Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To evaluate the role of transthoracic echocardiography ( T T E ) and transesophageal echocardiography( T EE) in the process of transapical mitral valve repair using a novel edge‐to‐edge device( ValveClamp) and this device′s efficacy and safety in a preliminary clinical trial . Methods Six patients with moderate to severe or severe degenerative mitral regurgitation ( DM R) confirmed by T T E and T EE were enrolled . T T E was performed pre and post procedure as well as 30 days post procedures . Related cardiac structure and hemodynamic parameters ,including mitral regurgitation area ( MRA‐max ) , vena contracta width ( VCW ) ,mitral valve effective orifice area ( M VEOA ) ,left ventricular end diastolic diameter ( LVEDD ) , left ventricular end systolic diameter ( LVESD ) , left ventricular ejection fraction ( LVEF) ,max and mean mitral valve pressure gradient ( M VPG‐max and M VPG‐mean) were recorded and evaluated in a central core laboratory . Results All the procedures were successfully performed .M RA‐max , VCW and M VEOA decreased significantly post procedures ( all P ＜ 0 .000 ) , and they remained no significant changes within 30 days post procedures ( all P ＞ 0 .05 ) . M eanwhile ,M VPG‐max and M VPG‐mean slightly increased ( all P ＜0 .01 ) and left atrial anterior‐posterior dimension attenuated 30 days post procedures( P ＜0 .05) ,but all M VPG‐mean were lower than 5 mm Hg ( 1 mm Hg＝0 .133 kPa) . T here were no significant changes in other hemodynamic parameters ( all P ＞ 0 .05) . Conclusions T ransapical mitral valve repair using ValveClamp can be performed safely and a significant reduction in mitral regurgitation can be achieved in patients with DM R . T EE and T T E facilitate the patient selection for ValveClamp procedures as well as perioperative navigation and assessment .

PURPOSE: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. METHODS: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. RESULTS: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with cough-variant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. CONCLUSIONS: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591550
Age Distribution ; Asian Continental Ancestry Group ; Asthma ; Capsaicin ; China ; Cough ; Female ; Healthy Volunteers ; Humans ; Male ; Reflex ; Sex Distribution

The clinical presentation,chest image and electrocardiogram of 4 cases of premature complex-induced chronic cough admitted in the First Affiliated Hospital of Guangzhou Medical University from March 2008 to February 2009,were retrospectively analyzed.And other 6 cases of premature complex-induced chronic cough were retrieved for literature review.In total 10 patients,there were 3 males and 7 females aged 58(36-74) years,with a disease duration of 10.5 (3.0,264.0) months.The main clinical presentations were chronic dry cough with post-sternal thump and premature beats as shown by auscultation and 24 h-electrocardiogram examination.Cough was relieved after the premature beats were controlled with the treatment of arrhythmia drugs or radiofrequency ablation.Premature complex-induced cough is rare but it should be considered when the chief complaint of patients with premature beat is chronic cough.

Objective? To anaLyze the infLuencing factors of stress hypergLycemia in patients undergoing surgery for non-diabetic Standard Type A aortic dissection and to expLore the methods of its monitoring and management. Methods? TotaLLy 100 patients with non-diabetic Standard Type A aortic dissection admitted in the Department of Cardiac Surgery, Zhongshan HospitaL were retrospectiveLy incLuded. Their generaL information incLuding age, gender, body mass index (BMI), pain score, operation time and time of circuLatory arrest as weLL as morning fasting bLood-gLucose (FBG) before operation, before extracorporeaL circuLation, before and after circuLatory arrest, after rewarming, after machine haLt, at ICU admission and on 1 - 6 day postoperativeLy was coLLected. Univariate anaLysis and Logistic regression anaLysis were used to expLore the factors affecting the peak bLood-gLucose perioperativeLy. ResuLts? The area under the ROC curve for perioperative bLood-gLucose and overaLL adverse outcome was 0.646 (95%CI 0.528-0.763,P=0.021), and the comparativeLy good cutoff vaLue of perioperative peak bLood-gLucose for the disease was 14.35. The patients' bLood-gLucose started to rise after extracorporeaL circuLation, and the tendency to rise was more significant after rewarming. Their bLood-gLucose remained at a reLativeLy high LeveL at ICU admission. It tended to decrease since 24 h postoperativeLy, and it returned to normaL LeveLs at 6 d post operation. Univariate anaLysis showed that there was statisticaL difference in BMI, white bLood ceLL, C-reactive protein (CRP), time of extracorporeaL circuLation, Acute PhysioLogy and Chronic HeaLth EvaLuation Scoring System (APACHEⅡ) and whether emergency surgery received between the patients with ≥14.35 mmoL/L or ＜14.35mmoL/L bLood-gLucose perioperativeLy (P＜0.05). According to Logistic regression anaLysis, BMI, CRP and time of extracorporeaL circuLation were independent risk factors of stress hypergLycemia in patients undergoing surgery for non-diabetic Standard Type A aortic dissection (OR＞1). ConcLusions? Severe infLammatory response and high BMI preoperativeLy indicate that stress hypergLycemia may occur in patients undergoing surgery for non-diabetic Standard Type A aortic dissection during the perioperative period. Perioperative hypergLycemia can be reduced by reducing the time of extracorporeaL circuLation. MedicaL and nursing workers need to enhance gLycemic monitoring in the process of extracorporeaL circuLation, after rewarming and post operation and deveLop targeted gLycemic management protocoLs for the patients.

