[An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix].

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 µL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.

Nondestructive determination of SSC in an apple by using a portable near-infrared spectroscopy system.

The soluble solids content (SSC) is an important factor in the internal quality detection of apples. It is essential to have reliable and high-speed measurement of the SSC. However, almost all traditional equipment is inconvenient and expensive. We designed a handheld nondestructive SSC detector based on near-infrared (NIR) spectroscopy, which is composed of a portable NIR spectrometer, cloud server, smartphone app, and prediction model of SSC. We preprocessed the spectrum with multiplicative scatter correction (MSC), standard normal variable transformation (SNV), and Savitzky-Golay (S-G) smoothing algorithms. Besides, the linear weight reduction of the particle swarm optimization algorithm is carried out, and we establish the model of an extreme learning machine optimized with the improved particle swarm optimization (IPSO-ELM) algorithm. The R2, root mean square error of prediction (RMSEP), and residual prediction deviation (RPD) of the model are 0.993, 0.0155, and 11.6, respectively, which are better than the traditional model obviously. In addition, the number of wavelengths reduced from 228 to 70 as the model is simplified with the uninformative variable elimination (UVE) method. The time of training is reduced by 29.30% compared with the original spectrum. It can be verified that the IPSO-ELM model has good prediction performance, and the NIR diffuse reflectance spectroscopy is a reliable nondestructive measurement of SSC in apples.

Genistein Up-Regulates the Expression of EGF and E-Cadherin in the Treatment of Senile Vaginitis.

Investigating the therapeutic effect of genistein (Gen) on postmenopausal senile vaginitis (SV) and its mechanism of action. Adult SPF female Wistar rats were selected to establish a bilateral ovariectomized animal model (OVX), which simulated senile vaginitis dominated by estrogen deficiency in ovarian dysfunction. After 14 days of continuous treatment, the morphology of vaginal epithelial tissue was observed and various types of epithelial cells were counted, and the body mass and uterine and vaginal index of rats were measured. the levels of vaginal tissue secretion, microorganism, hormone and glycogen in each group were measured and the reproductive health was evaluated clinically. The protein expression and mRNA expression of epidermal growth factor (EGF) and E-cadherin (E-cadherin) in vaginal tissues were detected by immunohistochemistry and RT-PCR, respectively. Result showed that Genistein lowered vaginal pH, increased vaginal index and vaginal health score, thickened epithelial layers and improved vaginal tissue atrophy after administration. Genistein also increased the contents of glycogen and Lactobacillus in vagina, and promoted the expression of EGF, E-cadherin protein and mRNA. To sum up, there is no significant change in serum E2 and FSH levels, indicating that genistein has no effect on hormone levels in rats. genistein promoted the proliferation of vaginal epithelial cells, thickened epithelial layers and the vaginal wall, which improved the resistance of vaginal epithelium, the recovery of self-cleaning ability and healed the vaginal wound and erosive surface to improve atrophy.

Evolution of dissolved organic matter during artificial groundwater recharge with effluent from underutilized WWTP and the resulting facilitated transport effect.

Currently, the interaction between contaminants and dissolved organic matter (DOM) during artificial groundwater recharge (AGR) with effluent from underutilized wastewater treatment plant (WWTP) is unclear. The present study investigated DOM evolution in this AGR scenario. The DOM composition in the inflow was identified to be distinct to that of the outflow due to the release of soil humic acid (HA). The soluble soil HA was then extracted and used in co-transport experiments with tetracycline (TC). The separated HA transport through the soil column exhibited high mobility with mass recovery >92.5% in the effluent. Following the mixing of injected TC and HA, the TC breakthrough in the column increased with HA concentration. TC was heavily adsorbed by the soil without the presence of HA, yet the retention ratios decreased from 63.60% to 53.30% for the HA range of 0-20 mg L-1. An advection-dispersion-retention (ADR) numerical model was developed to effectively quantify the HA-TC co-transport, with results demonstrating the reduction in the TC attachment rate with increasing HA concentrations. Furthermore, batch adsorption experiments, kinetics and isotherms models, and FTIR spectra analysis were implemented to determine the underlying mechanism. The co-transport behavior was observed to be a function of the relative soil sorption affinity between HA and TC. The weaker sorption of the HA-coated TC compared to the separated TC consequently suggests that HA is likely to compete for available soil adsorption sites. Thus, the release of soil humus during AGR can potentially facilitate the transport of the introduced contaminants.

