Quercetin influences intestinal dysbacteriosis and delays alveolar epithelial cell senescence by regulating PTEN/PI3K/AKT signaling in pulmonary fibrosis.

Pulmonary fibrosis is a chronic and progressive lung disease with high mortality. This study aims to explore the protective mechanism of quercetin against pulmonary fibrosis regarding cell senescence and gut microbiota. Rats were intratracheally injected with bleomycin (BLM) to establish a pulmonary fibrosis rat model. RLE-6TN cells were stimulated with BLM to build the model of alveolar epithelial cell senescence, and RLE-6TN-derived conditional medium (CM) was harvested to further culture fibroblasts. Histopathological changes were assessed by H&E and Masson staining. α-SMA expression was assessed by immunofluorescence assay. Senescence-associated ß-galactosidase (SA-ß-gal) staining and senescence-associated secretory phenotype (SASP) cytokine assay were conducted to assess cellular senescence. Gut microbiota was analyzed by 16S rRNA gene sequencing. The fibrosis-, senescence-, and PTEN/PI3K/AKT signaling-related proteins were examined by western blot. In BLM-induced pulmonary fibrosis rats, quercetin exerted its protective effects by reducing histological injury and collagen deposition, lessening cellular senescence, and regulating gut microbiota. In BLM-induced alveolar epithelial cell senescence, quercetin inhibited senescence, lessened SASP cytokine secretion of alveolar epithelial cells, and further ameliorated collagen deposition in fibroblasts. In addition, quercetin might exert its functional effects by regulating the PTEN/PI3K/AKT signaling pathway. Moreover, quercetin regulated intestinal dysbacteriosis in BLM-induced pulmonary fibrosis rats, especially boosting the abundance of Akkermansia. To conclude, our findings provide an in-depth understanding of the potential mechanism behind the protective role of quercetin against pulmonary fibrosis.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study.

Objectives: Aficamten is a selective, small-molecule allosteric inhibitor of cardiac sarcomere being developed as a chronic oral treatment for patients with symptomatic obstructive hypertrophic cardiomyopathy. This was the first-in-Chinese study aiming to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of aficamten in healthy adults. Methods: This double-blind, randomized, placebo-controlled, phase 1 study was conducted in 28 healthy male and female Chinese participants after single ascending dose (SAD) and multi-dose (MD) administrations of aficamten. In the SAD cohort, 16 participants were randomized to receive a single oral dose of aficamten: 10 mg, 20 mg, or placebo. In the MD cohort, 12 participants were randomized to receive multiple doses of aficamten: 5 mg or placebo once daily for 14 days. Safety was monitored throughout the study with electrocardiograms, echocardiograms, clinical laboratory tests, and reporting of adverse events (AEs). Pharmacokinetic profiles of aficamten and metabolites, as well as CYP2D6 genetic impact, were evaluated. Results: A total of 35 treatment-emergent AEs were reported by 14 (50%) participants with mild severity. There were no serious AEs or adverse decreases in left ventricular ejection fraction below 50% during the study. Aficamten was dose-proportional over the dose range of 5-20 mg and accumulated in the MD cohort. Conclusion: Aficamten was safe and well-tolerated in the healthy Chinese adult participants. The pharmacokinetics of aficamten in the Chinese population was comparable to those previously found in Western participants. These phase 1 data support the progression of aficamten into future clinical studies in Chinese patients. Clinical Trial registration: https://clinicaltrials.gov, identifier: NCT04783766.

Proteomic and Phenotypic Studies of Mycoplasma pneumoniae Revealed Macrolide-Resistant Mutation (A2063G) Associated Changes in Protein Composition and Pathogenicity of Type I Strains.

