A novel O-methyltransferase with substrate promiscuity from Ardisia japonica / 药学学报

italic>O-methyltransferases (OMTs) are one of the key tailoring enzymes in the biosynthesis of many natural products, O-methylation can not only reduce the reactivity of natural products, but also alter their solubility, stability and biological activities. Based on the transcriptome data of Ardisia japonica, a full-length cDNA sequence of candidate OMT (termed as AjOMT1) was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli (E. coli) for the first time. In vitro enzyme catalytic activity assay showed that the recombinant AjOMT1 could effectively catalyze quercetin to form O-methylated products. Most importantly, AjOMT1 showed unprecedented substrate promiscuity towards structurally various compounds including flavonoids, stilbenes, coumarins, alkaloids and phenylpropanoids, especially preferring to the compounds with adjacent phenolic hydroxyl groups, and showed regio-selectivity. These results suggested that AjOMT1 could be used as the tool enzyme to conduct O-methylation of different types of compounds to produce diverse active methylated products, and provide a new method for drug discovery, even universal part for synthetic biology of natural products.

Prognosis assessment of strong ion gap in adult patients with cardiac arrest / 中华急诊医学杂志

Objective:To investigate the correlation between strong ion gap (SIG) and prognosis of adult hospitalized patients who experienced cardiac arrest (CA).Methods:A retrospective cohort study was conducted on adult CA patients (≥18 years old) who were admitted to the intensive care unit (ICU) for the first time from the Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database from 2001 to 2012. The patients were divided into 3 groups based on the tertiles of serum SIG value. The clinical baseline characteristics and related data of CA patients were compared. Kaplan-Meier method was used to draw the 28- and 90-day cumulative survival curves of CA patients. Meanwhile, the log-rank test was used to compare the differences in the survival curves among different groups, and Cox proportional hazard regression model was established to analyze whether SIG was an independent predictor of all-cause mortality in CA patients.Results:Six hundred and six adult CA patients were eligible for final analysis. The patients were divided into 3 groups based on the tertiles of serum SIG value [<3.91 mmol/L ( n=202), 3.91~7.32 mmol/L ( n=202) and >7.32 mmol/L ( n=202)]. The mean age was (66.91±15.95) years and 382 patients (63.04%) were male. The all-cause mortality rates of ICU, 28 days and 90 days were 36.47%, 49.17% and 56.93%, respectively. There were significant differences in SOFA score, SIG, anion gap, pH, lactic acid, white blood cells, prothrombin time, creatinine, blood potassium, blood phosphorus, hypertension, coronary heart disease, cardiogenic shock, and ICU, 28-day and 90-day all-cause mortality among the 3 groups (all P<0.05). The Kaplan-Meier survival curves showed that the 28- and 90-day cumulative survival rates of CA patients decreased gradually with the increase of SIG level, and the differences were statistically significant among the 3 groups (all P<0.001). Multivariate Cox proportional hazard models showed that the increase of SIG level (>7.32 mmol/L) was an independent risk factor for 28-day ( HR=1.610, 95% CI: 1.177-2.203, P=0.003) and 90-day all-cause mortality ( HR=1.506, 95% CI: 1.123-2.019, P=0.006) among CA patients, after adjusting for the related confounders. Conclusions:The elevated SIG level (>7.32 mmol/L) is an independent predictor of 28- and 90-day all-cause mortality in CA patients. The calculation of SIG level in these patients is helpful for early identification of patients with poor prognosis.

Analysis of enterovirus infection type among acute respiratory tract infection cases in Luohe City, Henan Province from 2017 to 2021 / 中华预防医学杂志

