Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) comprise an effective therapy for advanced non-small cell lung cancer patients with EGFR-activating mutations. Unfortunately, most patients eventually develop resistance to EG-FR-TKIs, probably due to a secondary point mutation of EGFR T790M. Thus, a sensitive method for accurate detection of T790M mu-tation is essential. Peripheral blood detection has gained our attention because it is convenient, making dynamic noninvasive quantita-tive detection of T790M mutation an optimal means of monitoring the efficacy of EGFR-TKIs. To date, the clinical significance of T790M mutation and EGFR-TKI resistance remains controversial. Several EGFR-TKIs targeting EGFR mutation, which have been in-troduced in recent years, showed better response in patients with T790M mutation, indicating that T790M may be a biomarker for con-quering resistance. This review introduces the methodology of T790M detection and its role in clinical practice.

In the era of outbreaking of antibiotic resistance, the discovery of new antibacterial drugs is emergent.Antimicrobial peptides are important components of the natural defenses of most living organisms against invading pathogens.The unique antibacterial mechanism, direct bactericidal effect, relatively slow of resistance acquirement, and can used alone or combined with antibiotics, make antimicrobial peptides be attractive potential antibacterial drugs.In this paper, we review the physicochemical property of antibacterial peptides, action mechanism and design of antimicrobial peptides, and give a brief introduction of several promising antimicrobial peptides.

OBJECTIVE: Although rare, invasive rhino-orbital-skull base aspergillosis usually is fatal and necessitates prompt diagnosis, surgical intervention and antifungal treatment. METHOD: A case series of 5 patients, with review of treatments and outcomes. RESULT: Five patients initially presented with orbital apex syndrome without apparent rhino-sinus disease. Histologic examination revealed invasive aspergillosis. Four patients underwent transnasal endoscopic surgical exploration of rhino-orbital-skull base, and three of them simultaneously underwent optic nerve decompression. One patient underwent the rhinopharyngeal biopsy. Following surgical debridement and antifungal drug, Two patients achieved various degree of recovery, 1 patient (case 5) showed vision improvement, from counting fingers to 0.1 and symptom-free during 65 months follow-up. One patient (case 1) showed no recovery of vision from no light perception, but symptom-free during 43 months follow-up. Other three patients respectively died of massive intracranial spread (case 3), postoperative brainstem hemorrhage (case 2) and sepsis (case 4). CONCLUSION Invasive sino-orbital-skull base aspergillosis often may resemble inflammatory conditions. Early diagnosis and surgical intervention are required to improve vision and survival. The endoscopic surgical exploration and biopsy often are necessary to rule out fungal sinus infection before considering steroid use, especially in immunocompromised individuals. The patients with invasive rhino-orbital-skull base aspergillosis usually have a poor prognosis.
Adult ; Aged ; Aspergillosis ; pathology ; Female ; Humans ; Male ; Middle Aged ; Orbit ; microbiology ; Orbital Diseases ; etiology ; metabolism ; Retrospective Studies ; Sinusitis ; microbiology ; Skull Base ; microbiology

OBJECTIVE: To detect the effect of p38 mitogen activated protein kinase (p38MAPK) and cyclooxygenase-2 (COX-2) on the expression of mucin5AC (MUC5AC) in human nasal mucosa induced by histamine in vitro, and to investigate the pathogenesis of mucus hypersecretion in allergic rhinitis (AR). METHOD: Western blot was performed to detect the protein expressions of p38MAPK, COX-2 and MUC5AC in nasal mucosa induced by histamine or blocked by selective inhibitors of p38MAPK and COX-2 of different concentration gradient. RESULT: Weak expressions of p38MAPK. COX-2 and MUC5AC were detected in normal nasal mucosa in vitro. The protein expressions of p38MAPK. COX-2 and MUC5AC increased in nasal mucosa induced by histamine in a dose-dependent manner. The histamine induced protein expressions of COX-2 and MUC5AC were dose-dependently attenuated by selective inhibitor of COX-2, namely NS-398. No apparent influence of NS-398 on the expression of p38MAPK was observed. The histamine induced protein expressions of p38MAPK, C()X-2 and MUCbAC dose-dependently decreased after nasal mucosa was treated by selective inhibitor of p38MAPK, namely SB203580. And no significant change of MUC5AC protein expression induced by NS-398 or SB203580 was observed. CONCLUSION Our findings indicated that the histamine-induced increased expression of MUC5AC by activated p38MAPK/COX-2 may be a possible pathogenesis of mucus hypersecretion in AR.
Adult ; Female ; Humans ; Male ; Middle Aged ; Mucin 5AC ; metabolism ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Perennial ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism

ObjectiveTo explore the effect and mechanism of Qizhu prescription on liver lipid anabolism and oxidative stress in mice with non-alcoholic steatohepatitis （NASH） based on adenylate activated protein kinase （AMPK） signaling pathway. MethodA total of 60 male C57BL/6J mice were randomly divided into a normal group （n = 10） and a modeling group （n = 50）. The modeling group was fed by high-fat and high-cholesterol diet for 16 weeks to establish the NASH mice model and was randomly divided into model group， low-， medium， and high-dose groups of Qizhu prescription， and Yishanfu group， with 10 mice in each group. Qizhu prescription was administered intragastrically once a day at a dose of 4.75， 9.50， and 19.00 g·kg^-1 in each group and 228 mg·kg^-1 in Yishanfu group. The normal group and model group were given equal volumes of pure water for eight weeks. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglyceride （TG）， and glucose （GLU） levels were detected. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） and oil red O staining. Serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， free fatty acids （FFA）， reduced glutathione （GSH）， malondialdehyde （MDA）， catalase （CAT）， and superoxide dismutase （SOD） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of acetyl-CoA carboxylase （ACC）， carnitine palmitoyl transferase 1A（CPT1A）， and mitochondrial uncoupling protein 2 （UCP2） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of AMPK， p-AMPK， ACC， CPT1A， and UCP2 in liver tissue were detected by Western blot. ResultCompared with the normal group， the liver steatosis of the model group was obvious， with multiple inflammatory clusters and large amounts of intracellular lipid deposition. The activity of serum AST， ALT， as well as levels of IL-6， IL-1β， TNF-α， FFA， and MDA were significantly increased， the activity of CAT and SOD was significantly decreased， and the mRNA and protein expressions of ACC were significantly increased. The mRNA and protein expressions of CPT1 and UCP2 were significantly decreased， and the protein expression of p-AMPK was significantly decreased （P<0.01）. Compared with the model group， the degree of liver steatosis in the Qizhu prescription and Yishanfu groups was reduced， the activity of AST and ALT， as well as the levels of IL-6， IL-1β， TNF-α， FFA， and MDA was significantly decreased， and the activity of CAT and SOD was significantly increased （P<0.01）. The mRNA and protein expressions of ACC in liver tissue of mice in medium- and high-dose groups of Qizhu prescription were significantly decreased， while the mRNA and protein expressions of CPT1A and UCP2， as well as p-AMPK protein were significantly increased （P<0.01）. ConclusionQizhu prescription can improve liver lipid metabolism， reduce oxidative stress， and promote liver cell repair in NASH mice by activating the AMPK signaling pathway.

Anti neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a systemic disease characterized by small vessel wall inflammation and cellulose necrosis mediated by ANCA. Renal injury caused by AAV is called ANCA-associated glomerulonephritis (AAGN). The paper reported a case of AAV with renal damage combined with human immunodeficiency virus (HIV) infection. The patient was an elderly male with clinical manifestations of hematuria and uremia. Renal pathological examination showed AAV and renal injury. This case is the first report in China while reviewing the relevant literature, and it is still inconclusive whether this is an overlap of the two diseases or a specific pathological type of HIV-associated nephritis. We believe that AAV has the potential to occur in HIV-infected patients, so clinicians should not ignore the phenomenon of ANCA positivity in HIV-infected patients, and the follow-up of such patients needs to be enhanced. Clinical and renal pathological examinations are the main methods to diagnose HIV infection with AAV. At the same time, there are no clear guideline guidelines on how to administer immunosuppressive therapy for such patients who have immunodeficiency and are at higher risk of opportunistic infections, and in whom to make the best possible outcomes.

