Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation / 药物分析学报

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.

Autologous blood transfusion during heart valve replacement surgery: a retrospective study / 中国输血杂志

【Objective】 To retrospectively analyze the indexes of autologous blood transfusion during heart valve replacement, in order to provide reference for allogeneic blood transfusion during heart valve replacement surgery under direct vision. 【Methods】 The data of 180 patients who underwent heart valve replacement in our hospital from January 2020 to December 2021 were analyzed retrospectively. The patients were divided into allogeneic and non-allogeneic blood transfusion group based on whether allogeneic blood was transfused during the operation, and the general data and 24 hours pre- and post-operative clinical examination indexes were compared. 【Results】 Multivariate logistic regression analysis showed that age (OR=1.110, 95% CI: 1.058-1.165, P<0.05) and intraoperative cardiopulmonary bypass time (OR=1.062, 95% CI: 1.038-1.086, P<0.05) were risk factors for allogeneic blood transfusion, and preoperative Hb content (OR=0.910, 95%CI: 0.868-0.953, P<0.05) was a protective factor. The RBC count(4.16±0.73 vs 4.52±0.71)×1012/L and Hb(120.94±17.97 vs 136.57±19.33) g/L at 24 hours preoperative in the allogeneic transfusion group were lower than those in the non-allogeneic transfusion group, and the RBC(3.51±0.53 vs 4.13±0.78)×1012/L, Hb(114.15±11.68 vs 124.79±14.96)g/L and platelet count(124.28±32.11 vs 148.29±26.62)×109/L at 24 hours postoperative were significantly lower than those in the non-allogeneic transfusion group (P<0.05). 【Conclusion】 Age and intraoperative cardiopulmonary bypass time are the risk factors for autologous and allogeneic blood transfusion during heart valve replacement under direct vision, and the preoperative Hb content is a protective factor. It is necessary to evaluate the symptomatic treatment of patients before operation and reduce allogeneic blood transfusion.

Characteristics of Early Cardiac Involvement in 45 Patients With Fabry Disease Monitored by Ultrasonic Cardiogram / 中山大学学报(医学科学版)

ObjectiveTo evaluate the changes in cardiac structure and ventricular function in patients with Anderson-Fabry Disease （AFD） by two-dimensional speckle tracking echocardiography （2D-STE） and to explore the characteristics of their early cardiac involvement. MethodsAll 45 patients diagnosed with AFD in this observational study underwent routine ultrasonic cardiogram （UCG） examination and 2D-STE. The patients were divided into 2 groups based on UCG measurements： with left ventricular hypertrophy （interventricular septum or posterior left ventricular wall thickness ≥12 mm） and without left ventricular hypertrophy. TomTec software was used to analyze the echocardiographic images， then the baseline data， UCG routine parameters and myocardial strain of the two groups were compared. ResultsThe study included 27 males （60.0%） and 18 females （40.0%）， with an average age of （32.33±16.11）， 17 cases （37.78%） with left ventricular hypertrophy and 28 cases （62.22%） without left ventricular hypertrophy. All patients had normal left ventricular ejection fraction （LVEF） （> 50%）. Compared with those without left ventricular hypertrophy， patients with left ventricular hypertrophy had significantly more target organ involvement， significantly higher E/A and average E/E' ratios （P < 0.05）. No statistical difference was found in global and segmental longitudinal strain （LS）， circumferential strain （CS） and radial strain （RS） of the endocardium and myocardium between the two groups （all P > 0.05）. There were lower absolute values of global and segmental LS and CS in the myocardium than in the endocardium （all P < 0.05）， and higher absolute values of LS and RS in the mid segment than in the basal and apical segments （all P < 0.05）. ConclusionsThere is no significant association between early systolic dysfunction and left ventricular wall thickness. 2D-STE strain can be used to detect AFD in the early stage. Ventricular wall myocardium exhibits more serious involvement than endocardium and mid segment was less involved than the apical and basal segments.

Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol:Nested Case-Control and Case-Time-Control Studies

Purpose@#Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. @*Materials and Methods@#We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens–Johnson syndrome (SJS), using the claims database of South Korea, 2010–2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. @*Results@#We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71–3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09–3.47). @*Conclusion@#In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

Effects of electroacupuncture at "Siguan" points on the expression of colonic 5-hydroxytryptamine and fecal short-chain fatty acids in rats with post-stroke depression / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD.@*METHODS@#Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg-1•d-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg-1•d-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry.@*RESULTS@#After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004).@*CONCLUSION@#Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.

