Evaluation of drug interactions of Saposhnikoviae Radix and its major components with astragaloside IV and paeoniflorin using in vitro and in vivo experiments.

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.

2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells.

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 µg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

Sublethal and Transgenerational Toxicities of Chlorfenapyr on Biological Traits and Enzyme Activities of Paracoccus marginatus (Hemiptera: Pseudococcidae).

Papaya mealybug, Paracoccus marginatus Williams and Granara de Willink (Hemiptera: Pseudococcidae), is an economically important, invasive insect that is now distributed worldwide. Chlorfenapyr has been demonstrated to have a significant control effect on P. marginatus. In order to evaluate the sublethal and transgenerational effects of chlorfenapyr on P. marginatus, the life table data of three consecutive generations were collected and analyzed by the age stage, two-sex life table method, and the enzyme activities were assayed using a spectrophotometer. The results showed that exposure to the insecticide had significant effects on the biological traits of subsequent generations of P. marginatus, and a higher intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and a shorter mean generation time (T) were observed in the chlorfenapyr-treated F1 mealybugs. Enzyme activity assays showed that chlorfenapyr significantly inhibited the activities of catalase (CAT) and peroxidase (POD) while activating the activities of superoxide dismutase (SOD), which suggested that SOD, CAT, and POD may play an important role in the self-defense of P. marginatus against chlorfenapyr. These results conclusively demonstrated that exposure of P. marginatus to sublethal concentrations of chlorfenapyr induced hormetic effects on the F1 generation while having negative effects on the F0 and F3 generations.

Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection.

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

The Novel Regulatory Role of the lncRNA-miRNA-mRNA Axis in Chronic Inflammatory Airway Diseases.

Chronic inflammatory airway diseases, characterized by airway inflammation and airway remodelling, are increasing as a cause of morbidity and mortality for all age groups and races across the world. The underlying molecular mechanisms involved in chronic inflammatory airway diseases have not been fully explored. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have recently attracted much attention for their roles in the regulation of a variety of biological processes. A number of studies have confirmed that both lncRNAs and miRNAs can regulate the initiation and progression of chronic airway diseases by targeting mRNAs and regulating different cellular processes, such as proliferation, apoptosis, inflammation, migration, and epithelial-mesenchymal transition (EMT). Recently, accumulative evidence has shown that the novel regulatory mechanism underlying the interaction among lncRNAs, miRNAs and messenger RNAs (mRNAs) plays a critical role in the pathophysiological processes of chronic inflammatory airway diseases. In this review, we comprehensively summarized the regulatory roles of the lncRNA-miRNA-mRNA network in different cell types and their potential roles as biomarkers, indicators of comorbidities or therapeutic targets for chronic inflammatory airway diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma.

CT Attenuation and Cross-Sectional Area of the Pectoralis Are Associated With Clinical Characteristics in Chronic Obstructive Pulmonary Disease Patients.

Purpose: Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). Computed tomography (CT) could serve as a method for muscle assessment due to its ability to measure both muscle quantity (e.g., cross-sectional muscle area) and muscle quality (e.g., muscle attenuation). Our study aimed to compare the differences in CT-derived pectoralis muscle cross-sectional area (PMA) and pectoralis muscle attenuation (PMT) between COPD patients and healthy controls and explore the association between PMA and PMT measurements and clinical characteristics in patients with COPD. Methods: A total of 252 participants included in our analysis consisted of 80 healthy controls and 172 patients with COPD. PMA and PMT were measured from a single axial slice of the CT scan above the aortic arch. Linear regression analysis was used to determine the correlation between PMA and PMT measurements and clinical characteristics in patients with COPD. Associations were adjusted for age, sex, BMI, FEV1%pred, smoking pack-years, current smoking status, emphysema percentage, and total airway count (TAC) of the right upper lobe apical bronchus (RB1). Results: PMA and PMT were lower in COPD patients, especially those with acute exacerbation, than in healthy controls. PMA and PMT were significantly associated with the severity of emphysema and the TAC of RB1 (p < 0.05). Patients with stable COPD, who had lower PMA and lower PMT, had significantly worse pulmonary function, poorer exercise tolerance, decreased quality of life, and worse dyspnea scores. In addition, patients with acute COPD exacerbation, who had lower PMA and lower PMT, had a higher risk of respiratory failure on admission. Conclusion: CT-derived measurements of the pectoralis muscle may be helpful in detecting declines in muscle quantity and quality and predicting disease severity in patients with COPD.