Objective: To understand the infection status of Enterovirus (EV) in cases of acute respiratory infections (ARIs) in Luohe City, Henan Province from 2017 to 2021, and analyze the prevalence and type composition of EV in ARIs. Methods: From October 2017 to May 2021, pharyngeal swab samples were collected from 1 828 patients with ARIs in Luohe Central Hospital and the clinical epidemiological data of these cases were also collected. EV-positive samples were identified by Quantitative Real-time Polymerase Chain Reaction (qPCR). The 5'-untranslated region (5'UTR) was amplified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The results of 5'UTR region were initially typed by Enterovirus Genotyping Tool Version 1.0. Based on the typing results, the full-length of VP1 region was amplified by RT-PCR. The EV typing was identified again by VP1 region. Results: Among 1 828 cases of ARIs, 56.7% (1 036) were males. The median (Q1, Q3) age was about 3 (1, 5) years. Patients under 5 years old accounted for 71.6% (1 309 cases). Among all cases, a total of 71 EV-positive samples were identified by qPCR, with a detection rate of 3.88% (71/1 828). The EV detection rates for men and women were 3.28% (34/1 036) and 4.67% (37/792), without statistically significant differences (χ2=2.32, P=0.14). The EV detection rates for 2 to <6 years, 6 months to <2 years, 6 to <10 years, and <6 months were 6.29% (48/763), 3.00% (18/600), 2.52% (4/159), and 1.67% (1/60) (χ2=27.91, P<0.001). The EV detection rate was 0.92% (3/326) in autumn and winter of 2017. The EV detection rates were 1.18% (6/508), 2.47% (12/485) and 8.31% (34/409) in each year from 2018 to 2020, with an increasing trend year by year(χ2trend=29.76, P<0.001). The main prevalent seasons were summer and autumn. The detection rate in spring of 2021 was 4.00% (4/100). A total of 12 types were identified and classified as CVA2, CVA4, CVA5, CVA6, CVA10, CVB3, CVB5, E5, E11, E30, PV-1, and EV-D68. The types of CVA2, CVA10, CVA6, and CVB3 were the dominant phenotypes. In 59 sample of EV typing, the main clinical manifestation was upper respiratory tract infection (36/59, 61.01%). The dominant types detected in upper respiratory tract infections were CVA10 (10/36, 27.78%), CVA6 (9/36, 25.00%) and CVB3 (8/36, 22.22%). The dominant type detected in lower respiratory tract infections was CVA2 (7/19, 36.84%). Conclusion: In Luohe City, Henan Province from 2017 to 2021, EV infection in ARIs cases has clear seasonal and age-specific patterns, and the dominant types of upper and lower respiratory tract infections are different.

Correlation between macrophage chemotaxis and disease severity in patients with knee osteoarthritis / 中国骨伤

OBJECTIVE@#To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity.@*METHODS@#Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out.@*RESULTS@#The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01).@*CONCLUSION@#The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.

Prediabetes Progression and Regression on Objectively- Measured Physical Function: A Prospective Cohort Study

Background@#Prediabetes leads to declines in physical function in older adults, but the impact of prediabetes progression or regression on physical function is unknown. This study assessed this longitudinal association, with physical function objectivelymeasured by grip strength, walking speed, and standing balance, based on the Health and Retirement Study enrolling United States adults aged >50 years. @*Methods@#Participants with prediabetes were followed-up for 4-year to ascertain prediabetes status alteration (maintained, regressed, or progressed), and another 4-year to assess their impacts on physical function. Weak grip strength was defined as <26 kg for men and <16 kg for women, slow walking speed was as <0.8 m/sec, and poor standing balance was as an uncompleted fulltandem standing testing. Logistic and linear regression analyses were performed. @*Results@#Of the included 1,511 participants with prediabetes, 700 maintained as prediabetes, 306 progressed to diabetes, and 505 regressed to normoglycemia over 4 years. Grip strength and walking speed were declined from baseline during the 4-year followup, regardless of prediabetes status alteration. Compared with prediabetes maintenance, prediabetes progression increased the odds of developing weak grip strength by 89% (95% confidence interval [CI], 0.04 to 2.44) and exhibited larger declines in grip strength by 0.85 kg (95% CI, –1.65 to –0.04). However, prediabetes progression was not related to impairments in walking speed or standing balance. Prediabetes regression also did not affect any measures of physical function. @*Conclusion@#Prediabetes progression accelerates grip strength decline in aging population, while prediabetes regression may not prevent physical function decline due to aging.

Clinical analysis of 12 cases of invasive Klebsiella pneumoniae liver abscess syndrome / 中华全科医师杂志