Mycoplasma pneumoniae (MP) is an important respiratory pathogen, the prevalence of macrolide-resistant MP (mainly containing A2063G mutation in 23S rRNA) increased in recent years. Epidemiological studies suggest a higher prevalence of type I resistant (IR) strains than corresponding sensitive (IS/IIS) strains, but not type II resistant (IIR) strains. Here, we aimed to analyze the factors underlying the altered prevalence of IR strains. First, proteomic analyses exhibit the protein compositions were type specific, while more differential proteins were detected between IS and IR (227) than IIS and IIR strains (81). mRNA level detection suggested posttranscriptional regulation of these differential proteins. Differential protein-related phenotypic changes were also detected: (i) P1 abundance was different between genotypes (I < II, IR < IS), the adhesion of MPs showed accordance to P1 abundance within IS and IIS strains; (ii) type I, especially IR, strains had a higher proliferation rate, which is potentially associated with differential proteins participating in glycolysis and one carbon pool metabolisms; (iii) A549 cells infected with IR strains had lower activity of caspase-3 and higher levels IL-8, but the differences were not significant between groups (P > 0.05). Correlations of P1 abundance to caspase-3 activity and proliferation rate to the level of IL-8 were obtained. These results suggest changes in protein composition influenced the pathogenicity of MP, especially in IR strains, which may impact the prevalence of MP strains of different genotypes. IMPORTANCE The prevalence of macrolide-resistant MPs increased the difficulty in treatment of MP infections and posed potential threats to children's health. Epidemiological studies showed a high prevalence of IR-resistant strains (mainly A2063G in 23S rRNA) in these years. However, the trigger mechanisms for this phenomenon are not clear. In this paper, proteomic and phenotypic studies suggest that IR strains have reduced levels of multiple adhesion proteins and increased proliferation rate, which may lead to higher transmission rate of IR strains in the population. This suggests that we should pay attention to the prevalence of IR strains.

Genetic association of telomere length, obesity and tobacoo smoking with idiopathic pulmonary fibrosis risk.

BACKGROUND: Due to the inadequacy of published evidence, association of telomere length (TL), obesity and tobacco smoking with idiopathic pulmonary fibrosis (IPF) remains unclear. The aim of the study was to explore whether these exposures genetically affected the risk of the disease. METHODS: Genetic variants from genome-wide association studies for TL, body mass index (BMI), body fat percentage (BFP) and tobacco smoking (including maternal smoking) were used as instrumental variables. Inverse-variance weighted were mainly adopted to determine the genetic association of these exposures with IPF. All analyses were conducted by R-software (version 3.6.1). RESULTS: Firstly, longer TL was associated with the decreased risk of IPF (OR = 0.475 per SD increase in TL, 95%CI = 0.336 ~ 0.670, P<0.001). Secondly, higher levels of BMI and BFP were related to the increased risk of the disease (OR = 1.425 per SD increase in BMI level, 95%CI = 1.114 ~ 1.823, P = 0.005; OR = 1.702 per SD increase in BFP level, 95%CI = 1.202 ~ 2.409, P = 0.003). Thirdly, maternal smoking was implicated in the increased risk of the disease (OR = 13.183 per SD increase in the prevalence of maternal smoking, 95%CI = 1.820 ~ 95.484, P = 0.011). CONCLUSION: TL should be a genetic risk factor for IPF. Obesity and exposure to tobacco smoking as a fetus might also contribute to the development of this fibrotic diseases. These findings should be verified by future studies.

Cell damage and neutrophils promote the infection of Mycoplasma pneumoniae and inflammatory response.

Mycoplasma pneumoniae (MP) is an important respiratory pathogen of human. The infection of MP can cause direct damage and immune damage in lung, resulting in Mycoplasma pneumoniae pneumonia (MPP). In this study, we aim to investigate the pathogenesis of MPP by detecting the proliferation of MP under conditions of cell damages and neutrophils in vitro. Firstly, we found the supplements of intracellular fluid, protein and RNA derived from intracellular fluid of A549 cells contribute to the survival of MP, thereby promoting the infection of MP. Cell damage can also significantly contribute to the survival of MP without supplements. At the same time, the additions of supplements contribute to apoptosis and the expression of IL-8 and IL-1ß. Further, we found live neutrophils show bactericidal activity to MP, and the phagocytosis of MP promotes apoptosis of neutrophils. When co-incubated with MP and A549 cells, the proliferation of MP in the high neutrophils proportion groups were accelerated with functional decline of neutrophils, and the level of extracellular IL-1ß showed a time and dose dependent manner to neutrophils. These results suggest that the release of intracellular nutrients by damaged cells and functional decline of neutrophils can promote the infection of MP and play roles in the activation of inflammatory response. Therefore, lung damage and infiltration of neutrophils would be important factors affecting the development of MPP.