Surface charge switchable nano-micelle for pH/redox-triggered and endosomal escape mediated co-delivery of doxorubicin and paclitaxel in treatment of lung adenocarcinoma.

Recently, the stimulus-sensitive drug co-delivery system has gained increasing attentions in the clinic and exhibits improved efficiency rather than the mono-chemotherapy in anti-tumor therapy. Herein, the smart charge switchable nano-micelles (NMs) were fabricated for the endosomal escape mediated co-delivery of doxorubicin (DOX) and paclitaxel (PTX) in treatment of lung adenocarcinoma. The disulfide bonds were facilitated as the linker of the polymer backbone to achieve the redox-sensitive degradation by high intracellular GSH, and acid-liable DMMA was grafted onto DOX molecules for pH-triggered drug release under acidic tumoral microenvironment. Folic acid (FA) was utilized as targeting molecule for facilitating entry of the as prepared NMs into cancer cells. Remarkably, the as fabricated NMs exhibited surface charge-switch from negative to positive during transmitting from physiological pH to the tumor extracellular pH, which can improve the cellular internalization towards cancer cell. Subsequently, the "proton-sponge" effect mediated endosome escape of the NMs was facilitated in the acidic endo/lysosome environment. By the cell assay, the NMs possessed good biocompatibility, excellent cellular uptake, and improved inhibition rate against cancer cell. Moreover, the co-delivery of DOX/PTX exhibited synergistic and enhanced solid tumor inhibition efficiency comparing to mono-chemotherapy in A-549 tumor bearing mice model. Based on above experimental results, the as prepared drug co-delivery system showed promising biosafety and potentials for efficient lung adenocarcinoma treatment in clinic.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction.

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1ß, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

Lamiophlomis herba: A comprehensive overview of its chemical constituents, pharmacology, clinical applications, and quality control.

Lamiophlomis rotata (Benth.) Kudo (LR) is an extensively used Chinese herbal medicine. It contains a variety of chemical constituents with significant biological activities that were first recorded in the classical masterpiece of Tibetan Medicine, Somaratsa. In this review, we summarize the information regarding the traditional uses, chemical constituents, pharmacological effects, clinical applications, quality control, toxicology, and pharmacokinetics of LR. At least 223 chemical constituents have been isolated from LR, including phenylethanoid glycosides, flavonoids, iridoids, volatile oils, et al. Their various physiological activities have been demonstrated as analgesic, hemostatic, anti-inflammatory, anti-tumor, marrow-supplementing, anti-bacterial, and immunity-strengthening. The clinical applications of LR and quality control are also discussed, as well as some existing problems. This article aims to provide more comprehensive information on the chemical composition, pharmacological activity, and clinical application of LR, so as to provide a theoretical basis for the further reasonable development of LR in clinical practice and of new drugs.

Effectiveness of Telemonitoring for Reducing Exacerbation Occurrence in COPD Patients With Past Exacerbation History: A Systematic Review and Meta-Analysis.

Background: Although an increasing number of studies have reported that telemonitoring (TM) in patients with chronic obstructive pulmonary disease (COPD) can be useful and efficacious for hospitalizations and quality of life, its actual utility in detecting and managing acute exacerbation of COPD (AECOPD) is less established. This meta-analysis aimed to identify the best available evidence on the effectiveness of TM targeting the early and optimized management of AECOPD in patients with a history of past AECOPD compared with a control group without TM intervention. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from 1990 to May 2020. Primary endpoints included emergency room visits and exacerbation-related readmissions. P-values, risk ratios, odds ratios, and mean differences with 95% confidence intervals were calculated. Results: Of 505 identified citations, 17 original articles with both TM intervention and a control group were selected for the final analysis (N = 3,001 participants). TM was found to reduce emergency room visits [mean difference (MD) -0.70, 95% confidence interval (CI) -1.36 to -0.03], exacerbation-related readmissions (risk ratio 0.74, 95% CI 0.60-0.92), exacerbation-related hospital days (MD -0.60, 95% CI -1.06 to -0.13), mortality (odds ratio 0.71, 95% CI 0.54-0.93), and the St. George's Respiratory Questionnaire (SGRQ) score (MD -3.72, 95% CI -7.18 to -0.26) but did not make a difference with respect to all-cause readmissions, the rate of exacerbation-related readmissions, all-cause hospital days, time to first hospital readmission, anxiety and depression, and exercise capacity. Furthermore, the subgroup analysis by observation period showed that longer TM (≥12 months) was more effective in reducing readmissions. Conclusions: TM can reduce emergency room visits and exacerbation-related readmissions, as well as acute exacerbation (AE)-related hospital days, mortality, and the SGRQ score. The implementation of TM intervention is thus a potential protective therapeutic strategy that could facilitate the long-term management of AECOPD. Systematic Review Registration: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews (number: CRD42020181459).