[Effect of baicalin on expression of fibrogenic factors TGF-ß1, mmp2 and timp2 in tissue of mice with pulmonary fibrosis].

To investigate the effect of baicalin extracted from Qinbai Qingfei Concentrated Pills on the expressions of TGF-ß1, mmp2 and timp2 in mice with pulmonary fibrosis induced by bleomycin. The Biacore technique was used to detect the specific binding between Qinbai Qingfei Concentrated Pills and TGF-ß1, and the affinity components were enriched, regenerated and recovered by Biacore fishing. Then ultra-performance liquid chromatography and quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) were used to determine whether the monomer was baicalin. Biacore was used to verify the affinity kinetics of baicalin, which was validated by pharmacodynamics in vivo. Totally 30 BALB/C mice were randomly divided into three groups: baicalin group, blank group and model group. The blank group was given sodium chloride injection(0.08 mL·kg~(-1)), while the model group and the baicalin group were injected with 4 mg·kg~(-1) bleomycin. The localization of TGF-ß1, mmp2 and timp2 protein in the cells and the mRNA expressions of TGF-ß1, mmp2 and timp2 were detected by RT-PCR 14 days later. The results of Biacore affinity analysis showed that the peak of binding response between Qinbai Qingfei Concentrated Pills and TGF-ß1 protein reached 1 524.0 RU, with specific binding. The affinity constant K_D of baicalin and TGF-ß1 was 1.620 06 µmol·L~(-1), which was determined by SPR kinetic analysis, suggesting a stable binding between baicalin and TGF-ß1, which verified the results of angulation. The results of immunohistochemistry showed that the deposition of cellulose in baicalin group was significantly less than that in model group, the mRNA expressions of TGF-ß1, mmp2 and timp2 were decreased in baicalin solution compared with the model group. Baicalin combined with TGF-ß1 could inhibit the expressions of mmp2 and timp2 and delay the progress of pulmonary fibrosis.

[Effect of Dilong on expression of fibrogenic factors TGF-ß1 and α-SMA in lung tissue of mice with pulmonary fibrosis].

The aim of this paper was to investigate the effect of Dilong( geosaurus) on the expressions of fibrotic factors TGF-ß1 and α-SMA in bleomycin-induced pulmonary fibrosis mice. The binding ability of Dilong to fibrotic factor TGF-ß1 was initially detected by Biacore technology and verified by in vivo pharmacodynamics. A total of 60 SPF C57 mice were randomly divided into 6 groups. Except the blank group( injecting 0. 08 m L·kg-1 sodium chloride in the trachea),the other five groups were given bleomycin( 4 mg·kg-1) to replicate the pulmonary fibrosis model. After 14 days of drug treatment,the expressions of TGF-ß1 and α-SMA were detected by Masson staining,immunohistochemistry and RT-PCR. The results of Biacore experiment showed that the extract of Dilong was well bound to TGF-ß1 protein in vitro,and the binding value reached 619. 3. Compared with the model group,Masson's results showed that cellulose deposition in high-dose,medium-dose and low-dose Dilong groups decreased to varying degrees. RT-PCR results showed that different doses of Dilong could reduce protein and mRNA expressions of TGF-ß1 and α-SMA to a certain extent in a dose-dependent manner. In conclusion,Dilong could delay the process of pulmonary fibrosis by binding to target protein TGF-ß1 and inhibiting the expression of α-SMA.

Fabrication of broadband anti-reflective layers by mask-free etching TiO2 films.