Therapeutic targeting of the mevalonate-geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell lung cancer.

Small cell lung cancer (SCLC) lacks effective treatments to overcome chemoresistance. Here we established multiple human chemoresistant xenograft models through long-term intermittent chemotherapy, mimicking clinically relevant therapeutic settings. We show that chemoresistant SCLC undergoes metabolic reprogramming relying on the mevalonate (MVA)-geranylgeranyl diphosphate (GGPP) pathway, which can be targeted using clinically approved statins. Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase 1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC. Finally, we demonstrate that combined statin and chemotherapy treatment resulted in durable responses in three patients with SCLC who relapsed from first-line chemotherapy. Collectively, these data uncover the MVA-GGPP pathway as a metabolic vulnerability in SCLC and identify statins as a potentially effective treatment to overcome chemoresistance.

Mechanism of Infantile Feire Kechuan Oral Solution against Mycoplasma pneumoniae infection of A549 cells.

BACKGROUND: Mycoplasma pneumoniae is a leading cause of community-acquired respiratory infections. Infantile Feire Kechuan Oral Solution (IFKOS) is effective for treatment of M. pneumoniae infection. The aim of this study was to explore the potential mechanism of IFKOS against M. pneumoniae infection in basal epithelial human lung adenocarcinoma A549 cells. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the effects of IFKOS on the viability of A549 cells infected with M. pneumoniae. Optical microscopy was used to observe cell morphology and a Muse cell analyzer was used to assess apoptosis and the cell cycle phase. Enzyme-linked immunosorbent assays were employed to assess the expression levels of interleukin (IL)-4, IL-6, IL-8, IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-α, and IFN-γ. RESULTS: Under certain conditions, M. pneumoniae infection reduced the viability and inhibited the proliferation of A549 cells, promoted early apoptosis, and arrested cells in the G0/G1 phase, thus shortening the S and G2/M phases (all p < 0.05). M. pneumoniae also upregulated expression of IL-8 and TNF-α and downregulated that of IL-6 (p < 0.05), which switched the immune balance of Th1/Th2 to Th1 cells. IFKOS (5.531 mg/mL) improved the viability and proliferation of M. pneumoniae-infected A549 cells, mitigated early apoptosis, and reversed cell cycle arrest in the G0/G1 phase, thereby extending the S and G2/M phases (all, p < 0.05). IFKOS downregulated expression of IL-8 and TNF-α and upregulated that of IL-6 (p < 0.01), thereby reversing the immune imbalance of Th1/Th2. Secretion of IL-4, IL-17, IFN-α, and IFN-γ was not observed. CONCLUSION: IFKOS played a protective role in the regulation of cell viability, apoptosis, the cell cycle, and Th1/Th2 immune imbalance induced by M. pneumoniae infection and conveyed an anti-inflammatory effect in A549 cells.

Serum cytokine profiling reveals different immune response patterns during general and severe Mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae (MP) is an important human pathogen that mainly affects children causing general and severe Mycoplasma pneumoniae pneumonia (G/SMPP). In the present study, a comprehensive immune response data (33 cytokines) was obtained in school-age children (3-9 years old) during MPP, aiming to analyze the immune response patterns during MPP. At acute phase, changes of cytokines were both detected in GMPP (24/33) and SMPP (23/33) groups compared to the healthy group (p < 0.05), with 20 identical cytokines. Between MPP groups, the levels of 13 cytokines (IL-2, IL-10, IL-11, IL-12, IL-20, IL-28A, IL-32, IL-35, IFN-α2, IFN-γ, IFN-ß, BAFF, and TSLP) were higher and three cytokines (LIGHT, OPN and CHI3L1) were lower in the SMPP group than in the GMPP group (p < 0.05). Function analysis reveals that macrophage function (sCD163, CHI3L1) are not activated in both MPP groups; difference in regulatory patterns of T cells (IL26, IL27, OPN, LIGHT) and defective activation of B cells (BAFF) were detected in the SMPP group compared to the GMPP group. Besides, the level of osteocalcin; sIL-6Rß and MMP-2 are both decreased in MPP groups at acute and convalescent phases compared to the healthy group, among which the levels of sIL-6Rß and MMP-2 showed negative correlations (p < 0.1) to the application of bronchial lavage in SMPP group, indicating their roles in the development of MPP. At the convalescent phase, more cytokines recovered in GMPP (18) than SMPP (11), revealing better controlled immune response during GMPP. These results reveal different immune response patterns during GMPP and SMPP. In addition, the differentiated cytokines may serve as potential indicators of SMPP; early intervention on immune response regulations may be helpful in reducing the severity of SMPP.

Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold.

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

Analysis of the Point Prevalence and Influencing Factors of Acute Stress Disorder in Elderly Patients with Osteoporotic Fractures.

BACKGROUND: Increasing attention has been paid to posttraumatic affective disorders. However, orthopedic surgeons dealing with trauma often ignore the harm of such diseases. OBJECTIVE: To investigate the point prevalence and influencing factors of acute stress disorder (ASD) in elderly patients with osteoporotic fractures (EPOFs) from the perspective of orthopedic surgeons. PATIENTS AND METHODS: A total of 595 cases of EPOFs were treated at our hospital from January 1, 2018, to June 30, 2019. The patients meeting our inclusion criteria were assessed using a structured interview based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria to verify the presence of ASD. After diagnosis, the participants were divided into two groups (those with and without ASD). The sociodemographic characteristics, disease characteristics, and Social Support Rating Scale (SSRS) scores were assessed. The chi-square test was used for univariate analysis, and multivariate analysis was performed using binary logistic regression. RESULTS: Of the 524 participants, 32 (6.1%) met the criteria for the diagnosis of ASD. The results of the univariate analysis showed that gender, personality, living alone, monthly family income, initial fear, poor prognosis expectation, anxiety/depression, pain, and social support were associated with ASD in EPOFs (P<0.05). The multivariate regression analysis showed that isolation, low monthly family income, introversion, poor prognosis expectation, previous traumatic history, and intense pain were the main influencing factors and risk factors (OR>1) for ASD in EPOFs. CONCLUSION: Being female, living alone, introversion, poor family income, intense initial fear, poor prognosis expectation, anxiety/depression, intense pain perception and low social support were significantly related to the occurrence of ASD in EPOFs. To achieve optimal recovery in EPOFs, orthopedic surgeons should meet both the physiological and psychological needs of the patients.

Efficacy and safety of unilateral and bilateral percutaneous balloon kyphoplasty for AOspineA3/A4 osteoporotic thoracolumbar burst fractures.

To retrospectively evaluate the efficacy and safety of unilateral and bilateral percutaneous balloon kyphoplasty (PKP) in the treatment of osteoporotic thoracolumbar burst fractures.Retrospectively collected clinical data of 138 patients with osteoporotic thoracolumbar burst fractures who underwent unilateral (n = 70) and bilateral (n = 68) PKP in our hospital from March 2015 to December 2018. The general conditions, operation time, radiation exposure time, intraoperative blood loss, bone cement dosage, hospitalization expenses, and complications were collected from the two groups. Visual analog scale (VAS) values, Cobb's angle changes, average vertebral height changes, and Oswestry Dysfunction Index (ODI) values before treatment, 1 month, and 6 months after treatment were collected.There was no significant difference in gender (male: 28 vs 22; female 42 vs 46) and age (70.25 ±â€Š7.10 vs 69.82 ±â€Š8.20, P > .05) distribution between the two groups. The VAS score (7.38 ±â€Š1.34 vs 2.52 ±â€Š0.99, P < .05), ODI (77.24 ±â€Š6.98 vs 23.11 ±â€Š3.54, P < .05), vertebral mean height (16.71 ±â€Š2.18 vs 17.05 ±â€Š1.94, P < .05) and Cobb's angle (20.26 ±â€Š3.21 vs 11.58 ±â€Š3.20, P < .05) of the two groups were significantly improved after operation, but there was no significant difference between the two groups (P > .05). There was no significant difference in the rate of cement leakage (10.29% vs 11.42%, P > .05), incision swelling (30.88% vs 19.71%, P > .05) and incidence of adjacent vertebrae (4.41% vs 5.71%, P > .05) between the two groups. Compared with bilateral PKP group, operation time (50.88 ±â€Š7.38 vs 62.18 ±â€Š8.01), intraoperative blood loss (14.54 ±â€Š3.16 vs 22.03 ±â€Š5.92), radiation exposure time (23.74 ±â€Š3.41 vs 15.22 ±â€Š3.70), bone cement dosage (4.36 ±â€Š0.81 vs 5.16 ±â€Š0.77) and hospitalization costs (2.38 ±â€Š0.08 vs 2.74 ±â€Š0.07) were significantly lower in the unilateral PKP group (P < .05).Bilateral PKP and unilateral PKP have the same efficacy and safety in the treatment of osteoporotic thoracolumbar burst fractures. However, the unilateral PKP has the characteristics of short operation time, small trauma, low cost and short radiation exposure time, and has clinical application value.