Gold nanorods conjugated with biocompatible zwitterionic polypeptide for combined chemo-photothermal therapy of cervical cancer.

Combined chemo-photothermal therapy of gold nanorods (GNRs) for cancer treatment shows better therapeutic efficiency than mono-chemotherapy, which has gained worldwide interests of scientists and clinician in both laboratory and clinic application. However, high cytotoxicity, declined delivery efficiency, and unsatisfactory therapy effect of the GNRs are still challenging in anti-cancer treatment. Herein, a series of pH-sensitively zwitterionic polypeptide conjugated GNRs were synthesized via a gold-thiol interaction for combination of chemo-photothermal therapy in cervical cancer treatment. The acid-labile hydrazone bond was utilized to incorporate the doxorubicin (DOX) for pH-sensitive drug release under tumoral environment. The as prepared GNRs conjugates demonstrated pH-triggered surface charge conversion from negative to positive when transporting from blood circulation to tumor extracellular environment, which can facilitate the cellular uptake via electrostatic interaction. After cellular internalization, the drug release was promoted by cleavage of the hydrazone in GNRs conjugates under cancer intracellular acid environment. As the effective near-infrared (NIR) photothermal materials, the as prepared GNRs conjugates can absorb NIR photo energy and convert it into heat under irradiation, which can efficiently kill the tumor cells. In cell assay, the GNRs conjugates displayed excellent biocompatibility against normal cell, enhanced cancer cell uptake, and remarkable cancer cell killing effects. In HeLa tumor-bearing mice, the GNRs conjugates demonstrated enhanced tumor inhibition efficacy by combination of chemo-photothermal therapy.

Metformin regulates inflammation and fibrosis in diabetic kidney disease through TNC/TLR4/NF-κB/miR-155-5p inflammatory loop.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is significantly increasing worldwide, and the incidence of its complications is also on the rise. One of the main complications of T2DM is diabetic kidney disease (DKD). The glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR) increase in the early stage. As the disease progresses, UACR continue to rise and GFR begins to decline until end-stage renal disease appears. At the same time, DKD will also increase the incidence and mortality of cardiovascular and cerebrovascular diseases. At present, the pathogenesis of DKD is not very clear. Therefore, exploration of the pathogenesis of DKD to find a treatment approach, so as to delay the development of DKD, is essential to improve the prognosis of DKD. AIM: To detect the expression of tenascin-C (TNC) in the serum of T2DM patients, observe the content of TNC in the glomerulus of DKD rats, and detect the expression of TNC on inflammatory and fibrotic factors in rat mesangial cells (RMCs) cultured under high glucose condition, in order to explore the specific molecular mechanism of TNC in DKD and bring a new direction for the treatment of DKD. METHODS: The expression level of TNC in the serum of diabetic patients was detected by enzyme-linked immunosorbent assay (ELISA), the protein expression level of TNC in the glomerular area of DKD rats was detected by immunohistochemistry, and the expression level of TNC in the rat serum was detected by ELISA. Rat glomerular mesangial cells were cultured. Following high glucose stimulation, the expression levels of related proteins and mRNA were detected by Western blot and polymerase chain reaction, respectively. RESULTS: ELISA results revealed an increase in the serum TNC level in patients with T2DM. Increasing UACR and hypertension significantly increased the expression of TNC (P < 0.05). TNC expression was positively correlated with glycosylated haemoglobin (HbA1c) level, body mass index, systolic blood pressure, and UACR (P < 0.05). Immunohistochemical staining showed that TNC expression in the glomeruli of rats with streptozotocin-induced diabetes was significantly increased compared with normal controls (P < 0.05). Compared with normal rats, serum level of TNC in diabetic rats was significantly increased (P < 0.05), which was positively correlated with urea nitrogen and urinary creatinine (P < 0.05). The levels of TNC, Toll-like receptor-4 (TLR4), phosphorylated nuclear factor-κB p65 protein (Ser536) (p-NF-κB p65), and miR-155-5p were increased in RMCs treated with high glucose (P < 0.05). The level of TNC protein peaked 24 h after high glucose stimulation (P < 0.05). After TNC knockdown, the levels of TLR4, p-NF-κB p65, miR-155-5p, connective tissue growth factor (CTGF), and fibronectin (FN) were decreased, revealing that TNC regulated miR-155-5p expression through the TLR4/NF-κB p65 pathway, thereby regulating inflammation (NF-κB p65) and fibrosis (CTGF and FN) in individuals with DKD. In addition, metformin treatment may relive the processes of inflammation and fibrosis in individuals with DKD by reducing the levels of the TNC, p-NF-κB p65, CTGF, and FN proteins. CONCLUSION: TNC can promote the occurrence and development of DKD. Interfering with the TNC/TLR4/NF-κB p65/miR-155-5p pathway may become a new target for DKD treatment.