Objective:To analyze the clinical features of patients with invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The clinical data of 12 patients diagnosed as IKLAS in Zhuzhou Central Hospital from January 2020 to January 2023 were retrospectively analyzed.Results:Among 12 patients there were 6 males and 6 females with an mean age of 65.3±12.2 years (49-90). Nine patients were complicated with type 2 diabetes. The main clinical manifestations were fever ( n=9), chill ( n=6), shiver ( n=4), nausea and vomiting ( n=2), upper abdominal pain ( n=2), fatigue and anepithymia ( n=2), cough and expectoration ( n=1), disturbance of consciousness ( n=1) and hemoptysis ( n=1). The leukocyte count was increased in 8 cases, lymphocyte count decreased in 10 cases, and platelets count decreased in 3 cases. C-reactive protein and procalcitonin levels were elevated, while serum albumin levels were lowered in all patients. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in 7 cases each. Liver abscess was located in the right lobe in 8 cases, in the left lobe in 1 cases, and in both lobes in 3 cases. There were 7 patients with single abscess, and 5 patients with multiple abscesses. The etiology was confirmed by liver pus culture ( n=10) and blood culture ( n=5), respectively. The main sites of invasion were lung and blood stream ( n=10 and n=5, respectively). The majority of Klebsiella pneumoniae isolates were antibiotic sensitive strains and the overall drug resistance rate was relatively low. All patients were given antibiotics, and 10 of them also received liver abscess puncture drainage. After treatment, 11 patients were discharged, and 1 died of septic shock. Conclusions:Patients with IKLAS exhibit diverse clinical symptoms, most patients are complicated with diabetes, and the main sites of invasion are in the lungs and blood stream. Timely diagnosis, active screening of extrahepatic infection sites, effective drainage of abscess and appropriate antibiotic treatment can improve the survival of patients.

Red cell distribution width and prognosis in patients with cardiac arrest: A retrospective cohort study / 中华急诊医学杂志

Objective:To investigate the association between the initial red cell distribution width (RDW) and all-cause mortality in patients with cardiac arrest (CA) in intensive care unit (ICU).Methods:We conducted a retrospective cohort study and extracted the related clinical data in ICU among adult CA patients (age ≥18 years), using the Multiparameter Intelligent Monitoring Intensive Care III (MIMIC-Ⅲ, v1.4) database from 2001 to 2012. Based on whether they survived or not on 90 days, the patients were divided into the survival group and death group, and the clinical data of the two groups were compared. Meanwhile, the RDW values were divided into four parts according to quartile. The cumulative survival rate of 28-day and 90-day were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazard models were also used to reveal the association between RDW and all-cause mortality.Results:Based on the inclusion and exclusion criteria, 853 adult CA patients were finally enrolled. The mean age was (67.26±15.84) years, and 534 (62.60%) patients were male. And the mean SOFA score was (6.13±3.70). Compared with the survival group ( n=410), the patients in the death group ( n=443) were older and had a higher SOFA score, RDW, anion gap, creatinine and blood phosphorus. Moreover, the proportion of chronic obstructive pulmonary disease, acute kidney injury and sepsis in the death group were higher than those in the survival group, and the length of stay in ICU in the death group was longer than that in the survival group (all P<0.05). However, the indicators of arterial blood oxygen partial pressure, hemoglobin and total blood calcium, as well as the proportion of coronary heart disease and acute myocardial infarction were lower than those in the survival group, and a shorter duration of hospitalization in the death group was noted (all P<0.05). Kaplan-Meier survival curves demonstrated that there was a significant difference in the cumulative survival rate of 28-day and 90-day (all P<0.001). In the multivariate Cox proportional hazard models, a higher RDW at ICU admission was an independent risk factor for 28-day ( HR=1.399, 95% CI: 1.014-1.930, P=0.041) and 90-day ( HR=1.433, 95% CI: 1.064-1.929, P=0.018) all-cause mortality among CA patients. Conclusions:An elevated RDW is an independent predictor for 28-day and 90-day all-cause mortality of CA patients. As a clinical indicators, it indicates a poor prognosis for adult CA patients.

The role of ROS/TXNIP/NLRP3 pathway in the skin injury of trichloroethylene sensitized mice / 中华劳动卫生职业病杂志