Effects of COVID-19 and Influenza Vaccination on Rheumatic Diseases:Results From a Survey of PatientReported Outcomes After Vaccination

Background@#This study aimed to compare the occurrence of adverse events (AEs) and disease flares after vaccination against coronavirus disease 2019 (COVID-19) and influenza in patients with autoimmune rheumatic diseases (ARDs). @*Methods@#Between November 2021 and March 2022, a survey was conducted among patients with ARD who received COVID-19 and influenza vaccinations. The questionnaire included 11 mandatory and closed-ended questions, and the following items were collected: medical history, immunization history, type of vaccine, patient-reported AEs, flare-up of the underlying disease after vaccination, and a confirmed diagnosis of COVID-19 or influenza. We compared the occurrence of vaccine-related adverse reactions to the COVID-19 and influenza vaccines based on the survey results. Multivariate logistic regression analysis was used to identify the factors affecting AEs or disease flares and to compare the post-vaccine response to mixed and matched vaccines. @*Results@#We analyzed 601 adults with ARD who received the COVID-19 vaccine, with a mean age of 49.6 years (80.5% female). A total of 255 participants (42.4%) received a complete course of primary vaccination, 342 (56.9%) completed the booster dose, and 132 (38.6%) received a mixed vaccine. The frequencies of AEs (188 [52.2%] vs. 21 [5.8%]; P< 0.001) and disease flares (58 [16.2%] vs. 5 [1.4%]; P < 0.001) after COVID-19 vaccination were significantly higher than those after influenza vaccination. In the risk factor analysis, previous allergic reaction to other vaccines (odds ratio, 1.95; confidence interval, 1.07–3.70; P = 0.034) was the only factor associated with the occurrence of AEs. There was no difference in the post-vaccine responses between the mixed and matched vaccines. @*Results@#We analyzed 601 adults with ARD who received the COVID-19 vaccine, with a mean age of 49.6 years (80.5% female). A total of 255 participants (42.4%) received a complete course of primary vaccination, 342 (56.9%) completed the booster dose, and 132 (38.6%) received a mixed vaccine. The frequencies of AEs (188 [52.2%] vs. 21 [5.8%]; P < 0.001) and disease flares (58 [16.2%] vs. 5 [1.4%]; P < 0.001) after COVID-19 vaccination were significantly higher than those after influenza vaccination. In the risk factor analysis, previous allergic reaction to other vaccines (odds ratio, 1.95; confidence interval, 1.07–3.70; P = 0.034) was the only factor associated with the occurrence of AEs. There was no difference in the post-vaccine responses between the mixed and matched vaccines. @*Conclusion@#The results of the survey of patients with ARD revealed that patient-reported AEs and underlying disease flares after receiving the COVID-19 vaccine were significantly higher than those after the influenza vaccine.

Treatment with biological products for chronic urticaria

Chronic urticaria is characterized by repeatedly occurring itchy wheals and/or angioedema for at least six weeks. The prevalence of chronic urticaria is increasing globally, with variations observed among different regions. Chronic urticaria has a long duration and may recur over time. Effective and tolerable treatment for such patients is crucial due to unpredictable, recurrent, and disabling symptoms, as well as the significant impact on quality of life.Current Concepts: Recent guidelines recommend the regular use of non-sedative second generation antihistamines as the first line of treatment for chronic urticaria. For patients whose urticarial symptoms persist or worsen with the approved dose of antihistamines, the guideline recommends the second line of treatment, which involves either increasing the dosage of the initial antihistamine or combining it with three other kinds of antihistamines. However, almost half of patients with chronic urticaria are refractory to antihistamines. Recently, treatment modulating immunoglobulin E (IgE) levels and activities was found to provide an efficient therapeutic approach. Omalizumab, the only approved anti-IgE treatment to date for patients with chronic urticaria, has demonstrated strong evidence of both efficacy and safety. Recent international guidelines recommend omalizumab as the first choice of treatment for antihistamine-refractory chronic spontaneous urticaria.Discussion and Conclusion: As omalizumab is not a curative and disease-modifying agent, there is a subpopulation of patients with chronic spontaneous urticaria who partly or have never responded to omalizumab. To address this, ongoing research is exploring the therapeutic potential of other biological products that target various aspects, such as type 2 inflammation, complement system, and the c-kit pathway.