Influence of Ketorolac Supplementation on Pain Control for Knee Arthroscopy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy of ketorolac supplementation on pain control for knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the impact of ketorolac supplementation on pain intensity after knee arthroscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2018 for randomized controlled trials (RCTs) assessing the effect of ketorolac supplementation vs placebo on pain management after knee arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS: Ten RCTs involving 402 patients are included in the meta-analysis. Overall, compared with control group for knee arthroscopy, ketorolac supplementation is associated with notably reduced pain scores at 1 h (MD = -0.66; 95% CI = -1.12 to -0.21; P = 0.004) and 2 h (MD = -0.90; 95% CI = -1.74 to -0.07; P = 0.03), prolonged time for first analgesic requirement (MD = 1.94; 95% CI = 0.33 to 3.55; P = 0.02) and decreased number of analgesic requirement (RR = 0.41; 95% CI = 0.23 to 0.75; P = 0.003), but has no obvious impact on analgesic consumption (MD = -0.56; 95% CI = -1.14 to 0.02; P = 0.06), as well as nausea and vomiting (RR = 0.44; 95% CI = 0.12 to 0.21; P = 0.21). CONCLUSIONS: Ketorolac supplementation is effective to produce pain relief for knee arthroscopy.

The efficacy of celecoxib for pain management of arthroscopy: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of celecoxib for pain management of arthroscopy remains controversial. We conduct a systematic review and meta-analysis to assess if celecoxib before the surgery decreases postoperative pain intensity of arthroscopy. METHODS: We search PubMed, Embase, Web of science, EBSCO, and Cochrane library databases for randomized controlled trials (RCTs) assessing the effect of celecoxib versus placebo on pain control of arthroscopy. RESULTS: Five RCTs are included in the meta-analysis. Celecoxib is administered at 200 mg or 400 mg dosage before the surgery. Overall, compared with control group for arthroscopy, preemptive celecoxib has remarkably positive impact on pain scores at 2 to 6 hours (standard mean difference (SMD) = -0.66; 95% confidence interval (CI) = -0.95 to -0.36; P < .0001) and 24 hours after the surgery (SMD = -1.26; 95% CI = -1.83 to -0.70; P < 0.0001), analgesic consumption (SMD  = -2.73; 95% CI = -5.17 to -0.28; P = .03), as well as the decrease in adverse events (risk ratio (RR) = 0.56; 95% CI = 0.39 to 0.79; P = .001), but shows no obvious effect on first time for analgesic requirement (SMD  = 0.02; 95% CI = -0.22 to 0.26; P = .87), nausea, or vomiting (RR = 0.70; 95% CI = 0.42 to 1.17; P = .18). CONCLUSION: Celecoxib administered at 200 mg or 400 mg dosage before the surgery decreases postoperative pain intensity of arthroscopy.

Evaluation of the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid composite screws for intraarticular fractures in rabbits.