We present a simple way to make TiO2 anti-reflective layers on top of silicon substrates. Surfaces of TiO2 films have been modified by radio frequency plasma with CF4 as an etchant. Mask-free etching process on the polycrystalline films leads to the formation of random sub-wavelength textures. The reflection of the etched samples are significantly suppressed in the wavelength range of 400~800 nm (2.9~4.6%, 3% compared with 34% on bare silicon at the wavelength of 600 nm). We have numerically simulated the optical properties of TiO2 layers using the finite-difference time-domain method. The anti-reflective effects are attributed to random roughness on TiO2 surfaces. The etching porcess increases the surface roughness, therefore, the gradient of refractive index between air and silicon substrate is reduced. As a result, the Fresnel reflection is supressed. Our results demonstrate an efficient way of anti-reflective coating for solar cells.

Comparison of the chemical profiles of fresh-raw and dry-processed Juglans mandshurica.

The processing of Juglans mandshurica Maxim. is important to reduce its toxicity and enhance its efficacy. Simple, efficient, and sensitive ultra-high performance liquid chromatography coupled with a time-of-flight mass spectrometry based chemical profiling approach was proposed to rapidly evaluate the chemical difference between fresh and dry samples. Under the optimized ultra-high performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry conditions, 81 significantly different compounds were rapidly discovered using principal component analysis, and then tentatively identified by comparison with reference substances or inferred through mass spectral fragment ion analysis and literature data. These compounds included 35 naphthoquinones, 11 diarylheptanoids, nine flavonoids, eight triterpenes, 12 phenolic acids, and six aliphatics. The results demonstrated that chemical reactions occurring during processing could be used to elucidate the processing mechanism of Juglans mandshurica Maxim. This study provides a novel approach to identifying complicated components of various complex mixtures in fresh-raw and dry-processed traditional Chinese medicines, which could be used as a valid analytical method to further understand the processing mechanisms of these medicines, as well as providing intrinsic quality control of the medicines and their processed products.

Isolated leukemic infiltration of peripheral nervous system.

INTRODUCTION: Isolated leukemic infiltration of peripheral nerves without central nervous system involvement, or isolated neuroleukemiosis, is an extremely rare complication of leukemia. METHODS: We report the case of a patient with isolated neuroleukemiosis and review the pertinent literature. RESULTS: A man with a 12-year history of acute monoblastic leukemia presented with median mononeuropathy. Magnetic resonance imaging revealed a thickened median nerve. Nerve biopsy confirmed the diagnosis of leukemic infiltration. Clinical resolution was achieved through local radiation. Only 10 cases of isolated neuroleukemiosis have been reported. Most were in remission from leukemia. Our patient is the only one who was considered clinically cured of leukemia. CONCLUSIONS: The presumed pathophysiology of isolated neuroleukemiosis is hematogenous spread of leukemic cells into the peripheral nervous system across the blood-nerve barrier. It should be considered in the differential diagnosis in patients with leukemia who present with neuropathy, even when they are considered to be clinically cured of leukemia.

The association of physical activity and sedentary behavior with depression in US adults: NHANES 2007-2018.

Objectives: Depression is largely preventable, and strategies that can effectively suppress its development are imperative. We aimed to examine whether physical activity and sedentary behavior were associated with depression and explore the possible mediatory role of complete blood count in this association. Methods: In this cross-sectional study, data were integrated from the National Health and Nutrition Examination Study (2007-2018). Depression was defined using the Patient Health Questionnaire-9. The risk for depression, expressed as odds ratio (OR) and 95% confidence interval (CI), was quantified by survey-weighted logistic regression analyses. Results: A total of 31,204 respondents were analyzed. Significance was identified for all, except walking or bicycling per week, types of physical activity, and sedentary behavior. Per 1 standard deviation (SD) increment in metabolic equivalent of task (MET) of weekly vigorous recreational physical activity was associated with 31.3% decreased depression risk (adjusted OR: 0.687, 95% CI: 0.5663-0.840). Per 1 SD increment in sitting time can increase depression risk by 22.4% (adjusted OR: 1.224, 95% CI: 1.131-1.325). In subsidiary analyses, the association with depression was reinforced in respondents aged ≤65 years and those overweight or obese. Mediation analyses revealed significant effects for red blood cell (RBC) on total MET (19.4%) and moderate work-related physical activity (MWPA) (22.0%), and for red cell distribution wide (RCDW) on vigorous work-related physical activity (17.7%), moderate work-related physical activity (13.1%), total MET (11.2%), and sitting time (16.4%) (p < 0.01). Conclusion: Our findings indicate that more physical activity and less sitting time were associated with a lower likelihood of having depression among US adults, and this association was probably mediated by RBC and RCDW.