A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Efficacy of combined treatment with mechanical circulation support devices and immunomodulation therapy for patients with fulminant myocarditis / 中华心血管病杂志

Objective: To summarize the efficacy of combined treatment strategy of mechanical circulation support devices and immunomodulation therapy for patients with fulminant myocarditis. Method: We retrospectively analyzed the clinical data and outcomes of 37 fulminant myocarditis patients complicating cardiogenic shock, who were hospitalized from October 2017 to December 2019 in our department. Patients received guideline therapy according to "Chinese expert consensus statement on clinical diagnosis and treatment of fulminant myocarditis in adults"issued by Chinese Society of Cardiology of Chinese Medical Association. Patients were divided into IABP group (n=19), ECMO group (n=5) and IABP+ECMO group (n=13) according to different mechanical circulation support regimen. The treatment effectiveness among various groups were compared. The major endpoint was in-hospital mortality. The duration and outcome of mechanical circulation support were also analyzed. Furthermore, relationships between baseline data, proportion of different treatments (including medicine treatment, temporary pacemaker and continuous renal replacement treatment, immunomodulation therapy) and clinical outcome were analyzed. Results: The age of the 37 patients in the cohort was (37.4±17.0) years, and there were 22 male among them. Immunomodulation therapy included glucocorticoid (methylprednisolone) and intravenous immunoglobin. At admission, blood pressure was (70.21±17.37)mmHg(1 mmHg=0.133 kPa),heart rate was(100±30)beat/minutes,there were 10 cases of Ⅲ° atrioventricular block and all received temporary pacemaker implantation, 12 cases of ventricular tachycardia and fibrillation,1 patient received temporary pacemaker implantation due to electronic storm, peak cardiac troponin I level was (18.61±9.55)μg/L, peak B type natriuretic peptide level was 1 670(518,3 410)ng/L,left ventricular ejection fraction (LVEF) was(32.3±10.4)%. Thirty-four out of the 37 patients survived and 3 patients died. Hospital duration was (22.7±8.2)days, LVEF was (50.1±10.5)% at discharge. Lactic acid level was significantly higher in IABP+ECMO group than in IABP group and ECMO group(P<0.001 or =0.005),LVEF was significantly lower in IABP+ECMO group than in IABP group(P=0.004),the proportion of ventilator usage was higher in IABO+ECMO group than in IABP group (P<0.05). Survival rate was similar among the three groups. Conclusion: Comprehensive treatment regimen with combined mechanical circulation support and immunomodulation therapy as the core strategies is effective in the treatment of fulminant myocarditis complicated with cardiogenic shock.

Efficacy and safety of percutaneous closure of ventricular septal rupture after acute myocardial infarction: a clinical study of 69 cases / 中华心血管病杂志

Objective: To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI) and the risk factors of all-cause mortality at 30 days after operation. Methods: This is a retrospective case series study. A total of 69 patients with post-AMI VSR, underwent percutaneous closure of VSR from October 2013 to May 2020 in Department of Cardiology of Henan Provincial People's Hospital and Department of Cardiology of Central China Fuwai Hospital, were included. Patients were divided into survival group (53 cases) and non-survival group (16 cases) according to the status at 30 days after operation. Clinical data were collected and analyzed during hospitalization. Telephone follow-up was performed 30 days after operation. The primary safety endpoint was occlusion failure and all-cause mortality at 30 days post operation. The secondary safety endpoint was the operation related or non-operation related complications. Efficacy endpoint included NYHA classification of cardiac function, index measured by right heart catheterization and echocardiography. Multivariate logistic regression was performed to analyze the risk factors of all-cause mortality at 30 days after operation. Results: A total of 69 patients, aged 67 (64, 71) years, including 42 women (60.9%), were enrolled in this study. All-cause death occurred in 16 patients (23.2%), including 13 in-hospital death and 3 death during follow-up. There were 4 cases of closure failure (5.8%). Among the 65 patients with successful closure, 12 (18.5%) experienced operation-related complications, among which 8 (12.3%) experienced valve injury. The mortality was significantly higher in patients with operation-related complications than that in patients without operation-related complications (41.7% (5/12) vs. 13.2% (7/53), P = 0.022). One case received percutaneous closure of VSR and PCI, this patient experienced new-onset AMI immediately post procedure and died thereafter (1.5%). One case (1.5%) developed multiple organ failure and 2 cases (3.1%) developed gastrointestinal bleeding post operation. All of the 65 patients with successful occlusion completed postoperative echocardiography, 56 patients completed cardiac function assessment at discharge, and 53 patients who survived up to 30 days post discharge completed clinical follow up by telephone. The NYHA cardiac function at discharge and 30 days after operation were significantly improved as compared to that before operation (P<0.001), the ratio of NYHA Ⅰ and Ⅱ patients was significantly higher post operation at these two time points as compared to baseline level (76.8% (43/56) vs. 23.1% (15/65), P<0.001, 77.4% (41/53) vs. 23.1% (15/65), P<0.001). The pulmonary circulation/systemic circulation blood flow ratio (Qp/Qs), pulmonary artery systolic pressure (PASP) and left ventricular end-diastolic diameter (LVDd) were decreased, aortic systolic pressure (ASP) and left ventricular ejection fraction (LVEF) were increased post operation (P<0.05). Multivariate logistic regression analysis showed that WBC>9.8×109/L (OR=20.94, 95%CI 1.21-362.93, P=0.037) and NT-ProBNP>6 000 ng/L (OR=869.11, 95%CI 2.93-258 058.34, P=0.020) were the independent risk factors of mortality at 30 days. Conclusions: Percutaneous closure in VSR after AMI is safe and effective. The increase of WBC and NT-ProBNP are the independent risk factors of all-cause mortality at 30 days after operation.

