Semen parameters in men recovered from COVID-19 / 亚洲男科学杂志(英文版)

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Treatment of femoral periprosthetic fracture of Vancouver type B1 and C with bridge combined internal fixation system / 中国骨伤

OBJECTIVE@#To evaluate the clinical effect of bridge combined internal fixation system in the treatment of periprosthesis fracture of femur after hip replacement.@*METHODS@#From October 2016 to June 2018, 5 patients of periprosthesis fractures of femur classified type B1 and type C in Vancouver were treated by open reduction and bridging combined with internal fixation, including 2 males and 3 females, with ages of 68, 70, 74, 75, 79 years;type B1 fractures in 4 and type C fractures in 1. Causes of injury:1 case of traffic injury, 4 cases of fall. After the operation, the patients were followed up for complications and fracture healing time by clinical and imaging examination, and Parker activity score was performed.@*RESULTS@#The wounds of 5 patients healed without infection. One case of DVT was confirmed by venography. Five patients were followed up, and the durations were 2, 8, 9, 10, 15 months. One patient died of myocardial infarction 2 months after operation. The average healing time was 12.5 weeks. No loss of reduction or failure of internal fixation was found. Two patients could walk without protection and 1 patient needed to rely on single crutch. One case of periprosthetic fracture had to walk with a single crutch before operation and move indoors with two crutches after operation. The average Parker activity score was 51.8% before operation.@*CONCLUSION@#The bridge combined internal fixation system can be used to fix the fracture after hip replacement with stable femoral prosthesis.

MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy / 中华医学杂志(英文版)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, placing an increasing burden on human health. NAFLD is a complex multifactorial disease involving genetic, metabolic, and environmental factors. It is closely associated with metabolic syndrome, obesity, and type 2 diabetes, of which insulin resistance is the main pathophysiological mechanism. Over the past few decades, investigation of the pathogenesis, diagnosis, and treatments has revealed different aspects of NAFLD, challenging the accuracy of definition and therapeutic strategy for the clinical practice. Recently, experts reach a consensus that NAFLD does not reflect the current knowledge, and metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested as a more appropriate term. The new definition puts increased emphasis on the important role of metabolic dysfunction in it. Herein, the shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy of the newly defined MAFLD, as compared with the formerly defined NAFLD, are reviewed for updating our understanding.

Clinical features of different isoforms of PML鄄RARα fusion gene in patients with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective To explore the clinical features and prognosis of different PML_RARα fusion gene isoforms in acute promyelocytic leukemia (APL). Methods The clinical data of 78 patients initially diagnosed with APL in Fujian Medical University Union Hospital from February 2013 to July 2016 were collected. The clinical features and prognosis of different PML_RARα fusion gene isoforms were analyzed. Results There were 32 females (41%) and 46 males (59%) in 78 patients, with a median age of 40 years old (13-68 years old). The most common PML_RARα fusion gene was L type (48.7%, 38/78), followed by S type (46.2%, 36/78) and V type (5.1%, 4/78). The patients with white blood cell count more than 10×109/L (high_risk) occurred mostly in S type (61.1%, 22/36), compared with V type and L type, and there were statistically different (χ 2 ＝ 7.683, P < 0.05). A total of 78 patients included 8 cases (10.2%) of combined CD34 positive, 17 cases (21.8%) of combined FLT3_ITD mutation, 12 cases (15.4%) of combined DNMT3A mutation and 9 cases (11.5%) of additional chromosomal abnormalities. There were no significant differences in CD34 positive, FLT3_ITD, DNMT3A, and the incidence of additional chromosomal abnormalities among the three different isoforms (P＞0.05). The most common occurrence of retinoic acid syndrome (RAS) during treatment was S type (21/36), while rare for L type and V type (χ2＝ 7.633, P< 0.05). There were no statistical differences in the complete remission (CR) rate and disease_free survival rate among the patients with different PML_RARα isoforms (P＞0.05). Conclusions The clinical characteristics of different PML_RARα fusion gene isoforms are different, including most_common L type, more_common V type and S type in high risk groups; complicated RAS is commonly found in S type during the treatment. And different isoforms have no effect on the CR and DFS rate.