Disulfide Cross-Linked Poly(Methacrylic Acid) Iron Oxide Nanoparticles for Efficiently Selective Adsorption of Pb(II) from Aqueous Solutions.

The efficient selectivity of heavy metal ions from wastewater is still challenging but gains great public attention in water treatment on a world scale. In this study, the novel disulfide cross-linked poly(methacrylic acid) iron oxide (Fe3O4@S-S/PMAA) nanoparticles with selective adsorption, improved adsorption capability, and economic reusability were designed and prepared for selective adsorption of Pb(II) ions in aqueous solution. In this study, nuclear magnetic resonance, dynamic light scattering, scanning electron microscopy, X-ray diffraction, vibrating sample magnetometry, and thermogravimetric analysis were utilized to study the chemophysical properties of Fe3O4@S-S/PMAA. The effect of different factors on adsorption properties of the Fe3O4@S-S/PMAA nanoparticles for Co(II) and Pb(II) ions in aqueous solution was explored by batch adsorption experiments. For adsorption mechanism investigation, the adsorption of Fe3O4@S-S/PMAA for Co(II) and Pb(II) ions can be better fitted by a pseudo-second-order model, and the adsorption process of Fe3O4@S-S/PMAA for Co(II) and Pb(II) matches well with the Freundlich isotherm equation. Notably, in the adsorption experiments, the Fe3O4@S-S/PMAA nanoparticles were demonstrated to have a maximum adsorption capacity of 48.7 mg·g-1 on Pb(II) ions with a selective adsorption order of Pb2+ > Co2+ > Cd2+ > Ni2+ > Cu2+ > Zn2+ > K+ > Na+ > Mg2+ > Ca2+ in the selective experiments. In the regeneration experiments, the Fe3O4@S-S/PMAA nanoparticles could be easily recovered by desorbing heavy metal ions from the adsorbents with eluents and showed good adsorption capacity for Co(II) and Pb(II) after eight recycles. In brief, compared to other traditional nanoadsorbents, the as-prepared Fe3O4@S-S/PMAA with improved adsorption capability and high regeneration efficiency demonstrated remarkable affinity for adsorption of Pb(II) ions, which will provide a novel technical platform for selective removal of heavy metal ions from actual polluted water.

Multisystemic Sarcoidosis Presenting With Leg Ulcers, Pancytopenia, and Polyserositis Was Successfully Treated With Glucocorticoids: A Case Report and Literature Review.

