Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

This study used pharmacology combined with metabolomics to explore the effect of Amygdalus mongolica total extract on bleomycin induced pulmonary fibrosis in rats. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin and treated with the total extract of Amygdalus mongolica. The pathological changes of lung tissue were evaluated by hematoxylin and eosin (HE) and Masson staining, the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were detected, and transforming growth factor β1 (TGF-β1), Smad family member 3 (Smad3), α-smooth muscle actin (α-SMA) pathway index expression in lung tissue was detected by fluorescence quantitative PCR. UPLC-Q-TOF/MS was used to study serum metabolomics to explore the changing patterns of biomarkers and the metabolic pathways affected by them. The results showed that compared with the model group, the medium (1.5 g·kg^-1) and high (3.0 g·kg^-1) doses of Amygdalus mongolica total extract could significantly reduce the lung index, significantly increase the activity of SOD in serum and lung tissue, reduce the degree of alveolar inflammation and pulmonary fibrosis, and reduce MDA in serum and lung tissue, and significantly reduce TGF-β1, Smad3, α-SMA mRNA expression in lung tissue. Serum metabolomics profile analysis identified 25 significantly different metabolites, the Amygdalus mongolica total extract can participate in linoleic acid metabolism, glycerophospholipid metabolism and alpha-linolenic acid metabolism by reducing five key biomarkers: lysoPE(0∶0/22∶5(4Z,7Z,10Z,13Z,16Z)), lysoPC(20∶0/0∶0), PC(20∶5(5Z,8Z,11Z,14Z,17Z)/15∶0), 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOME), 9,10-dihydroxy-12-octadecenoic acid (9,10-DHOME) to affect pulmonary fibrosis. This study preliminarily revealed the action mechanism of Amygdalus mongolica total extract against pulmonary fibrosis in rats, and provided a reference basis for the clinical application of Amygdalus mongolica. The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College (No.20170315).

OBJECTIVEMacrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China.

METHODSFour macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23S rRNA and erm, were analyzed with nucleotide sequence analysis.

RESULTSVaried effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191A and T2221C on rrl were specific for the M. abscessus complex (MABC). Seven sites, G2140A, G2210C, C2217G, T2238C, T2322C, T2404C, and A2406G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192G, T2358G, and A2636G, were observed only in M. fortuitum and one site G2152A was specific for M. gordonae. The genes erm(39) and erm(41) were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar.

CONCLUSIONThe susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23S rRNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.

Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; China ; Drug Resistance, Bacterial ; Gene Expression Regulation, Bacterial ; Humans ; Macrolides ; pharmacology ; Mycobacterium ; drug effects ; genetics ; Polymorphism, Genetic

Objective: To investigate the regulation of JAK2 tyrosine kinase inhibitor ruxolitinib on extracellular matrix metalloproteinase (MMP in JAK2V617F positive myeloproliferative neoplasms (MPN) cells. Methods: ①Forty cases of newly diagnosed JAK2V617F positive MPN patients and 15 healthy volunteers as control in Baoding No.1 Hospital between January 2012 and December 2015 were enrolled in this study. JAK2V617F/JAK2 ratio was detected by real-time-PCR; the expression levels of phosphorylation protein tyrosine kinase 2 (p-JAK2) , MMP-2 and MMP-9 in pathological tissues of bone marrow were detected by immunohistochemistry. The bone marrow cells of JAK2V617F positive MPN patients were treated with ruxolitinib, then the migration ability and MMP-2, MMP-9 gene and protein expression levels were detected. ②The human erythroleukemia cell line HEL cells were treated with different concentrations of ruxolitinib (0, 50, 100, 250, 500, 1 000 nmol/L) . The cell viability was detected by CCK-8 test; cell migration ability was tested by transwell chambers. The mRNA expression levels of JAK2, MMP-2 and MMP-9 were detected by real-time-PCR. The protein expression levels of p-JAK2, MMP-2 and MMP-9 were detected by Western blot. Results: ①The expression levels of p-JAK2, MMP-2 and MMP-9 in the newly diagnosed group were significantly higher than control group respectively [ (78.56±24.55) % vs (41.59±17.29) %, P<0.05; (48.25±18.74) % vs (22.79±13.89) %, P<0.05; (53.29±19.28) % vs (15.56±14.96) %, P<0.05]. Spearman correlation analysis showed the positive correlation of MMP-2 and MMP-9 protein expression levels with JAK2V617F mutation (r=0.526, P=0.001; r=0.543, P=0.001) . ②The proliferation of HEL cells was inhibited by different concentrations of ruxolitinib in time and dose dependent manner. ③Cell migration test showed the number of cells leaked to the low chamber in MPN patients bone marrow cells and HEL cells treated with 5 nmol/L of ruxolitinib group were significantly lower than that without ruxolitinib treatment after 24 h [ (154.7±27.5) vs (320.3±67.3) , t=13.47, P<0.05; (70.7±10.5) vs (135.3±16.7) , t=13.89, P<0.05]. The mRNA and protein expression levels of JAK2, MMP-2 and MMP-9 decreased with the increased concentration of ruxolitinib. Conclusion Ruxolitinib inhibits MPN cell migration and expression of MMP-2 and MMP-9 via JAK2 signal pathway.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