Effect of caveolin-1 scaffolding domain peptides on heme oxygenase-1 activity increasing and M1/M2 phenotype polarization in rat alveolar macrophages induced by lipopolysaccharide / 中华危重病急救医学

Objective To investigate the effect of caveolin-1 scaffolding domain (CSD) peptides on heme oxygenase-1 (HO-1) activity increasing and M1/M2 phenotype polarization in rat alveolar macrophages (AMs) induced by lipopolysaccharide (LPS).Methods Bioinformatics was used to analyze the binding of full-length wild-type CSD polypeptide and 101 amino acid deleted truncated mutant CSD polypeptide (Δ101CSD) to HO-1. Primary AMs were isolated from rats, when cell fusion reached 80％, they were synchronized with serum-free medium and divided into five groups: no treatment was given to the blank control group; LPS group was treated with 100μg/L LPS for 16 hours;LPS+ hemin group was treated with 100μg/L LPS and 20μmol/L hemin for 16 hours; wild-type CSD polypeptide+ LPS+hemin group was pretreated with 10μmol/L wild-type CSD polypeptide 6 hours before LPS treatment; Δ101CSD+ LPS+hemin group was pretreated with 10μmol/L Δ101CSD polypeptide 6 hours before LPS treatment. After treatment for 16 hours, the co-localization between caveolin-1 (Cav-1) and HO-1 was displayed by confocal microscope; the mRNA expressions of inflammatory cytokines interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) and M1/M2 polarization cytokines tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), leukocyte differentiation antigen 206 (CD206) and IL-10 were determined by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-qPCR); the HO-1 activity and nitric oxide (NO) production were determined by spectrophotometry.Results Bioinformatics analysis showed: both wild-type CSD and Δ101CSD peptides could bind to HO-1, and there was no significant difference in the binding ability between the two peptides, but the deletion of 101 Arg resulted in the disappearance of part of the binding region between Δ101CSD and HO-1. The results of laser confocal microscopy showed: the expressions of Cav-1 and HO-1 were lowed in the blank control group, and Cav-1 was bound to HO-1 in LPS group and LPS+ hemin group. Both wild-type CSD and Δ101CSD peptides pretreatment could significantly reduce the binding of HO-1 to Cav-1 induced by LPS. HO-1 activity analysis showed: after LPS stimulation, the activity of HO-1 was significantly higher than that of the blank control group; the activity of HO-1 induced by LPS was increased by hemin; after pretreatment with two kinds of CSD peptides, the activity of HO-1 was further increased, and the effect of wild-type CSD peptide was more significant, which showed a statistically significant difference as compared with that of LPS+ hemin group (pmol·mg-1·h-1: 3683±266 vs. 2408±132,P < 0.05). RT-qPCR results showed: LPS could induce elevation of cytokines and M1 markers and decrease of M2 markers, while hemin could inhibit LPS-induced inflammatory response and M1/M2 phenotypic polarization. Compared with LPS+ hemin group, after pretreatment with wild-type CSD peptide, the levels of inflammatory factors in AMs were decreased, and the mRNA expression levels of TNF-α and iNOS, M1 markers, were decreased [TNF-α mRNA (2-??Ct): 6.82±0.05 vs. 8.70±0.24, iNOS mRNA (2-??Ct): 331.50±32.05 vs. 506.70±0.10, bothP < 0.05], and IL-10 mRNA expression level was increased (2-??Ct: 269.09±6.54 vs. 119.05±3.30,P < 0.05). The deletion of 101 site partially weakened the inhibitory effect of CSD peptides on inflammatory factors and only reduced the expression of iNOS mRNA (2-??Ct: 429.11±8.92 vs. 506.70±0.10,P < 0.05), indicating that its ability to transform AMs from M1 phenotype to M2 phenotype was poor. The two peptides had no effect on the expression of CD206.Conclusion Wild-type CSD had beneficial effects of anti-inflammation by reducing Cav-1 binding to HO-1 induced by LPS, restoring the HO-1 activity and driving M2 phenotype in alveolar macrophages.

The Predictive Value of Carotid Plaque Score for Evaluating the Severity of Coronary Artery Lesions / 中国循环杂志

Objective:To study the predictive value of carotid plaque score for evaluating the severity of coronary artery lesions.Methods:A total of 152 patients with coronary angiography diagnosed coronary artery disease (CAD) in our hospital from 2016-01 to 2016-05 were selected.According to coronary branch involvement,the patients were divided into 3 groups:Single branch lesion group,n=72,Double branch lesion group,n=38 and Multi branch lesion group,n=42.The basic conditions as plaque detection rate,high-density lipoprotein cholesterol (HDL-C),body mass index (BMI) were collected and carotid ultrasound examination was conducted in all patients.Carotid plaque condition and coronary lesion degree were calculated by semi-quantitative score and Gensini score methods;the relationship between semi-quantitative score and Gensini score was compared.Results:Total cholesterol (TC),HDL-C,LDL-C and BMI were similar among different groups,P＞0.05.Compared with Single branch lesion group,Double branch lesion group and Multi branch lesion group had more smokers and the higher plaque detection rate,P＜0.05.Semi-quantitative score and Gensini score were elevating as coronary lesion branch increasing accordingly.Conclusion:The severity of coronary lesions could be evaluated and predicted by semi-quantitative calculation of carotid integral.