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown etiology. A variety of studies have pointed out that almost every part of the body can be affected, but it most often affected the lungs and intrathoracic lymph nodes. However, cases of sarcoidosis involving multiple organs in one patient are rarely reported. We describe a unique case of sarcoidosis, which was characterized by multiorgan involvement, including leg ulcers, splenomegaly, pancytopenia, and polyserositis. Glucocorticoids were effective during the treatment of the above lesions. This case highlights the diversity of clinical manifestations of sarcoidosis and emphasizes the importance of its differential diagnosis and the periodical follow-up. These are crucial to physicians in the diagnosis and treatment of sarcoidosis. MAIN SYMPTOMS AND IMPORTANT CLINICAL FINDINGS: A 30-year-old male complained about intermittent fever 3 years ago. A computed tomographic scan of the chest showed lymphadenopathy in the mediastinum and hilar regions. Routine blood tests showed leukopenia and mild anemia. The pathologic result of mediastinal lymph node biopsy was granulomatous lesions; thus, the patient was diagnosed with type II sarcoidosis without glucocorticoid therapy. In the following 2 years, the patient suffered from intermittent fever accompanied by dyspnea, fatigue, occasional cough, less sputum, and apparent weight loss. Abnormal physical examinations included leg ulcers and splenomegaly. Laboratory and physical tests revealed pancytopenia, polyserositis, and enlargement of lymph nodes. The pathological findings of leg ulceration, pleura, and left supraclavicular lymph node all suggested granulomas. DIAGNOSIS INTERVENTIONS AND OUTCOMES: It strongly suggested sarcoidosis since tuberculosis, lymphoma, and connective tissue disease were all excluded. Due to severe conditions and multiorgan involvement, we tried to provide methylprednisolone for this patient. After 9 months of oral glucocorticoids therapy, his subjective symptoms as well as hematological and radiological findings were all improved. His leg skin ulceration and scab were also completely disappeared. CONCLUSION: Sarcoidosis has diverse clinical presentations, and many patients present with atypical symptoms. It needs to be timely identified by the clinician and carefully differentiated from other diseases with similar findings so as to make an accurate diagnosis. In this case, the patient had a poor clinical response to glucocorticoids in the early stage of treatment due to the severe condition and multi-organ involvement. It is worth noting that the patient had improved significantly after 9 months of treatment of corticosteroids, which suggested that follow-up is critical.

Malignant Transformation of a Borderline Ovarian Tumor With Pulmonary and Pleural Metastases After Years of Latency: A Case Report and Literature Review.

Borderline ovarian tumor (BOT) refers to a distinct tumor of the ovary of epithelial origin and typically has a favorable prognosis. However, these tumors are not exempt from risks of recurrence and malignant transformation, which can arise from the remaining ovarian tissue, peritoneal implants, or distant localization. Here, we report a case of a mucinous BOT with multiple pulmonary cystic nodules without evidence of pulmonary metastasis even after two fine needle biopsies. Staging surgery was performed, and no evidence of peritoneal implants or invasion to adjacent organs found. At the end of the 7-year monitored follow-up after surgery, the pulmonary lesions were found to be increased in size. The transbronchial lung biopsy and pleural biopsy confirmed transformation into malignant mucinous adenocarcinoma with pleural metastasis. In the current case, we observed potential pulmonary metastasis of the BOT with malignant transformation and a latency as long as 7 years, which reminds us that multiple pulmonary cystic changes in patients with BOTs should be screened carefully to evaluate the pulmonary involvement of BOTs and potentially false-negative results after fine needle biopsy. Thus, a thorough check-up for complete staging of the disease and a close long-term follow-up to monitor potential recurrence and malignant transformation are advised.

Anti-inflammation effects of the total saponin fraction from Dioscorea nipponica Makino on rats with gouty arthritis by influencing MAPK signalling pathway.

BACKGROUND: Dioscorea nipponica Makino is widely used in traditional Chinese medicine to treat gouty arthritis. METHODS: Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). HE staining was used to detect the histopathologic changes of the synovial tissue of joint. Immunohistochemical method was used to detect the protein expressions of P-38, p-P38, JNK, p-JNK, ERK1/2, p-ERK1/2, MEK1/2, p-MEK1/2, MKK4, p-MKK4, ICAM1, VCAM1, and PPARγ in the synovial tissue of joint. Realtime PCR and WB methods were used to detect the mRNA and protein expressions of PPARγ and AdipoR2 in the synovial tissue of joint. The contents of CXCL1 and ADP in the blood serum were measured by Elisa method. RESULTS: Our study showed that RDN could improve the situation of the synovial tissue, reduce the protein expressions of MKK4, p-MEK1/2, p-JNK, p-ERK1/2, ICAM1. They could also decrease the content of CXCL1 and increase the content of ADP in the blood serum. CONCLUSION: RDN has good effect of anti-inflammation. This is in part realized by influencing MAPK signalling pathway. It provides a new visual angle to reveal the mechanism of RDN to treat GA.