Objective To investigate the prevalence of dyslipidemia in subjects with type 2 diabetes mellitus in Beijing urban communities.Methods Total 3316 subjects with type 2 diabetes (age 20-80 years) were recruited from 15 urban community health centers in Beijing using a multi-stage random sampling approach.Dyslipidemia was diagnosed according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults:2007 version.Results Among 3316 diabetic subjects (1329 malesand 1987 females),75.6％ (2506/3316) had dyslipidemia,the prevalence was 72.5％ (964/1329)in men and 77.6％ (1542/1987) in women.The prevalence of hypertriglyceridemia and hypercholesterolemia was 41.9％ (1388/3316) and 48.1％ (1595/3316),respectively.31.5％ (1043/3316) subjects had high levels of low-density lipoprotein cholesterol (LDL-C) and 21.2％ (703/3316) had low high-density lipoprotein cholesterol (HDL-C).Among all subjects with dyslipidemia only 22.9％ (575/2506) took hypolipid agents.The overall blood lipid control rates of triglyceride (TG),total cholesterol (TC),LDL-C and HDL-C in 1393 subjects with dyslipidemia history were 48.0％ (669/1393),17.4％ (242/1393),30.9％ (430/1393) and 75.8％ (1056/1393),respectively.Diabetics with dyslipidemia had higher body mass index,waist circumference,blood pressure,plasma glucose and hemoglobin A1c.The prevalence of dyslipidemia in the overweight and uncontrolled-glucose group were 79.0％ (1678/2125),78.9％ (1756/2227),respectively.Logistic regression analysis showed that gender,age,body mass index and hemoglobin A1c were associated with dyslipidemia.Conclusions The prevalence of dyslipidemia in diabetic subjects in Beijing urban communities is high and less than one quarter patients take hypolipid agents.Age,body mass index and hemoglobin A1c are the risk factors of dyslipidemia in type 2 diabetic patients.

Objective According to results from the two-month consecutive surveillance program in Maanshan,six suspected cases of non-O1 non-O139 Vibrio (V.) cholerae infection,were found that called for identification of pathogens as well as molecular-epidemiological analysis to determine the aggregation of the epidemic situation.Methods Biochemical and serotype identification,hemolysis test,and drug sensitive test were used to detect the drug resistance spectrum.Real-time PCR and conventional PCR were used to detect the presence of V.cholerae specific genes,virulent genes and its related genes,including ompW,ctx,tcpA,toxR,hlyA,zot,ace,rstR and g ⅢCTX.Pulsed-field gel electrophoresis (PFGE) was used to analyze the molecular type of strains.Results All the six isolates of non-O 1 non-O 139 V.cholerae were identified by biochemical and serologic tests,and appeared to be β hemolytic.Twelve out of the 14 kinds of drugs showed 100％ sensitive.All isolates were positive of ompW gene by real-time PCR,but negative for ctx,tcpA,zot,ace,rstR and gⅢ CTK.Five of the six isolates were positive for toxR and hlyA,except for strain 1001434446.All strains had different PFGE types,but two strains had similar types.All strains had a low similarity compared to the toxigenic V.cholerae.Conclusion Six cases ofnon-O1 and non-O139 nontoxigenic V.cholerae infection appeared in the same period.Along with epide(m)iological information,we noticed that these cases had a sporadic nature,but frequently appeared in the same area.We got the impression that public health measurements should be strengthened,with special attention paid to those diarrhea outbreaks caused by non-O 1 /non-O 139 strains since V.cholerae had appeared in low incidence.

