effects, which might be mediated by down-regulating CYP2E1 expression and inhibiting NLRP3 inflammasome activation.

Ginsenoside Rg1 protects against d-galactose induced fatty liver disease in a mouse model via FOXO1 transcriptional factor.

AIMS: Rg1 is the most active component of traditional Chinese medicine ginseng, having anti-aging and anti-oxidative stress features in multiple organs. Cellular senescence of hepatocytes is involved in the progression of a wide spectrum of chronic liver diseases. In this study, we investigated the potential benefits and mechanism of action of Rg1 on aging-driven chronic liver diseases. MATERIALS AND METHODS: A total of 40 male C57BL/6 mice were randomly divided into four groups: control group; Rg1 group; Rg1+d-gal group; and d-gal group. Blood and liver tissue samples were collected for determination of liver function, biochemical and molecular markers, as well as histopathological investigation. KEY FINDINGS: Rg1 played an anti-aging role in reversing d-galactose induced increase in senescence-associated SA-ß-gal staining and p53, p21 protein in hepatocytes of mice and sustained mitochondria homeostasis. Meanwhile, Rg1 protected livers from d-galactose caused abnormal elevation of ALT and AST in serum, hepatic steatosis, reduction in hepatic glucose production, hydrogenic degeneration, inflammatory phenomena including senescence-associated secretory phenotype (SASP) IL-1ß, IL-6, MCP-1 elevation and lymphocyte infiltration. Furthermore, Rg1 suppressed drastic elevation in FOXO1 phosphorylation resulting in maintaining FOXO1 protein level in the liver after d-galactose treatment, followed by FOXO1 targeted antioxidase SOD and CAT significant up-regulation concurrent with marked decrease in lipid peroxidation marker MDA. SIGNIFICANCE: Rg1 exerts pharmaceutic effects of maintaining FOXO1 activity in liver, which enhances anti-oxidation potential of Rg1 to ameliorate SASP and to inhibit inflammation, also promotes metabolic homeostasis, and thus protects livers from senescence induced fatty liver disease. The study provides a potential therapeutic strategy for alleviating chronic liver pathology.

[Effect of electroacupuncture on the expression of insulin signal pathway related proteins in hippocampus in mice with Alzheimer's disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD. METHODS: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pS21GSK3α, and the number of hippocampal senile plaques (SP) was observed. RESULTS: The proteins of P85α, P110α, GSK3α and pS21GSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α was significantly decreased (P<0.01, P<0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased (P<0.001), and the distribution level of pS21GSK3α, P85α and P110α in hippocampus was significantly increased (P<0.05, P<0.001). The Western blot results showed compared with the control group, the expression of pS21GSK3α, P85α and P110α as well as the ratio of pS21GSK3α/GSK3α in the hippocampus in the model group were significantly decreased (P<0.001), and the expression of GSK3α was increased (P<0.05); compared with the model group, the expression of pS21GSK3α, P85α, P110α and the ratio of pS21GSK3α/GSK3α in the hippocampus in the treatment group were significantly increased (P<0.01, P<0.001), and the expression of GSK3α was decreased (P<0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased (P<0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased (P<0.01). CONCLUSION: EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.

Acute vasoreactivity testing predicts outcome of idiopathic pulmonary arterial hypertension patients with a negative acute response.

BACKGROUND: Acute vasoreactivity testing (AVT) during right heart catheterization (RHC) is performed in certain subsets of patients with pulmonary arterial hypertension (PAH) in order to identify those who benefit from calcium channel blockers. The present study aimed to investigate the prognostic value of pre-AVT, post-AVT, and changes in AVT (ΔAVT) parameters for idiopathic PAH (IPAH) patients with a negative acute response, and to identify sex differences that could be of prognostic value. METHODS: A total of 487 incident IPAH patients (171 males and 316 females) with a negative acute response to AVT were recruited from Shanghai Pulmonary Hospital between 2009 and 2018. Outcomes were predicted using the Kaplan-Meier curve and univariate/multivariate Cox regression analyses. All patients were followed up till January 2020, with outcome specified as all-cause mortality. RESULTS: Inhalation of iloprost aerosol improved the hemodynamic parameters for all patients. Post-PVR was decreased, and post-cardiac output (post-CO) and post-cardiac index (post-CI) were increased compared with pre-AVT parameters among males. Increased post- artery oxygen saturation (post-SaO2) and decreased post-mean right atrium pressure (post-mRAP) were also observed in females. For all patients, pre-CO ≥3.25 L/min, post-mPAP <53 mmHg, and post-mixed venous oxygen saturation (post-SvO2) ≤63% were parameters suggesting better prognosis. For males, patients with pre-PVR <12.47 Wood units, pre-SvO2 ≥64%, and post-mean pulmonary artery pressure (post-mPAP) <51 mmHg had a better prognosis. For females, patients with ΔmPAP ≥-4 mmHg and ΔPVR ≥-0.25 Wood units had better outcomes. CONCLUSIONS: AVT parameters, including pre-AVT, post-AVT and ΔAVT, have a more important prognostic value than currently used for identify a small subgroup of patients with PAH who are suitable for high-dose calcium channel blockers. Sex differences in AVT parameters suggest that sex should be taken into account in estimating prognosis.

Glycyrrhetinic acid pretreatment attenuates liver ischemia/reperfusion injury via inhibiting TLR4 signaling cascade in mice.