Objective: To explore the mechanism of reactive oxygen species/thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor 3 (ROS/TXNIP/NLRP3) pathway in the skin injury of trichloroethylene (TCE) sensitized mice. Methods: In August 2020, 40 female BALB/c mice were randomly divided into control group (n=5) , solvent control group (n=5) , TCE treatment group (n=15) and TCE+(2-(2, 2, 6, 6-Tetrameyhylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito TEMPO) treatment group (n=15) . The TCE sensitization model was established. Mice in the TCE treatment group and TCE+Mito TEMPO treatment group were divided into the sensitized positive group and the sensitized negative group according to the skin erythema and edema reactions on the back of the mice 24 h after the last stimulation. The mice were sacrificed 72 h after the last stimulation, the back skin of the mice was taken, and the skin lesions were observed. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3, and the Western Blot was performed to detect the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) , cysteinyl aspartate specific proteinase 1 (Caspase 1) , Interleukin-1β (IL-1β) and TXNIP proteins in the skin of the mice, the reactive oxygen species (ROS) kit was used to detect the level of intracellular ROS in the back skin tissue. Results: The sensitization rates of TCE treatment group and TCE+Mito TEMPO treatment group were 40.0% (6/15) and 33.3% (5/15) , respectively, and there was no significant difference between the two groups (P>0.05) . The back skin of the mice in the TCE sensitized positive group was thickened and infiltrated by a large number of inflammatory cells. The number of mitochondria in the epidermis cells was significantly reduced, the mitochondrial crest disappeared and vacuolar degeneration occurred. TCE+Mito TEMPO sensitized positive group had less damage, more mitochondria and relatively normal cell structure. Compared with the solvent control group and corresponding sensitized negative groups, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE sensitized positive group and TCE+Mito TEMPO sensitized positive group were significantly increased (P<0.05) . Compared with TCE sensitized positive group, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE+Mito TEMPO sensitized positive group were significantly decreased (P<0.05) . Conclusion: ROS/TXNIP/NLRP3 pathway was activated and then encouraged the release of IL-1β, finally aggravated the TCE-induced skin injury.

Normalized Creatinine-to-Cystatin C Ratio and Risk of Diabetes in Middle-Aged and Older Adults: The China Health and Retirement Longitudinal Study

Background@#Creatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort. @*Methods@#A population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed. @*Results@#During follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (Pinteraction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively. @*Conclusion@#High normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

Treatment plan of mycobacterium abscessus infection after autologous fat injection / 中华医学美学美容杂志

Objective:To explore an effective treatment method for mycobacterial infection of multiple abscesses in the face and breast after autologous fat injection.Methods:Six patients with non-tuberculous mycobacterial infection after autologous fat injection in the face and chest were treated from June to September in 2018. All patients underwent preoperative ultrasound localization. The small incision was opened for debridement and the necrotic granular tissues were completely scraped. Vacuum aspiration therapy in the sinus was used to promote wound growth, in line with the standard anti-tuberculosis drug treatment.Results:All six patients in this group were being followed up for 10-14 months. The average follow-up time was 12 months. All the infected patients were recovered, and the appearance of the infected site was satisfied by the patients.Conclusions:Small incision debridement with vacuum aspiration therapy combined with a variety of anti-tuberculosis drugs can effectively treat non-tuberculous mycobacterial infection after autologous fat injection, and achieve good results.

Efficacy of systemic glucocorticoid treatment and its related factors in patients with progressive vitiligo / 中华皮肤科杂志