Objective To investigate current status of use of oral hypoglycemic drugs and insulin among adult patients with type 2 diabetes mellitus (T2DM) in urban community of Beijing.Methods In total,3297 T2DM patients aged more than 20 years from 15 urban communities of Beijing were studied.Their body weight,height,fasting plasma glucose level and glycosylated hemoglobin Alc (HbAlc) were measured.A door-to-door questionnaire survey on use of oral hypoglycemic drugs and insulin was conducted for them.All the T2DM patients surveyed were divided into four groups based on their received intervention.Results ①Of 3279 T2DM patients,454 (13.8％) received lifestyle intervention,971 (29.5％) used only one oral hypoglycemic drug,1179 (35.7％) with combined oral hypoglycemic drugs,and 693(21.0％) with insulin.②There was significant difference in average HbAlc among the four groups of T2DM patients with lifestyle intervention,only one oral hypoglycemic drug,combined oral hypoglycemic drugs,and insulin,with HbAI c of (7.0 ± 1.9) ％,(7.1 ± 1.5) ％,(7.4 ± 1.5 ) ％,and (7.5 ± 1.5 ) ％for them,respectively ( F =15.1,P ＜ 0.01 ).Proportions of the T2DM patients with HbAlc equal to or higher than 7.0％ were 32.2％,39.4％,52.1％ and 59.5％ for the four groups,respectively ( x2 =117.7,P ＜ 0.01 ).③In the T2DM patients with lifestyle intervention,32.2％ (146/454) of them with HbA1 c equal to or higher than 7.0％ were untreated with any oral hypoglycemic drug.In those with only one oral hypoglycemic drug,39.4％ (383/971) of them with HbAlc equal to or higher than 7.0％ were not treated with combined oral hypoglycemic drugs and/or insulin.In those with combined oral hypoglycemic drugs,52.1％ (614/1079) of them with HbAlc equal to or higher than 7.0％ were not received combined insulin treatment.④ Fasting plasma glucose level,treatment strategies,postprandial 2-h blood glucose level and length of the illness were independent risk factors for HbAlc level equal to or higher than 7.0％,with odds ratio (OR) of 1.757,1.256,1.175 and 1.031,respectively.⑤ In 2843 T2DM patients with oral hypoglycemie drugs and/or insulin treatment,1494 (52.6％ ) received biguanides and 693 received (24.4％ )insulin,respectively.Conclusions More than half of adult patients with T2DM do not meet the target of glycemic control of HbAlc less than 7.0％ in urban communities of Beijing,due to not active use of oral hypoglycemic drugs,and not timely adoption of combined use of oral hypoglycemic drugs and insulin therapy.