Artesunate reduces sepsis-mediated acute lung injury in a SIRT1-dependent manner.

Introduction: Sepsis-mediated acute lung injury (ALI) is a critical clinical condition. Artesunate (AS) is a sesquiterpene lactone endoperoxide that was discovered in Artemisia annua, which is a traditional Chinese herb. AS has a broad set of biological and pharmacological actions; however, its protective effect on lipopolysaccharide (LPS)-induced ALI remains unclear. Methods: LPS-mediated ALI was induced in rats through bronchial LPS inhalation. Then NR8383 cells were treated with LPS to establish an in vitro model. Further, we administered different AS doses in vivo and in vitro. Results: AS administration significantly decreased LPS-mediated pulmonary cell death and inhibited pulmonary neutrophil infiltration. Additionally, AS administration increased SIRT1 expression in pulmonary sections. Administration of a biological antagonist or shRNA-induced reduction of SIRT1 expression significantly inhibited the protective effect of AS against LPS-induced cellular injury, pulmonary dysfunction, neutrophil infiltration, and apoptosis. This demonstrates that enhanced SIRT1 expression is crucially involved in the observed protective effects. Conclusion: Our findings could suggest the use of AS for treating lung disorders through a mechanism involving SIRT1 expression.

Modulation of P1 and EGF expression by Baicalin.

Mycoplasma pneumoniae (M. pneumoniae) is increasingly recognized as a major cause of acute respiratory tract infections. Today, macrolides are used in the primary treatment of M. pneumoniae infection. However, with the increasing prevalence of strains resistant to macrolides, as well as reports of toxicity and adverse side effects, it is necessary to develop an alternative therapeutic agent. A compound recipe - Qinbaiqingfei pellets (Qinbai) - have already been approved in China as the first effective traditional Chinese medicine to be used against M. pneumoniae. Herein, we characterize the mechanism by which Qinbai interacts with M. pneumoniae and lung epithelial cells. The fact that Baicalin is the key component of Qingbai leads us to believe its study is important to elucidating the mechanism of the action of Qinbai. In this study, we describe the complex impact of Baicalin on the adhesin protein P1 of M. pneumoniae and on the expression of epidermal growth factor (EGF) in BALB/c mice and A549 cells infected with M. pneumonia. We draw the conclusion that Baicalin not only cured M. pneumoniae infection by inhibiting P1 expression, but also enhanced the repair of lung epithelial cells by upregulating EGF. Finally, we demonstrate that Baicalin plays a role in Qinbai treatment.

[The clinical therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization in treating primary liver cancer with pulmonary metastases].

OBJECTIVE: To observe the therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization on treatment of primary liver cancer with pulmonary metastases. METHODS: Sixty patients were randomly divided into two groups: group A (treatment group, n = 30) and group B (control group, n = 30). Group A was received periodic transcatheter arterial chemoembolization (TACE) and 10 mg arsenic trioxide by intravenous infusion for 5 hours per day, 3 days after TACE. Each cycle consisted of 14 days' administration, and repeated after 2 weeks. Each patient was received 3-4 successive cycles. Group B was received periodic TACE alone. OBJECTIVE: efficiency, benefit rate, quality of life and the correlates with metastatic tumor size and number in the both groups were recorded. RESULTS: The objective efficiency was 26.7% (8/30), and the benefit rate was 60.0% (18/30) in group A, while they were 0 and 16.7% (5/30) in group B with significant statistics differences (χ(2) = 7.067, P = 0.008; χ(2) = 11.915, P = 0.001). The quality of life was improved in 4 patients and stable in 18 of group A, while no patient was improved and 13 were stable in group B (χ(2) = 9.669, P = 0.008). There was a significantly positive correlation between the tumor burden and therapeutic effect (Kendall r = -0.765, P < 0.001; Spearman r = -0.821, P < 0.001). CONCLUSION: Arsenic trioxide combined TACE is an effective treatment method in treating primary liver cancer with pulmonary metastases.