Objective To investigate the popularization of cardiopulmonary resuscitation(CPR)knowledge and science popularization needs among urban and rural residents in Tonghai County,Yuxi City,Yunnan Province,so as to explore the establishment of an efficient and appropriate science popularization model.Methods A total of 300 residents aged 15-60 years old were selected from Tonghai County,Yuxi City,Yunnan Province using stratified and simple random sampling methods.A self-designed questionnaire was used to conduct an anonymous questionnaire survey.Results Only 20.3%of Tonghai County residents master CPR skills,and 26.2%of Tonghai County residents have never heard of CPR.There is a statistically significant difference in the awareness rate of CPR between rural residents and non-rural residents(P<0.01).There are differences in residents'age and CPR awareness(P<0.01),the age and CPR are inversely proportional.The residents have a higher willingness to perform chest compressions and mouth-to-mouth resuscitation on strangers,66.2%and 68.6%respectively.63.79%of residents have never attended relevant training.But 92.76%of the people said they were willing to participate in the relevant training when they learned the training news.Conclusion Residents in Tonghai County generally lack knowledge of CPR first aid,but the demand for first aid knowledge of residential CPR is high and the attitude towards rescue is positive.It is recommended that relevant departments increase CPR science popularization and training efforts,and popularize CPR into villages.

Objective To investigate the efficacy and the collective brain responses of acupuncture for post-stroke limb numbness.Methods A total of 24 patients with post-stroke limb numbness and 23 matched healthy participants were recruited.Both groups received coordinated acupuncture treatment to regulate their physical and mental state,three times a week for 4 weeks.Changes in limb numbness assessed by the visual analog scale(VAS)were observed before and after acupuncture.Functional magnetic resonance imaging(fMRI)scans were conducted on the participants during the scanning process with acupuncture intervention.Blood oxygen level-dependent(BOLD)data were collected in three states:resting state,acupuncture task state,and needle retention state.Data processing was performed using software such as fMRIPrep and brainIAK.Intersubject correlation(ISC)analysis was conducted to compare the ISC values of different brain regions between the two groups under different conditions.Results Acupuncture treatment significantly reduced the VAS scores of limb numbness.No significant changes in ISC values in both groups during resting state.Under acupuncture conditions,the patient group exhibited significantly increased ISC values in the left precentral gyrus,left paracentral lobule,left postcentral gyrus,left insula,left anterior cingulate gyrus,right middle frontal gyruss and right anterior cingulate gyrus.Under the needle retention condition,a slight negative activation was observed in the bilateral precentral gyrus of the control group.In the patient group,the ISC values of the left superior frontal gyrus,left precentral gyrus,left paracentral lobule,left precuneus,left postcentral gyrus,left insula,left anterior cingulate gyrus,left thalamus,right superior frontal gyrus,right middle frontal gyrus,right precentral gyrus,and right anterior cingulate gyrus showed a significant increase compared to the resting state.Conclusion Acupuncture can improve post-stroke limb numbness symptoms and induce a specific pattern of collective brain activation in patients.This activation involves the precentral gyrus,postcentral gyrus,thalamus,insula,frontal lobe and cingulate gyrus.Acupuncture may enhance the processing of sensory information by activating the somatosensory-motor network and the cortical-thalamic-cortical loop.It may also modulate the central executive network and the descending pain control pathway to promote the relief of pain symptoms.