Objective:To investigate the efficacy of systemic glucocorticoid treatment and its related factors in progressive vitiligo patients with vitiligo disease activity (VIDA) scores ≥ 2 points.Methods:A total of 272 progressive vitiligo patients with VIDA scores ≥ 2 points and skin lesion area < 1% of body surface area, who received no systemic glucocorticoid treatment, were collected from Department of Dermatology, the Third People′s Hospital of Hangzhou from June 2018 to June 2019. The area and type of skin lesions, VIDA scores, predisposing factors and special clinical markers (trichrome vitiligo, confetti-like depigmentation, Koebner phenomenon and inflammatory vitiligo) were analyzed. These patients were randomly divided into 3 groups by a random number table: topical glucocorticoid group (62 cases) , oral prednisone + topical glucocorticoid group (76 cases) and compound betamethasone injection + topical glucocorticoid group (134 cases) , and the latter two groups were also called as the systemic and topical glucocorticoid group. The patients in the topical glucocorticoid group were treated with halometasone cream or 0.05% clobetasol propionate cream once a day; during the oral prednisone treatment, the dose was adjusted once every 7 days, and gradually reduced from 30 mg/d to 20, 15, 10 and 5 mg/d, and the treatment lasted 35 days; during the treatment with compound betamethasone injection, intramuscular injection was performed once every 20 days at a dose of 1 ml for 2 sessions. The stable disease rate (defined as the proportion of patients experiencing no progression during the study among the analyzed patients) was calculated in these groups after 3 months of treatment, and changes in vitiligo types were evaluated after 1 year of follow-up. Statistical analysis was carried out by using Kruskal-Wallis H test, χ2 test and Fisher′s exact test. Results:After 3-month treatment, there was a significant difference in the expansion rate of skin lesion area among the 3 groups ( H = 12.468, P < 0.001) , and the expansion rate of skin lesion area was significantly lower in the oral prednisone + topical glucocorticoid group and compound betamethasone injection + topical glucocorticoid group than in the topical glucocorticoid group ( P < 0.001, = 0.005, respectively, α = 0.016 7) ; among the patients with slowly progressive vitiligo (VIDA scores = 2 or 3 points) , the stable disease rate was significantly higher in the systemic and topical glucocorticoid group than in the topical glucocorticoid group ( χ2 = 23.973, 11.877, respectively, both P < 0.001) ; the stable disease rate also significantly differed among the patients with different VIDA scores (VIDA scores = 2, 3 or 4 points) in the systemic and topical glucocorticoid group ( χ2 = 17.122, P < 0.001) . After 3-month treatment, the patients with predisposing factors or special clinical markers showed significantly decreased stable disease rate (47.3% [35/74], 41.2% [47/114], respectively) compared with those without predisposing factors or special clinical markers (70.6% [96/136], 87.5% [84/96]; χ2 = 11.098, 47.548, respectively, both P < 0.001) . After 1 year of follow-up, the proportion of patients with localized vitiligo converted into non-localized vitiligo was significantly higher in the topical glucocorticoid group (41.9%, 26/62) than in the systemic and topical glucocorticoid group (21.9%, 46/210; χ2 = 10.328, P = 0.006) , and higher in the group with predisposing factors or special clinical markers than in that without predisposing factors or special clinical markers respectively (both P < 0.01) . Conclusions:Early systemic glucocorticoid treatment should be performed in the progressive vitiligo patients with high VIDA scores, predisposing factors and special clinical markers.

Application of bronchoscopic lavage in children with severe adenovirus pneumonia / 中国小儿急救医学

Objective:To investigate the efficacy and safety of bronchoscopic lavage in children with severe adenoviral pneumonia.Methods:Patients with severe adenovirus pneumonia who were admitted to ICU department of Hunan Children′s Hospital for bronchoscopy were collected from February to June 2019 and divided into lavage group( n=36) and non-lavage group( n=15) in line with whether lavage was performed.Their results, namely, bronchoscopic diagnosis, blood gas analysis before and 2 hours, 24 hours and 48 hours after bronchoscopy, improvement time of clinical symptoms(fever and pulmonary moist rales), the positive rate of pathogen detection and mortality rate, main vital signs such as heart rate, respiratory rate, mean arterial pressure and bronchoscopy-related complications were recorded before and 1 hour, 2 hours and 24 hours after bronchoscopy. Results:A total of 51 children were collected, all of whom suffered from endobronchitis.More secretions were observed in the airways of 36 patients in the lavage group, and only a little or no secretions were observed in 15 patients in the non-lavage group.P/F value and PCO 2 at 2 hours, 24 hours and 48 hours after treatment in the lavage group were improved comparing to those before treatment and were superior to those in the non-lavage group( P<0.05). P/F values at 24 hours and 48 hours after treatment in the non-lavage group increased and PCO 2 decreased at 48 hours after treatment( P<0.05). The thermal duration, time to resolution of moist rales in the lungs in the lavage group were shorter than those in the non-lavage group( P<0.05). The mortality rate in the lavage group was lower than that in the non-lavage group[2.8%(1/36) vs.26.7%(4/15), P<0.05]. The positive rate of pathogen detection in lavage group was higher than that in non-lavage group[55.6%(20/36) vs. 20.0%(3/15), P<0.05]. There was no significant difference in heart rate, respiratory rate, and mean arterial pressure at each time point before and after bronchoscopic treatment( P>0.05). Associated complications were 11 cases of intraoperative transient hypoxemia, four cases of bronchial mucosal bleeding, and one case each of postoperative hypoxemia, intraoperative hypertension and hypotension.There was no significant difference in the incidence of complications between the two groups( P>0.05). Conclusion:Bronchoscopic lavage, in treating children with severe adenovirus pneumonia, may improve clinical symptoms, respiratory function, and rate of pathogen detection, reduce mortality, and is effective and safe.