Effect of transjugular intrahepatic portosystemic shunt combined with 125I particle implantation on portal vein tumor thrombus in hepatocellular carcinoma.

OBJECTIVE: The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with 125I particle implantation in the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma was discussed and analyzed in this study. METHODS: A total of 127 patients with primary hepatocellular carcinoma (PHC) complicated with PVTT admitted to our hospital from March 2017 to June 2018 were enrolled. The patients were classified into an observation group (n=69) and a control group (n=58) in the light of the different treatment methods. The control group patients were treated with TIPS alone, and the observation group patients received 125I particle implantation on the basis of TIPS in the control group. Subsequently, the clinical therapeutic efficacy, perioperative indicators, postoperative complications, quality of life and survival of patients before and after treatment were compared between the two groups. RESULTS: The remission rate in the observation group was remarkably higher than that of the control group (P<0.05), and the difference in the overall response rate (ORR) of the two groups of patients was not statistically significant (P>0.05). The AFP, PLT, WBC and the diameter of the main portal vein in the two groups dropped substantially compared to those before treatment (P<0.05), and the AFP and the diameter of the main portal vein in the observation group were notably lower than those in the control group (P<0.05). After treatment, the ALT, AST and TBiL of the two groups were remarkably higher than those before treatment (P<0.05), and these indicators in the observation group were apparently higher than those in the control group (P<0.05). There was no significant difference in the incidence of postoperative gastrointestinal bleeding, fever, granulocytopenia and abnormal hepatic dysfunction between the observation group and the control group (P>0.05). The functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores of the two groups 6 months after operation was substantially lower than pre-op scores (P<0.05), and the observation group had apparently lower postoperative scores than the control group (P<0.05). The progression-free survival (PFS) and overall survival (OS) in the observation group were critically superior to those in the control group (P<0.05). CONCLUSION: TIPS combined with 125I particle implantation in the treatment of PHC patients with PVTT can help improve patients' clinical treatment efficacy after surgery while prolonging their postoperative survival. The treatment is safe and worthy of clinical promotion.

The Protective Activity of Penehyclidine Hydrochloride against Renal Ischemia/Reperfusion-Mediated NLRP3 Inflammasome Activation is Induced by SIRT1.

Background: The activation of alveolar macrophages (AMs) modulated via leucine-rich repeat (NLR) pyrin domain containing 3 (NLRP3) inflammasome activation is key to the progression of renal ischemia/reperfusion (rI/R)-mediated acute lung injury (ALI). Sirtuin-1 (SIRT1) can attenuate NLRP3 inflammasome activation during I/R stress and may be an important mechanism underlying ALI pathogenesis. Penehyclidine hydrochloride (PHC), an anticholinergic drug, exerts protective effects against rI/R-mediated ALI. This study aimed to decipher the effects of PHC on SIRT1 activation and the underlying mechanism of the protective activity of PHC against rI/R-mediated ALI.Materials and methods: We used an ALI rat model and the rat AMs cell line NR8383 to assess the degree of lung injury in vivo and in vitro.Results: The results show that PHC attenuates rI/R-mediated lung injury indices, myeloperoxidase, and apoptosis in vivo. It decreases the rI/R-mediated release of prostaglandin E2 and nitric oxide, mitochondrial reactive oxygen species production, and the activity of NADPH oxidase-4 in vitro. PHC ameliorates the rI/R-induced activation of the thioredoxin-interacting protein, caspase 1 (P10 unit), and NLRP3 inflammasome, along with reduced activation of interleukin-1ß and interleukin-18 in vitro. We show that PHC alleviates the rI/R-induced reduction of SIRT1 and the depletion of SIRT1 eliminates the ameliorating activity of PHC on the NLRP3 inflammasome activation in vitro. Conclusions: In summary, the findings suggest that PHC ameliorates the rI/R-mediated ALI through the SIRT1-mediated NLRP3 inflammasome activation.