Objective:To optimize the different salt preparation processes of salt-processed Psoraleae Fructus and compare the differences among different salt products.Methods:Ultra-high performance liquid chromatography (UPLC) characteristic chromatogram of Psoraleae Fructus was established. By using the comprehensive scoring method, the total content of psoralen and isopsoralen and the peak area of the characteristic chromatogram were used as the evaluation index to optimize the four different processing technologies, including "stir-frying with salt-water", "steaming with salt-water", "spraying with salt-water" and "microwaving with salt-water". Meanwhile, entropy weight TOPSIS method, clustering analysis (HCA), principal component analysis (PCA) and other chemical pattern recognition methods were used to compare the quality difference of different salt-processed Psoraleae Fructus.Results:The optimized "stir-frying with salt-water" process of salt-processed Psoralea Fructus was 170 ℃ for 13 min, "steaming with salt-water" process for 1 h, "spraying with salt-water" process for 110 ℃ for 13 min and "microwaving with salt-water" process for 105 s microwave heating. TOPSIS comprehensive evaluation results of entropy weight showed that the quality of different salt products of Psoraleae Fructus ranked as product of stir-frying with salt-water > product of stir-frying with green salt-water > product of spraying with salt-water > product of microwaving with salt-water > product of steaming with salt-water; HCA results showed that different salt products of Psoraleae Fructus could be polymerized into two categories, between which product of stir-frying with salt-water and product of stir-frying with green salt-water were polymerized into one category; product of spraying with salt-water, product of microwaving with salt-water and product of steaming with salt-water were another category; the results of PCA showed that different salt products of Psoraleae Fructus could be clustered into 4 categories, among which product of stir-frying with salt-water, product of stir-frying with green salt-water and product of spraying with salt-water were clustered into the same category respectively, and product of microwaving with salt-water and product of steaming with salt-water were clustered into the same category.Conclusion:The chemical composition of Psoraleae Fructus processed by different salting methods is different. The results of this study can provide reference for processing optimization of salt-processed Psoraleae Fructus and identification of different salt products.

OBJECTIVE To estimate the quality markers of antioxidant activity for standard decoction of Schisandrae Chinensis Fructus.METHODS 15 batches of Schisandrae Chinensis Fructus standard decoctions were subjected to quality evaluation by ultra high-performance liquid chromatography(UPLC)based on single-marker(QAMS)method,before being summarized by chemometrics analysis.The antioxidant abilities of 15 batches of samples were determined by DPPH and ABTS methods,while gray correlation analy-sis(GRA)and the partial least squares regression(PLSR)methods were subsequently applied to investigating the relationship between the contents of 8 components and the antioxidant activity.Ultimately,molecule docking was utilized to explore the binding properties between candidate quality markers and the core targets of anti-oxidation,with the experimental verification being executed on the indi-vidual compound by in vitro anti-oxidation.RESULTS There was no remarkable difference between the results of QAMS and external standard method(ESM),with P valued greater than 0.05.And it was speculated that protocatechuic acid,gomisin A,schizantherin B and schisandrin B were the constituents of quality difference.Moreover,the 4 quality variation components were reckoned to be the al-ternative markers on antioxidant according to the results of GRA and PLSR.The molecule docking result also showed that 4 candidate quality markers presented good binding affinity with the antioxidant core targets.The antioxidant capacity was presumably originated from the collaborated effects by multi-components in the standard decoction of Schisandrae Chinensis Fructus.In the interim,protocate-chuic acid exhibited noteworthy antioxidant efficacy with dosage-depended manner in the results of single-compound verification,which was best conformed to the characteristics of quality markers and supposed to be the antioxidant quality marker for Schisandrae Chinensis Fructus standard decoction.CONCLUSION This research predicts the potential antioxidant substances on the basis of content deter-mination by UPLC and in vitro antioxidant assay,but also provides rational foundation for quality assessment on other preparations of Schisandrae Chinensis Fructus.