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 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 explore the value of convalescent somatosensory evoked potentials (SEPs) in formulating a prognosis for children with severe disorders of consciousness (DOC) caused by brain trauma, infection or hypoxia.Methods:This was a retrospective cohort study of 286 children with DOC children treated between 2013 and 2021. They were divided into a trauma group ( n=103), an intracranial infection group ( n=101), a hypoxia group ( n=42) and an other-causes group ( n=40). Their consciousness status and functional recovery were obtained in follow-up appointments, and their functional condition 1 year after discharge was assessed using the modified Glasgow Outcome scale (GOS). Results:During 8-year follow-up, 16 had died, with 4 deaths within 1 year. Among the 191 cases followed up to 1 year, children with a bilateral N20 SEP had significantly better functional outcomes than those with unilateral or bilateral N20 absence. For the trauma group, the presence of a bilateral N20 signal was a strong indicator of good functional outcome at the 1-year follow-up, with a specificity of 90.9%, sensitivity of 55.6%, positive predictive value (PPV) of 92.6%, negative predictive value (NPV) of 50% and a positive likelihood rate (PLR) of 6.111. However, for the intracranial infection group, the presence of N20 had a low specificity for predicting good outcomes, though the absence of an N20 potential predicted poor functional outcome at 1 year with a specificity of 82.4%, sensitivity of 62.1%, PPV of 75%, and PLR of 3.517. For the hypoxic group, bilateral N20 could not predict a good prognosis, though its absence meant a poor outcome, with a specificity of 87.5%, sensitivity of 63.6%, PPV of 93.3%, and PLR of 5.818.Conclusion:SEPs during the recovery period can help to formulate a prognosis for children with severe DOC. Traumatic brain injury and the presence of bilateral N20 potentials can be used as a good prognostic indicator. For intracranial infection and hypoxic-ischemic brain injury, the absence of an N20 potential indicates a poor prognosis.

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO₂/FiO₂), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO₂/FiO₂, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.
Humans ; Retrospective Studies ; Alcoholism ; Prognosis ; Respiratory Distress Syndrome ; Pneumonia ; Sepsis ; Intensive Care Units ; Procalcitonin ; Fibrinogen ; ROC Curve