The antifibrotic effect of pheretima protein is mediated by the TGF-ß1/Smad2/3 pathway and attenuates inflammation in bleomycin-induced idiopathic pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pheretima is a traditional Chinese medicine that could treat various lung diseases such as asthma, pneumonia, and lung cancer effectively; however, limited studies on the use of Pheretima protein in the treatment of lung diseases have been conducted to date. AIM OF THE STUDY: The aim of this study was to explain the antipulmonary fibrosis mechanism of the Pheretima protein and elucidate its possible cell signaling pathways. MATERIAL AND METHODS: Fresh pheretima was freeze-dried to obtain the Pheretima protein. Divide C57BL/6 mice into control and bleomycin (BLM)-induced models, pirfenidone, and Pheretima protein-treatment groups. Three weeks later, they were treated with H&E and Masson's trichrome staining to assess lung injury and fibrosis. Pulmonary fibrosis was assessed using immunohistochemistry (IHC), realtime-PCR (RT-PCR), and western blotting. Inflammation was assessed using the alveolar lavage fluid. RESULTS: Pheretima protein inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition and reduced inflammation. It also reduced the levels of Smad2/3, pSmad2/3, and transforming growth factor-beta 1 (TGF-ß1). Thus, our results indicate that Pheretima protein can alleviate BLM-induced pulmonary fibrosis in a mouse model. CONCLUSION: Pheretima protein inhibits ECM, EMT, and antiinflammatory markers, which in turn ameliorates BLM-induced pulmonary fibrosis. Preliminary mechanistic studies indicated that Pheretima protein can exert its biological activity by downregulating the TGF-ß1/Smad2/3 pathway.

The Effectiveness of Wogonin on Treating Cough Mice With Mycoplasma Pneumoniae Infection.

Background: Cough is the main symptom of mycoplasma pneumoniae (MP) infection. Cough potential protein transient receptor potential A1 (TRPA1) plays an important role in cough reflex. The purpose of this study was to clarify the mechanism of wogonin, the effective component of Qinbai Qingfei concentrated pellet (Qinbai), in the treatment of cough after MP infection. Methods: The Biacore™ system was used to detect whether there was specific binding between Qinbai and cough potential protein TRPA1. Biacore™ fishing technology and UPLC-Q-TOF-MS technology were used during fishing combined active components and identification and analysis of recovered samples. The expression levels of TRPA1, substance P (SP), calcitonin gene-related peptide (CGRP), cough-related proteins, and mRNA in the lung tissues from each group were detected by immunohistochemistry, Western blot, and real-time PCR. Results: Biacore™ results showed that Qinbai had strong specific binding to TRPA1 protein with a binding value of 99.0 resonance unit (RU). The samples obtained from angling were identified and analyzed by UPLC-Q-TOF-MS as wogonin. The results of immunohistochemistry, Western blot, and real-time PCR showed that compared with the model group, the wogonin group had lower expressions of mRNA, TRPA1, SP, and CGRP in the lung tissue of cough mice with MP infection (p < 0.01 or p < 0.05), and the effects were superior to those of azithromycin and pentoxyverine control groups. Conclusion: Wogonin can treat cough after MP infection by affecting the expressions of cough-related proteins, such as TRPA1, SP, and CGRP. This study provided a theoretical foundation for the clinical research of Qinbai.

Pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives as RAF-MEK-ERK pathway signaling pathway blockers: Synthesis, cytotoxic activity, mechanistic investigation and structure-activity relationships.

The constitutive activation of ERK1/2 (RAF-MEK-ERK) signaling pathway has been widely observed in many types of tumors, and the blockade of ERK1/2 signaling pathway has been proved to reduce tumor growth. Therefore, ERK1/2 signaling pathway has become an interesting therapeutic target for cancer therapy. Despite the successful development of BRAF and MEK inhibitors in clinic treatment, resistance often appears to re-enhance ERK1/2 signaling. Here we report the design, synthesis, biological activity of a series of novel pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives based on compound 1. Among them, the target compound N-(3-chlorophenyl)-2-((1,3-dimethyl-7-(4-methylpiperazin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl)amino)acetamide (14m) exhibited excellent antiproliferative activity towards MCF-7, A375, SK-MEL-2 and SK-HEP-1 cells, with low cytotoxicity in C28/I2 cells. Tumor spheroid assay demonstrated the superior potency of 14m in inhibiting the growth of SK-HEP-1 spheroidal models. The mechanism of 14m to induce cancer cell death was shown to suppress cell migrations, induce cell apoptosis, decrease the levels of phosphorylated ERK and MEK in a dose-dependent manner and increase ROS production.