Application of heparin-binding protein in severe adenovirus pneumonia / 中华实用儿科临床杂志

Objective:To explore the application value of heparin-binding protein (HBP) in the early diagnosis and assessment of severe adenovirus pneumonia.Methods:A total of 90 children diagnosed with adenovirus pneumonia admitted in the Department 1 of Emergency and Pediatric Intensive Care Unit 1 in Hunan Children′s Hospital from January 2019 to March 2020 were recruited.HBP levels in children with adenovirus pneumonia were detected.The correlation between HBP with white blood cell count (WBC), neutrophil ratio (N), C-reactive protein (CRP), interleukin-6(IL-6) and erythrocyte sedimentation rate (ESR) were examined.Receiver operating characteristic(ROC) curve analysis was conducted to explore the value of HBP in the early diagnosis and assessment of severe adenovirus pneumonia.Children with adenovirus pneumonia were divided into severe adenovirus pneumonia group (severe group) and non-severe adenovirus pneumonia group (non-severe group) according to their severity.Those in the severe group were further divided into bronchiolitis obliterans(BO) group and non-BO group according to the occurrence of BO.Results:(1) The HBP level in children with adenovirus pneumonia was (49.47±34.19) μg/L, which was significantly higher in the severe group than that of non-severe group[(82.88±44.02) μg/L vs.(35.15±13.08) μg/L, t=15.349, P<0.05]. Children in the severe group were significantly younger, and they had a significantly longer length of stay, lower Pediatric Critical Illness Scores (PCIS), and higher inflammatory markers like HBP, WBC, N, CRP, IL-6, and ESR compared with those of the non-severe group (all P<0.05). No significant difference in the procalcitonin (PCT) level was detected between groups.(2) The HBP was positively correlated with inflammatory markers like WBC ( r=0.38, P<0.05), N ( r=0.26, P<0.05), CRP ( r=0.47, P<0.05), IL-6 ( r=0.76, P<0.05), and ESR ( r=0.35, P<0.05). However, HBP did not have a significant correlation with PCT ( r=0.097, P>0.05). (3) In the severe group, the HBP level of the children with invasive mechanical ventilation, oxygenation index(P/F index)≤ 200 mmHg (1 mmHg=0.133 kPa) and BO was significantly higher than that of the non-invasive mechanical ventilation, P/F index> 200 mmHg and non-BO (all P<0.05). (4) The area under the ROC curve of HBP, WBC, N, CRP, ESR and IL-6 in predicting the severity of adenovirus pneumonia were 0.915, 0.748, 0.770, 0.740, 0.820 and 0.798, respectively.When the cut-off value of HBP was 45 μg/L, the sensitivity and specificity of HBP were 81.48% and 85.71%, respectively. Conclusions:As an inflammatory mediator, HBP is involved in the inflammatory response of the body.It may be a useful new marker for the early diagnosis of severe adenovirus infection, which also has a certain value in the evaluation of the severity and prognosis of the disease.The findings provide a basis for early clinical intervention and treatment of adenovirus infection in children.

Research Progress of Comprehensive Utilization of Ziziphi Spinosae Semen and Its By-products / 中国实验方剂学杂志

As a traditional Chinese medicine， Ziziphi Spinosae Semen （ZSS） has the functions of tonifying liver， tranquilizing heart， astringent sweat and producing body fluid， which is used to treat neurasthenia， insomnia， dreaminess， debility， night sweat and so on. With the rapid and constant development of ZSS resource industry and its medicinal value， a large number of by-products and waste generated in the production and processing process， resulting in serious environmental problems. In general， the utilization rate of ZSS resources was still not high. Based on this， the chemical components and potential resources of ZSS were systematically combed from the perspective of the medicinal parts and bioactive components in this paper， and the authors had summarized that the widely application of ZSS and its by-products （fruit， leaf， root， etc.） in the fields of food， medicine， functional food and other areas was discovered and summarized as feed， feed additives， activated carbon， organic fertilizer， etc. In addition， this paper systematically summarized the current environmental protection problems of the industry， and put forward suggestions for improvement， aiming at reducing environmental pollution and improving the utilization efficiency of resources， so as to provide reference and basis for the comprehensive utilization of ZSS and its by-products， and promote the green， economical and double-effect development of the industry.