PURPOSE: Extensive data support the influence of the upper airway on lower airway inflammation and pathophysiology in allergic disease. However, few studies have focused on allergic inflammation in the nose after an isolated lower airway allergen challenge, a situation that can exist clinically when human subjects breathe primarily through the mouth, as occurs when nasally congested. This study used a mouse model to investigate whether upper airway inflammation and hyperresponsiveness were induced by an isolated lower airway allergen challenge. METHODS: BALB/c mice were sensitized by systemic intraperitoneal injection of ovalbumin/saline and challenged with intratracheal ovalbumin/saline. Inflammation in the nose and lungs was assessed by cytology and histology of nasal tissues and bronchoalveolar lavage fluid (BALF), while nasal airway resistance and response were measured over 3 days post-challenge. RESULTS: Intratracheal application of an allergen in anaesthetized mice resulted in exclusive deposition in the lower airway. Compared to control animals, ovalbumin-sensitized mice after challenge showed bronchial hyperreactivity and increased IL-5 in the serum BALF, as well as eosinophil infiltration in the lungs. However, nasal histology of the ovalbumin-sensitized mice showed no increase in eosinophil infiltration. The nasal lavage fluid revealed no increase in eosinophils or IL-5, and the nasal airway resistance did not increase after challenge either. CONCLUSIONS: In a mouse allergy model, exclusive allergen challenge of the lower airway can elicit a pulmonary and systemic allergic response, but does not induce upper airway inflammatory or physiological responses.
Airway Resistance ; Animals ; Asthma* ; Bronchial Hyperreactivity ; Bronchoalveolar Lavage Fluid ; Eosinophils ; Estrogens, Conjugated (USP) ; Humans ; Hypersensitivity ; Inflammation* ; Injections, Intraperitoneal ; Interleukin-5 ; Lung ; Mice ; Mouth ; Nasal Lavage Fluid ; Nose* ; Rhinitis

Objectiev To explore the use of different nebulizer to establish mice model that have airway eosinophilic inflam -mation without airway hyperresponsiveness .Methods Female BALB/c mice were obtained and divided randomly into 3 groups:eo-sinophilic airway inflammation group ( experimental group ) , asthma group, and control group .Mice were immunized with ovalbumin ( OVA) .The experiment group and asthma group were challenged with an aerosol of 1% w/v OVA using a PARI TIA and PARI LC STAR nebulizer on day 28, 29, 30, respectively.The control mice were received saline sensitization and challenge .Airway respon-siveness was measured .Cell different counts in bronchial alveolus lavage fluid ( BALF) were performed and a pathologist performed histopathological evaluation of the trachea and lung .Results Airway responsiveness in the experimental group was not significantly different compared with the normal saline ( NS) group but was significantly different compared with the asthma group .Eosinophils in BALF were increased significantly in experimental group compared with the NS group , and significant difference was observed between experimental group and asthma group .The intensity of airway inflammation in experimental group was milder than that in the asthma model .Conclusions We established an eosinophilic bronchitis mice model without hyperresponsiveness successfully .Our model es-tablished a foundation for the further research in airway hyperresponsiveness .

Cough is one of the most common symptoms of many respiratory diseases; the characteristics of intensity and frequency of cough sound offer important clinical messages. When using these messages, we have need to differentiate the cough sound from the other sounds such as speech voice, throat clearing sound and nose clearing sound. In this paper, based on Empirical Mode Decomposition (EMD) and Hidden Markov Model (HMM), we proposed a novel method to analyze and detect cough sound. Employing the property of adaptive dyadic filter banks of EMD, we gained the mean energy distribution in the frequency domain of the signals in order to analyze the statistical characteristics of cough sound and of other sounds not accompanied by cough, and then we found the optimal characteristics for the recognition using HMM. The experiments on clinical date showed that this optimal characteristic method effectively improved the detective rate of cough sound.
Cough ; diagnosis ; physiopathology ; Diagnosis, Computer-Assisted ; methods ; Humans ; Markov Chains ; Monitoring, Physiologic ; methods ; Pattern Recognition, Automated ; methods ; Sound ; Sound Spectrography ; methods

Objective To investigate the severity of cough in patients with different etiology of chronic cough and its related factors. Methods One hundred and fifty patients with chronic cough were recruited. The diagnosis of the patients was as follows: 24 cases with post nasal drip syndrome (PNDs), 26 cough variant asthma (CVA), 20 gastroesophageal reflux-induced cough (GERC), 31 eosinophilic bronchitis (EB), 30 atopic cough (AC) and 19 cough post infection (CPI). The severity of cough at daytime and night-time were scored by the doctor and the patient at the first visit. The correlation between cough score and age, gender and course duration of patients was analyzed. Results There was no significantly difference of cough score at daytime among different groups. Cough score at night in CVA group was significantly higher than that of other five groups (all P <0.01). Regression analysis showed that cough score at daytime was significantly correlated with age of patients (P < 0.05), while cough score at night was correlated significantly with gender (P < 0.01). Conclusion Cough severity at daytime in different etiology of chronic cough is similar, while that at night in patient with CVA is higher than that with other etiology.

Objective:To find related polypeptides which could bind interleukin (IL) 5 with high affinity.Methods:The recombinant human IL 5 was biotinylated with NSH LC Biotin,then biotinylated IL 5 was used to react with random peptide library displaying 7 amino acids fused on protein III of M13 Phage for three rounds biopanning.The selected clones were assayed by sandwich enzyme linked immunosorbent assay(ELISA)and competition ELISA.The positive clones with high affinity were used for automated sequencing with dye labeled dideoxynucleotides,and the amino acid sequence of polypeptide displayed on phage was deduced.Results:The enrichment was shown by ELISA after 3 rounds of biopanning.9 positive clones could bind to IL 5 with high affinity.Sequencing of the genes encoding these peptides on 9 positive clones showed some conserved epitope information such as SX 1 2 AS,ALAS.Conclusion:Potential polypeptides binding IL 5 with high affinity could be selected from phage display peptide library,SX 1 2 AS may be the motifs recognized by IL 5.