Design, Synthesis, and Biological Activity of a Novel Series of 2-Ureidonicotinamide Derivatives Against Influenza A Virus.

BACKGROUND: Viral resistance to existing inhibitors and the time-dependent effectiveness of neuraminidase inhibitors have limited the number of antivirals that can be used for prophylaxis and therapeutic treatment of severe influenza infection. Thus, there is an urgent need to develop new drugs to prevent and treat influenza infection. OBJECTIVE: The aims of this study was to design and synthesize a novel series of 2-ureidonicotinamide derivatives and evaluate their anti-IAV activities. Furthermore, we predicted the abilities of these compounds to inhibit the PA-PB1 subunit and forecasted the docking poses of these compounds with RNA polymerase protein (PDB ID 3CM8). METHODS: The novel designed compounds were synthesized using classical methods of organic chemistry and tested in vitro for their abilities inhibiting RNP and against influenza A virus. In addition, the 23 synthesized molecules were subjected to the generated pharmacophore Hypo1 to forecast the activity target PA-PB1 subunit of RNA polymerase. The ADMET pharmacokinetic parameters were calculated by the ADMET modules in Discovery Studio 2016. The docking results helped us demonstrate the possible interactions between these compounds with 3CM8. RESULTS: The synthesized 2-ureidonicotinamide derivatives were characterized as potent anti-influenza inhibitors. The target compounds 7b and 7c demonstrated significant antiviral activities and could be considered as novel lead compounds of antiviral inhibitors. In addition, compound 7b revealed suitable ADME properties expressed and might be a significant RNA polymerase inhibitor targeting the PA-PB1 subunit based on the predictable results and the docking results. CONCLUSION: This study revealed a novel series of compounds that might be useful in the search for an effective drug against the influenza virus.

Predictive value of the ratio of venoarterial PCO2 to arteriovenous O2 content difference for organ injury in patients with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a common but severe disease with high mortality. Organ injury is the primary risk factor for death in SAP patients. The purpose of this study was to explore the predictive value of the ratio of venoarterial PCO2 to arteriovenous O2 content difference [P(cv-a)CO2/C(a-cv)O2] for organ injury in patients with SAP to provide evidence for further clinical intervention. METHODS: We retrospectively collected data from 108 patients with SAP admitted to Huzhou Central Hospital between January 2018 and January 2021. Forty-five patients who experienced organ injury were defined as the organ injury group, and 63 patients without organ injury were defined as the control group. The differences in P(cv-a)CO2/C(a-cv)O2, lactate, hematocrit (HCT), Acute Physiology and Chronic Health Evaluation (APACHE II) scores, and Ranson scores between the two groups were analyzed, and a receiver operating characteristic curve (ROC) was used to analyze the value of P(cv-a)CO2/C(a-cv)O2 in the prediction of organ injury in SAP patients. RESULTS: At admission, the organ injury group demonstrated significantly higher Ranson scores and APACHE II scores than the control group (Ranson scores: 6.09±1.35 vs. 3.97±2.02, respectively, P=0.000; APACHE II scores: 11.64±2.91 vs. 10.08±2.91, respectively, P=0.007). The value of P(cv-a)CO2/C(a-cv)O2 was also elevated compared to the control group (1.47±0.41 vs. 1.09±0.33, respectively, P=0.000) as was the level of lactate (3.33±0.86 vs. 2.56±0.70 mmol/L, respectively, P=0.000). There was no significant difference in HCT between the two groups at admission (44.47%±6.29% vs. 44.53%±5.75%, respectively, P=0.957). The Ranson score, APACHE II score, P(cv-a)CO2/C(a-cv)O2 and lactate levels were all significant predictors of organ injury in patients with SAP. The area under the curve of P(cv-a)CO2/C(a-cv)O2 was 0.733 (0.637-0.829), P=0.000. CONCLUSIONS: P(cv-a)CO2/C(a-cv)O2 is a potential predictor of organ injury in patients with SAP.