Application of sliding osteotomy in total knee arthroplasty for patients with extra-articular femoral deformity / 中国骨伤

OBJECTIVE@#In order to observe the clinical effects of sliding osteotomy for patients with severe knee osteoarthritis and varus knee due to complex femoral extra-articular deformity to achieve the medial and lateral soft tissue balancing during total knee arthroplasty.@*METHODS@#From June 2014 to January 2018, a total of 22 patients with severe knee osteoarthritis and complex extra-articular malformation of femurs were treated with total knee arthroplasty. There were 5 males and 17 females in this group, aged 48 to 76 years old, with an average age of (61.3±13.8) years old. All the patients had varus deformities caused by extra-articular deformities of femur. Hip-knee-ankle(HKA) angle was(158.8±9.7) ° before operation, and the average Knee Society Score (KSS) clinical score was 32.6±6.1;KSS function score was 35.8 ±9.6;the average Hospital for Special Surgical (HSS) score was 39.7±4.6;the average range of motion before operation was (80.6±10.7) °. The mechanical alignment method was used in joint replacement. The flexion space was balanced first. The coronal plane vertical sliding osteotomy was performed on the medial femoral condyle for the imbalance of coronal plane. The sliding distance of the osteotomy block was determined by straightening the gap between the inner and outer sides of the space until the space was balanced. After the separated segments were fixed with several screws, the prosthesis was installed as usual.@*RESULTS@#The wounds of all patients healed in the first stage, and no wound complications occurred. All the 22 patients were followed up, and the duration ranged from 18 months to 3 years with an average of (28.2±10.1) months. X-ray showed that the fracture line disappeared for 2 to 5(3.5±1.5) months without nonunion. HKA angle measured at the latest follow up was (178.8±0.7) °, which wassignificantly different from that before operation. The HSS score was 91.3 ±6.0;KSS clinical score 93.7±3.5;KSS functional score 81.2±6.5;and the average range of motion of knee joint was(121.7±11.6) °, which was statistically significant compared with that before operation.@*CONCLUSION@#For severe knee osteoarthritis patients with complex femoral extra-articular deformity, sliding osteotomy is performed. For severe varus deformity, downward sliding the medial femoral condyle is performed. The operation is relatively simple and the damage is small. It is easy to achieve the balance of internal and external soft tissue in flexion extension space. The short-term clinical effect is satisfactory.

Risk assessment and screening of common malignant tumors among female urban residents in Deyang / 公共卫生与预防医学

Objective To analyze the screening results and risk assessment of common malignant tumors among female residents in Deyang from 2017 to 2019, so as to provide basis for cancer prevention and control. Methods Women who underwent physical examinations and completed the survey of common malignant tumors related risk factors from 2017 to 2019 were selected. The high risk rate, screening rate and detection rate of common malignant tumor among female urban residents in Deyang were analyzed. Results From 2017 to 2019, a total of 49,871 female urban residents completed the survey of common malignant tumor related risk factors. The risk rates of breast cancer, lung cancer, cervical cancer and colorectal cancer were 13.24%, 7.65%, 12.92% and 5.53%, respectively. Among all the age groups, women at the age of 50~59 years old were at the highest risk of breast cancer, lung cancer, cervical cancer, colorectal cancer; The screening rates of breast cancer, lung cancer, cervical cancer and colorectal cancer were 24.68%, 11.72%, 34.62% and 14.15%, respectively; The screening rates of breast cancer, lung cancer, cervical cancer and colorectal cancer among women with different educational levels showed significant difference (P<0.05). The screen rates of breast cancer, lung cancer, cervical cancer and colorectal cancer among high risk groups were 24.68%, 11.75%, 26.56% and 14.35%, respectively; The detection rates of breast cancer, lung cancer, cervical cancer and colorectal cancer among the screening groups were 9.33%, 2.68%, 9.82%, and 2.02%, respectively (P<0.05). Conclusion Female residents in Deyang from 2017 to 2019 have high risk and detection rates of breast cancer and cervical cancer, so active screening of malignant tumors among urban female residents can effectively improve the residents' quality of life, and is of vital importance for the early diagnosis and treatment of malignant tumors.