Objective To study clinical characteristics of type 2 diabetic(T2D)patients with metabolic syndrome(MS)and its components in Beijing urban communities.Methods Totally,3295 T2D patients involved in a combined prospective diabetic management study from 15 urban communities in Beijing were classified as four groups, according to 2004 Chinese Diabetes Society's definition of MS, i. e, isolated T2D, T2D with one component of MS, T2D with two components of MS and T2D with three components of MS. Their clinical characteristics were analyzed. Results ( 1 ) Among 3295 T2D patients, 155 (4. 7% )were isolated T2D, 107 (32.6%) T2D with one component of MS, 1386 (42.1%) T2D with two components of MS and 679 (20.6%) T2D with three components of MS, with an overall 62.7% (2065/3295) of T2D patients complicated with MS. (2) In these T2D patients, the more components of MS they had, the higher body mass index (BMI), waist circumference, waist to hip circumference ratio (WHR),systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting serum levels of insulin and triglyceride (TG) and the lower level of high-density lipoprotein-cholesterol (HDL) were presented (P <0. 01 ). (3) Percentage of isolated T2D in women increased from 49. 0% (76/155) to 61.9% (420/679)of those with three components of MS ( P < 0 01 ), with increasing of components of MS. (4) Multiple logistic regression analysis showed that BMI, history of hypertension, decreased HDL, increased TG,increased blood pressure, all were risk factors for T2D patients complicated with MS. Conclusions Among T2D patients in urban communities of Beijing, 95.3% (3140/3295) of them complicated with one or more components of MS, and 61.9% (420/679) of them complicated with MS. So, community diabetic management must be implemented in an all-round way, including control of blood pressure, blood lipids,body weight and so on, in addition to control of blood sugar.

OBJECTIVETo observe the effect of the supernatant of heat injured keratinocytes (KC) on biological behavior of the dermal fibroblasts (Fb).

METHODSHuman dermal Fb were isolated and cultured. A model of heat injured KC (HaCaT) was reproduced in vitro. Supernatant of normal KC and the supernatant of KC culture 12 hours after heat injury were collected and diluted with non-serum DMEM in 1:1 volume ratio to make normal KC conditioned medium (NKCM) and heat injury KC conditioned medium (HKCM) respectively. Fb was respectively treated with non-serum DMEM and 2 kinds of conditioned medium. (1) The proliferation of Fb was detected with MTT method at post culture hour (PCH) 12, 24, 36, 48. (2) The apoptosis of Fb was determined by flow cytometry at PCH 12 (Fb were heat injured in advance; Fb without heat treatment was used as control). (3) At PCH 24, expression of a-SMA in Fb cytoplasm was determined with immunofluorescence method; expression of a-SMA mRNA in Fb was determined with real-time quantified PCR. Data were processed with one-way analysis of variance, and pairwise comparison among groups with LSD-t test.

RESULTS(1) The proliferation of Fb: the absorbance value of Fb cultured with HKCM at PCH 12, 24, 36, 48 was respectively higher than that of Fb cultured with non-serum DMEM (with t value respectively 1.89, 2.35, 2.02, 1.94, and P values all below 0.01). There were significant statistical differences between the absorbance values of Fb cultured with HKCM and those of Fb cultured with NKCM at PCH 12, 24, and 48 (at PCH 12, t = 1.83, P < 0.01; at PCH 24, t = 2.91, P < 0.05; at PCH 48, t = 1.83, P < 0.05). (2) Apoptosis of Fb cultured with HKCM was diminished as compared with that of Fb cultured with NKCM and of Fb without treatment (t = 3.31, P < 0.05; t = 1.47, P < 0.01). (3) The expression of alpha-SMA (red fluorescence) in Fb cultured with non-serum DMEM or NKCM was less as seen under fluorescence scope, and it was obviously increased in Fb cultured with HKCM. (4) The relative expression amount of alpha-SMA mRNA in Fb cultured with HKCM was 1.32 +/- 0.06, which was higher than that both in Fb cultured with NKCM (1.14 +/- 0.07, t = 2.51, P < 0.05) and in Fb cultured with non-serum DMEM (1.00 +/- 0.09, t = 1.77, P < 0.05).

CONCLUSIONSThe supernatant of KC 12 hours after heat injury can obviously promote the proliferation of Fb, inhibit its apoptosis and accelerate transdifferentiation of Fb to myofibroblasts.

Actins ; metabolism ; Apoptosis ; Cell Differentiation ; Cells, Cultured ; Culture Media, Conditioned ; pharmacology ; Fibroblasts ; cytology ; drug effects ; metabolism ; Flow Cytometry ; Heat Stress Disorders ; Hot Temperature ; adverse effects ; Humans ; Keratinocytes ; cytology ; RNA, Messenger ; genetics