OBJECTIVE: To evaluate the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) composite screws in the intraarticular fracture model. MATERIALS AND METHODS: A total of 35 New Zealand White rabbits were used in a bilateral femoral intercondylar fracture model and randomly divided into two groups. n-CDHA/PAA screws were used in the experimental group, and medical metal screws were used in the control group. The fracture condition, range of motion, and the screw push-out strength were assessed, and an arthroscopic examination of knee joint was performed at 4, 8, and 12 weeks after surgery. The biodegradation of the n-CDHA/PAA screws in vivo was tested through weighing, and changes in screw structure were assessed by X-ray diffraction at 12 weeks after surgery. RESULTS: The general situation of all animals was good and showed no incision infection and dehiscence after surgery. X-ray scanning showed that significant callus growth was present in both groups at 4 weeks after surgery, and there was no significant difference (P>0.05) in the Lane-Sandhu score between the experimental and control groups at all time points after surgery. There were no statistically significant differences (P>0.05) in the range of motion and Oswestry Arthroscopy Score of arthroscopic examination of the knee joints between the two groups. The screw push-out strength of the control group was stronger than that of the experimental group at 4 weeks after surgery (P<0.05), but after that, there was no significant difference between the groups (P>0.05). The degradation tests showed that the n-CDHA/PAA screws degraded gradually after implantation, and the weight loss rate was approximately 16% at 12 weeks after surgery. The X-ray diffraction results showed that the crystal structure of the outer surface of the n-CDHA/PAA screw has changed at 12 weeks after surgery. CONCLUSION: The n-CDHA/PAA screw is an effective and safe implant as a potential internal fixation device for an intercondylar fracture of the femur, and its internal fixation effect was similar to that of medical metal screw.

Combined treatment with sinomenine and acupuncture on collagen-induced arthritis through the NF-κB and MAPK signaling pathway.

Sinomenine is a monomer extracted from the traditional Chinese medicine plant Sabia japonica, which possesses several pharmacological properties including prominent abirritation, mitigation, anti-inflammation, immune suppression, cough relief, stimulation of histamine release, decrease in blood pressure and antiarrhythmia. Sinomenine is clinically employed to treat rheumatic disease. To investigate the impact of combined sinomenine treatment with acupuncture on the progression of arthritis and explore the potential underlying molecular mechanisms, the present study analyzed a collagen-induced arthritis model. Results from the combined curative (CC) treatment group (combined treatment with sinomenine and acupuncture) demonstrated a decrease in volume changes and arthritis score changes within rat paws, and increased the overall body weight in arthritic rats. CC treatment significantly decreased tumor necrosis factor α, interleukin (IL)-6, IL-1ß and IL-8 serum levels in arthritic rats. CC treatment significantly increased superoxide dismutase and inhibited malondialdehyde levels in arthritic rats. The protein expression of cyclooxygenase-2, inducible nitric oxide synthase, matrix metalloproteinase (MMP)2 and MMP9 in arthritic rats was suppressed owing to CC treatment. Finally, nuclear factor κB and phosphorylated p38 mitogen-activated protein kinase (MAPK) protein expression in arthritic rats were also suppressed following CC treatment. The results indicate that the combined treatment of sinomenine and acupuncture on collagen-induced arthritis takes effect through the nuclear factor κB and MAPK signaling pathway.

Noninvasive predictive models of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: The aim of the present study was to establish noninvasive diagnostic models for liver fibrosis and assess their predictive accuracy (AC). METHODS: A total of 349 patients with chronic hepatitis B virus infection were evaluated, who underwent liver biopsy and pathologic examination at Beijing Ditan Hospital affiliated to Capital Medical University. Patients were subdivided in disease-immune tolerant (n = 125) and immune reactive HBeAg positive (n = 224) groups. Diagnostic models were based on independent markers of liver fibrosis. Receiver operating characteristic (ROC) curves were used to set cutoff values and determine the diagnostic value of the models. RESULTS: Wang I and Wang II models were constructed using independent disease markers. Wang I model cutoff values ≤ 1.75 and > 5.84 were used to identify patients in the immune tolerant phase with or without significant fibrosis. The area under the ROC curve (AUC) for this model was 0.866 (95% CI, 0.790, 0.942) and an AC of 92.0% was obtained. Wang II model cutoff values ≤ 3.79 and > 7.06 were used to identify immune reactive HBeAg-positive patients with or without significant fibrosis. AUC was 0.872 (95% CI, 0.824, 0.920), with an AC of 88.0%. CONCLUSIONS: Both Wang models enabled noninvasive liver fibrosis assessment with reliable predictive power and reproducibility for diagnosis of fibrosis in immune tolerant and immune reactive HBeAg-positive patients. With further development, these models may provide a clinical alternative to liver biopsy.

WITHDRAWN: Noninvasive predictive models of liver fibrosis in patients with chronic hepatitis B.

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