Effects of 2,3',4,4',5-pentachlorobiphenyl exposure during pregnancy on DNA methylation in the testis of offspring in the mouse.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants, and the widespread use of PCBs has had adverse effects on human and animal health. This study experiment explored the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on the mammalian reproductive system. PCB118 was administered to pregnant mice from 7.5 to 12.5 days of gestation; F1 mice were obtained and the reproductive system of F1 male mice was examined. PCB118 damaged the reproductive system in male F1 mice, as evidenced by negative effects on the testicular organ coefficient (testes weight/bodyweight), a decrease in the diameter of seminiferous tubules and a significant reduction in the anogenital distance in 35-day-old F1 mice. In addition, methylation levels of genomic DNA were reduced, with reductions in the expression of the DNA methyltransferases DNMT1, DNMT3A and DNMT3B, as well as that of the epigenetic regulatory factor ubiquitin like with PHD and ring finger domains 1 (Uhrf1). Together, the results of this study provide compelling evidence that exposure of pregnant mice to PCB118 during primordial germ cell migration in the fetus affects the reproductive system of the offspring and decreases global methylation levels in the testis.

Endoscopic submucosal dissection of tracheal deep benign fibrous histiocytoma using hybrid knife.

Deep benign fibrous histiocytoma (FH) is an uncommon and poorly recognized tumor that arises in subcutaneous or deep soft tissue. Deep benign FH of the trachea is even more rare. Deep benign FH recurs in approximately 20% of cases, so surgical resection is the recommended treatment for FH. However, some patients are afraid of the trauma and potential complications from the resection of tracheal tumors, so they do not accept surgical resection. With the development of interventional pulmonology, bronchoscopic intervention plays a key role in the treatment of benign tracheal tumors. Novel tools have emerged in interventional pulmonology and optimized the traditional techniques. Here, we report a case of deep benign FH of the trachea with broad base relapse after electrocautery with snare, argon plasma coagulation (APC) and radiotherapy. It was treated successfully by endobronchial resection with a hybrid knife (HK) and APC. The HK is a hybrid device that combines an electrocautery knife with a water jet in one instrument. Submucosal injection and circumferential cutting and dissection of lesions as well as coagulation of bleeding can be performed only with the HK. During the 6 months follow-up, the deep benign FH of the trachea did not relapse. In the case reported herein, the HK enabled submucosal injection and circumferential cutting and dissection of lesions as well as access to submucosal lesions to gain further adequate APC treatment, thereby allowing a better clinical response than that achieved by traditional electrocautery with snare and APC. In conclusion, the HK with a water jet is a feasible and effective endoscopic method for management for benign or low-grade malignant neoplasms of the trachea, especially those with a wide base and submucosal involvement.

A comparative study of the five-repetition sit-to-stand test and the 30-second sit-to-stand test to assess exercise tolerance in COPD patients.

Purpose: The sit-to-stand test (STST) has been used to evaluate the exercise tolerance of patients with COPD. However, mutual comparisons to predict poor exercise tolerance have been hindered by the variety of STST modes used in previous studies, which also did not consider patients' subjective perceptions of different STST modes. Our aim was to compare the five-repetition sit-to-stand test (5STS) with the 30-second sit-to-stand test (30STS) for predicting poor performance in the six-minute walking test and to evaluate patients' subjective perceptions to determine the optimal mode for clinical practice. Patients and methods: Patients with stable COPD performed 5STS, 30STS and the 6MWT and then evaluated their feelings about the two STST modes by Borg dyspnea score and a questionnaire. Moreover, we collected data through the pulmonary function test, mMRC dyspnea score, COPD assessment test and quadriceps muscle strength (QMS). A receiver operating characteristic curve analysis of the 5STS and 30STS results was used to predict 6-minute walk distance (6MWD) <350 m. Results: The final analysis included 128 patients. Similar moderate correlations were observed between 6MWT and 5STS (r=-0.508, P<0.001) and between 6MWT and 30STS (r=0.528, P<0.001), and there were similar correlations between QMS and 5STS (r=-0.401, P<0.001) and between QMS and 30STS (r=0.398, P<0.001). The 5STS and 30STS score cutoffs produced sensitivity, specificity and positive and negative predictive values of 76.0%, 62.8%, 56.7% and 80.3% (5STS) and 62.0%, 75.0%, 62.0% and 75.0% (30STS), respectively, for predicting poor 6MWT performance. The 5STS exhibited obvious superiority in terms of the completion rate and the subjective feelings of the participants. Conclusion: As a primary screening test for predicting poor 6MWD, the 5STS is similar to the 30STS in terms of sensitivity and specificity, but the 5STS has a better patient experience.