Discovery and functional characterization of flavone O-glycosyltransferases in Scutellaria baicalensis / 药学学报

Huang-Qin is a traditional Chinese medicine with antiviral, antioxidant, and anti-inflammatory activities. Its major bioactive compounds are diverse flavone O-glucuronides and glucosides. Although three flavonoid O-glycosyltransferases have been identified from S. baicalensis, this information is not sufficient to elucidate the structural diversity of flavonoid glycosides. In this study, nine glycosyltransferase candidate genes were discovered from S. baicalensis by BLAST analysis and their functions were characterized after heterologous expression. Three new flavone O-glycosyltransferases were able to catalyze the formation of major compounds in S. baicalensis, including baicalin and wogonoside. These enzymes could also utilize exogenous flavones as sugar acceptors. This work further elucidates biosynthetic pathways for Scutellaria flavonoid O-glycosides.

Role and mechanism of hierarchical microchanneled bone scaffolds in promoting osteogenesis and angiogenesis / 中国组织工程研究

BACKGROUND: How to recruit endogenous seed cells to promote osteogenesis, provide appropriate bone regeneration microenvironment for cells and ensure the vascularization process of new bone are the difficulties of bone tissue engineering research. OBJECTIVE: To review the osteogenesis and vasculogenesis from the aspects of hierarchical microchanneled bone scaffold. METHODS: The first author searched relevant literature on the promoting effect of hierarchical microchanneled bone scaffold on osteogenesis and angiogenesis from China National Knowledge Infrastructure, Wanfang, PubMed and Web of Science databases from 1950 to 2020. The key words were “hierarchical microchanneled scaffolds, osteogenesis, and angiogenesis” in Chinese and English. Finally, a total of 52 articles meeting the inclusion criteria were selected. RESULTS AND CONCLUSION: Hierarchical microchanneled bone scaffold has a good role in promoting osteogenesis and vascularization, and has a good application prospect in bone tissue engineering. At present, hierarchical microchanneled bone scaffold is mature in the theory of bone tissue engineering. In vitro experiments have confirmed that the hierarchical microchanneled bone scaffold can promote the adhesion and differentiation of mesenchymal stem cells into osteoblasts, but the osteogenic effect in vivo is still poor, and it is still possible to further improve the osteogenic effect. In the future, we should focus on the construction of hierarchical microchanneled bone scaffold complexes, such as chemokines or cytokines, which can further improve the osteogenic efficiency in vivo.

Simultaneous determination of 35 constituents and elucidation of effective constituents in a multi-herb Chinese medicine formula Xiaoer-Feire-Kechuan / 药物分析学报

Xiaoer-Feire-Kechuan (XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the anti-inflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were estab-lished and validated to quantify 35 analytes (covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A (8-10),and baicalin (15) (total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities (inhibitory rate ≥ 80％) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.

Quality evaluation of Bolbostemmatis Rhizoma by UPLC fingerprint combined with QAMS / 中国中药杂志