Quantitative Classification of Murraya paniculata Leaf Traits and Endogenous Hormone Contents Analysis / 中国实验方剂学杂志

Objective:To carry out germplasm resource evaluation and new variety breeding of <italic>Murraya paniculata</italic> and improve the germplasm quality， so as to ensure the demand， yield and quality of medicinal materials. Method:Following resource investigation and collection， 17 traits of 107 <italic>M. paniculata</italic> germplasm samples， like plant type， basal diameter， leaf shape， leaf length， and leaf width were determined and then subjected to principal component analysis and factor analysis for screening the principal component factors. Nine primary traits were selected as variables for further cluster analysis using Ward's method and Euclidean distance. According to the characteristics of medicinal parts， the core germplasms were screened out. Then the contents of auxin， zeatin， zeatin nucleoside， isopentenyl adenine， isopentenyl adenine riboside， dihydrozeatin， and dihydrozeatinriboside in the leaves were measured by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， followed by their correlation analysis with agronomic trait. Result:The variation coefficients of petiole length， branching number， and basal diameter were large. The nine main factors could be classified into four categories， with a contribution rate of 72.822%. The cluster analysis with Ward's method and Euclidean distance showed that 107 germplasm samples were clustered into six clusters and 61 core germplasms were identified. Such traits as leaf length， leaf width， petiole length， leaf surface， and petiole color were found to play an important role in the classification of <italic>M. paniculata</italic> germplasms. The content of zeatin nucleoside exhibited significant positive correlations with leaf length （<italic>P</italic><0.01）， petiole length （<italic>P</italic><0.01）， and leaf width （<italic>P</italic><0.05）. Conclusion:These results have laid the foundation for further selection and breeding of <italic>M. paniculata</italic> new varieties.

Construction and application of recombinant human UDP-glucuronosyltransferases expression systems / 药学学报

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, 1H NMR, and 13C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

Clinical significance of EPHX2 deregulation in prostate cancer / 亚洲男科学杂志(英文版)

The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.

Application of organ-system-based curriculum design in the training of post competency for medical imaging / 中华医学教育探索杂志

Objective:To explore the teaching effect of organ-system-based curriculum (OSBC) on cultivating the post competency of radiologists.Methods:Based on the teaching design of OSBC, our study has completed the teaching practice for imaging diagnosis of prostate diseases, focal liver lesions, small pulmonary nodules and intestinal obstruction. The imaging diagnosis of prostate diseases was taken as teaching point. Fifty-two trainees were divided into four groups: junior standardized residents and clinical-type postgraduates (JSRCP) group, senior grade of standardized residents and clinical-type postgraduates (SG-SRCP), advanced training radiologist (ATR) group, intern doctors (ID) group. The teaching framework of pre-training assessment, training and post-training test was designed, and the teaching effect and the operability evaluation of OSBC was compared in terms of test scores and subjective evaluation before and after the training. SPSS 18.0 was used for t test. Results:The test scores after training of four groups were significantly improved compared to the test scores before training. The test scores of SG-SRCP group and ATR group were significantly higher than those of ID group ( F=16.609, P<0.001). The results of subjective evaluation showed that the SG-SRCP and ATR group had the highest degree of satisfaction. Conclusion:OSBC education mode has a good training effectiveness of middle and advanced stages course of medical imaging. In the future teaching, OSBC teaching should be explored among different levels of students.

Closed manipulative reduction and external fixation with cardboard splint for the treatment of Monteggia fracture / 中国骨伤

OBJECTIVE@#To explore clinical efficicacy of closed manipulative reduction and external fixation with cardboard splint in treating Monteggia fracture.@*METHODS@#Fifty-eight children with Monteggia fracture were underwent closed manipulative reduction and external fixation with cardboard splint from January 2010 to Junuary 2018. Among them, including 37 males and 21 females, aged from 3.5 to 12 years old with an average of (8.48±2.29) years old;the courses of disease ranged from 0.5 hours to 9 days with an average of (4.21±1.46) days. Broberg and Morrey scores before treatment, 1, 3 and 6 months after treatment were used to evaluate clinical effects.@*RESULTS@#All children were followed up from 1 to 6 months with an average of (3.35±2.12) months. Broberg and Morrey score (7.24±2.81) before treatment, (32.06 ±8.33) at 1 month after treatment, (73.18±5.56) at 3 months after treatment and (95.87±6.75) at 6 months after treatment; there were statistical differences at each time points after treatment with before treatment (@*CONCLUSION@#Treatment of Monteggia fractures with closed manipulative reduction and external fixation with cardboard splint could reach integration of motion and quietness, also could remove external fixation at early stage, and get obvious short-term and medium-term therapeutic results.