Glycyrrhetinic acid (GA), the main bioactive substances of glycyrrhiza uralensis Fisch, has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the effects and underlying mechanisms of GA in liver ischemia/reperfusion (I/R) injury remain elusive. In this study, mice were pretreated with GA (100 mg/kg) three times a day by gavage prior to I/R injury, and then hepatic histopathological damages, biochemical parameters and inflammatory molecules were evaluated. We found that mice performed with liver I/R showed a significantly increase in plasma aminotransferase (ALT), aspartate aminotransferase (AST), liver cell apoptosis and infiltration of neutrophils compared with the control group. GA pretreatment notably improved liver function, histopathology of liver tissues, and lowered liver cell apoptosis and infiltration of neutrophils. Besides, further analysis indicated that GA pretreatment reduced I/R-induced expression of extracellular HMGB1, inhibited activation of TLR4 and following phosphorylation of IRAK1, ERK, P38 and NF-κB, and attenuated TNF-α and IL-1ß production. These data suggested that GA protected against liver I/R injury through a HMGB1-TLR4 signaling pathway and it might be a promising drug for future clinical use in liver transplantation.

Ecological risk of combined pollution on soil ecosystem functions: Insight from the functional sensitivity and stability.

Assessing the ecological risk of combined pollution, especially from a holistic perspective with the consideration of the overarching functions of soil ecosystem, is crucial and beneficial to the improvement of ecological risk assessment (ERA) framework. In this study, four soils with similar physicochemical properties but contrasting heavy metals contamination levels were selected to explore changes in the integrated functional sensitivity (MSI), resistance (MRS) and resilience (MRL) of soil microbial communities subjected to herbicide siduron, based on which the ecological risk of the accumulation of siduron in the four studied soils were evaluated. The results suggested that the microbial biomass carbon, activity of denitrification enzyme and nitrogenase were indicative of MSI and MRS, and the same three parameters plus soil basal respiration were indicative of MRL. Significant dose-effect relationships between siduron residues in soils and MSI, MRS and MRL under combined pollution were observed. Heavy metal polluted soils showed higher sensitivity and lower resistance to the additional disturbance of herbicide siduron due to the lower microbial biomass, while the resilience of heavy metal polluted soils was much higher due to the pre-adaption to the chemical stresses. The quantifiable indicator microbial functional stability was incorporated in the framework of ERA and the results showed that the accumulation of siduron in the studied soils could exhibit potential harm to the integrated functional stability of soil microbial community. Thus, this work provides insights into the application of integrated function of soil microbial community into the framework of ERA.

Radioprotective effect of epimedium on neurogenesis and cognition after acute radiation exposure.

The radioprotective effect of herb epimedium (or yin yang huo) extract (5 g/kg, oral administration daily for 4 weeks) on neurogenesis and cognition after acute radiation exposure with 5.5 Gy was evaluated in Balb/c mice by behavioral tests and immunohistochemical study. The results indicated that epimedium extract could improve animal weight loss, locomotor activity and spatial learning and memory which are similar to pre-irradiation intraperitoneal injection (100 mg/kg) of amifostine phosphate, a well- known radioprotective drug. Immunohistochemical study showed that epimedium extract prevented the loss of proliferation cells, newly generated neurons, and interneurons in the hilus, in particular, the subgranular zone of the dentate gyrus. It suggests that herb epimedium may be a promising radio-neuro-protective drug to prevent radiation-induced neuropsychological disorders.

Hyaluronic Acid-Functionalized Gadolinium Doped Iron Oxide Nanoparticles for Atherosclerosis-Targeted Mr Imaging.

Magnetic resonance imaging (MRI) contrast agents (CTs) with both positive (T1) and negative (T2) contrast abilities have attracted considerable interests due to their complementary diagnostic information for more precise diagnosis. In this study, gadolinium-doped oxide nanoparticles functionalized by hyaluronic acid (HA-GdIO NPs) were synthesized for atherosclerosis-targeting T1-T2 dual-model MR imaging. The results showed that the HA-GdIO NPs exhibited high magnetic susceptibility and good biocompatibility. After being coated with HA, the HA-GdIO NPs specifically accumulated in the atherosclerosis plaques through targeting CD44-overpression macrophages which played a central role in development of atherosclerotic plaques. Furthermore, the HA-GdIO NPs can provide enhanced T1 and T2 dual phase contrast effects in vitro and in vivo, particularly in the vascular regions of mice. This work may provide a promising idea to construct MRI contrast agents with both effective and targeted contrast abilities for biomedical applications.

Paeoniflorin protects against liver ischemia/reperfusion injury in mice via inhibiting HMGB1-TLR4 signaling pathway.

Hepatic ischemia/reperfusion (I/R) injury is a major cause of high morbidity and mortality after liver resection, transplantation, and hemorrhagic shock. Paeoniflorin (PF), the main substance of glucosides in Radix Paeoniae Alba, has been widely used to treat various hepatic inflammatory diseases including I/R injury. However, the underlying mechanisms of PF on hepatic I/R injury remain further investigated. In this study, the liver I/R model was performed by clamping the portal vein and hepatic artery with an atraumatic clamp for 90 min followed by 6 hr reperfusion. PF (100 mg/kg) was given three times a day by gavage before I/R. The blood and hepatic samples were collected to evaluate liver injury and molecular indexes. The results showed that PF pretreatment significantly inhibited I/R-induced serum ALT and AST activities (40.3% and 53.8% those of I/R group, respectively), hepatic pathological damages and hepatic apoptosis (P < 0.01), and infiltration of neutrophils into liver. In addition, PF suppressed the production of pro-inflammatory cytokines (P < 0.01), decreased the expression of high mobility group box-1 (HMGB1), and down-regulated toll-like receptors 4 (TLR4) and phosphorylated ERK1/2, JNK1/2, p38, and NF-κB signal molecules expression in the I/R-operated mice. These findings indicated that PF played a protective role in liver I/R injury, and this protection was associated with inhibition of I/R-activated HMGB1-TLR4 signaling pathway to attenuate hepatic inflammation responses.