The present study was performed to establish the UPLC fingerprints of Bolbostemmatis Rhizoma and determine the contents of three saponins by quantitative analysis of multi-components by single marker(QAMS), and provide basis for quality evaluation of Bolbostemmatis Rhizoma. The analysis was carried out on an analytical column of Waters Cortecs T3(2.1 mm×100 mm,1.6 μm)with gradient elution by acetonitrile-0.1% phosphoric acid solution, at a flow rate of 0.3 mL·min~(-1). The detection wavelength was 203 nm, the column temperature was 30 ℃ and the injection volume was 1 μL. The UPLC fingerprints of Bolbostemmatis Rhizoma were established and evaluated by similarity calculation, cluster analysis and principal component analysis. The relative calibration factors of toberoside B and toberoside C were determined with toberoside A as internal reference. The content was calculated by relative calibration factors to develop a method of QAMS. Comparing the results of QAMS with those of ESM, the accuracy and feasibility of one-eva-luation and multi-evaluation can be determined. RESULTS:: showed that the fingerprints of 19 batches of Bolbostemmatis Rhizoma have four common peaks with similarities ranging from 0.754 to 1.000. Cluster analysis and principal component analysis classified 19 batches of Bolbostemmatis Rhizoma into three categories, which was consistent with the similarity evaluation results. The relative deviation between the content of tubeicosides B and C in 19 batches of Bolbostemmatis Rhizoma determined by QAMS and ESM is less than 5.0%, indicating that there was no significant difference between the two methods. Therefore, the UPLC fingerprints combined with QAMS and similarity evaluation can be effectively used to evaluate the quality of Bolbostemmatis Rhizoma.

A Prospective Observation of Psychological Distress in Patients With Anaphylaxis

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.

Increasing Prevalence and Mortality of Asthma With Age in Korea, 2002–2015: A Nationwide, Population-Based Study

PURPOSE: The prevalence of asthma is increasing globally as the world population increases; however, and the prevalence and mortality of asthma have not been extensively investigated. Also, the effects of severity and aging on asthma prevalence and mortality are unknown. We aimed to investigate trends of the prevalence and mortality of asthma as well as health care uses and costs over 14 years according to disease severity by using real-world data in Korea.METHODS: Using the National Health Insurance Sharing Service database, we extracted asthmatic patients having diagnosis codes of asthma and prescription records of antiasthmatic medications from 2002 to 2015 and categorized them according to asthma exacerbation and regular treatment. We defined asthma-associated death in terms of patients' prescription records within 3 months before all-cause death, then linked with the Cause of Death Statistics. The annual asthma-related health care uses and costs were analyzed.RESULTS: The prevalence rates of asthma (1.6% to 2.2%) and severe asthma (SA; 3.5% to 6.1% among total asthmatics) have increased steadily over the decade in Korea, where the proportion of elderly asthmatics having increased. The asthma-related health care uses and costs had increased during the study period with the highest uses/costs in SA. The asthma mortality had a steady rising trend from 16.2 to 28.0 deaths per 100,000 with the highest mortality in SA.CONCLUSIONS: The prevalence and mortality of asthma as well as SA increases along with the burden of health care uses/costs. More active interventions, including changes in health care policies, are needed to reduce the prevalence and mortality of asthma, especially SA.

Efficacy and Safety of a Pressurized Metered-Dose Inhaler in Older Asthmatics: Comparison to a Dry Powder Inhaler in a 12-Week Randomized Trial

PURPOSE: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.METHODS: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.RESULTS: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.CONCLUSION: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

Leisure Time Physical Activity to Reduce Metabolic Syndrome Risk: A 10-Year Community-Based Prospective Study in Korea

PURPOSE: Metabolic syndrome (MetS) is a major public health problem related to increased risks of cardiovascular disease and type 2 diabetes. We investigated whether recommended levels of leisure time physical activity (LTPA) decrease the risk of MetS in a community-based prospective cohort study (Ansung and Ansan cohort).MATERIALS AND METHODS: A total of 3910 adults (1890 men, 2020 women) without MetS examined in 2001–2002 (baseline) were included in this study and followed up from 2013 to 2014. We measured LTPA energy expenditure using the standard metabolic equivalent value [metabolic equivalent of task (MET)-h/wk]. Individuals were categorized into five groups (physically inactive, 0.1 to <7.5, 7.5 to <15.0, 15.0 to <22.5, 22.5 to <40.0, and ≥40.0 MET-h/wk).RESULTS: The mean follow-up period was 11.8 years. Among the cohort, 482 men (25.5%) and 541 women (26.8%) were diagnosed with newly developed MetS. Multivariate logistic analysis revealed a 4.4% lower MetS risk among those performing two to three times the recommended minimum of 7.5 MET-h/wk [multivariate relative risk (RR), 0.956; 95% confidence interval (CI), 0.654–1.398] and a 21.9% lower risk among those performing three to four times the physical activity minimum (multivariate RR, 0.781; 95% CI, 0.574–1.063). This association was only significant in females performing three to four times the minimum (crude RR, 0.655; 95% CI, 0.432–0.994).CONCLUSION: We noted that physical activity at more than 2 times the recommended minimum prevents MetS. Healthcare professionals should encourage inactive adults to be physically active during their leisure time to take advantage of its health benefits.