The Predictive Value of Carotid Plaque Score for Evaluating the Severity of Coronary Artery Lesions / 中国循环杂志

Objective:To study the predictive value of carotid plaque score for evaluating the severity of coronary artery lesions.Methods:A total of 152 patients with coronary angiography diagnosed coronary artery disease (CAD) in our hospital from 2016-01 to 2016-05 were selected.According to coronary branch involvement,the patients were divided into 3 groups:Single branch lesion group,n=72,Double branch lesion group,n=38 and Multi branch lesion group,n=42.The basic conditions as plaque detection rate,high-density lipoprotein cholesterol (HDL-C),body mass index (BMI) were collected and carotid ultrasound examination was conducted in all patients.Carotid plaque condition and coronary lesion degree were calculated by semi-quantitative score and Gensini score methods;the relationship between semi-quantitative score and Gensini score was compared.Results:Total cholesterol (TC),HDL-C,LDL-C and BMI were similar among different groups,P＞0.05.Compared with Single branch lesion group,Double branch lesion group and Multi branch lesion group had more smokers and the higher plaque detection rate,P＜0.05.Semi-quantitative score and Gensini score were elevating as coronary lesion branch increasing accordingly.Conclusion:The severity of coronary lesions could be evaluated and predicted by semi-quantitative calculation of carotid integral.

Effects of caveolin-1 scaffolding domain peptide on LPS-induced acute lung injury in mice / 中国病理生理杂志

AIM: To investigate the effects of caveolin-1 (Cav-1) scaffolding domain peptide, cavtratin, on lipopolysaccharide (LPS)-induced mouse acute lung injury and heme oxygenase-1 (HO-1) activity.METHODS: Adult male BALB/c mice were randomly divided into 6 groups (n=8 to 10): control, Antennapedia internalization sequence (AP), LPS, LPS+hemin, LPS+ hemin+cavtratin and LPS+hemin+cavtratin+zinc protoporphyrin IX (ZnPP) groups.After LPS administration for 24 h, the lung pathological changes, the wet/dry weight (W/D) ratio of lung tissues, total cell number in bronchoalveolar lavage fluid and serum lactate dehydrogenase activity were measured.The co-localization of HO-1 and Cav-1 was displayed by immunofluorescence, and the HO-1 activity were detected.The mRNA expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, MCP-1 and iNOS was detected by real-time PCR.RESULTS: The mice in LPS+hemin+cavtratin group had the decreased interaction between HO-1 and Cav-1, and the increased HO-1 activity compare with LPS group (P<0.05).Compared with LPS group, the pulmonary damage was attenuated in LPS+hemin+cavtratin group, and the injury indexes, including W/D ratio, total cell number in bronchoalveolar lavage fluid and lactate dehydrogenase activity in the serum, and the mRNA expression of inflammatory cytokines all decreased (P<0.05).HO-1 activity inhibitor ZnPP abolished the above protective effect of cavtratin on the lung tissues with LPS-induced acute lung injury.CONCLUSION: Cavtratin has beneficial effects on the lung with LPS-induced acute injury by restoring the HO-1 activity.

Protective effects of methylene blue on ischemia/reperfusion-induced mitochondrial injury in isolated rat hearts / 中国病理生理杂志

AIM:To study the effects of methylene blue (MB) on myocardial ischemia/reperfusion (I/R)-induced mitochondrial injury in isolated rat hearts.METHODS:Spragure-Dawley (SD) rats were divided into 3 groups randomly (n=6): control group, I/R model group and MB treatment group (IR+MB group).The isolated rat hearts were prepared and set up to Langendorff perfusion.The rats in I/R+MB group received MB (2 mg/kg) by intraperitoneal injection 2 h before operation.The hearts in control group were perfused with K-H solution for 110 min consecutively.The hearts in I/R group and I/R+MB group were in equilibrium for 20 min, following by 45 min of global ischemia, and then reperfused for 60 min.The heart rate (HR), left ventricular developed pressure (LVDP), left ventricular pressure maximum change rate (±dp/dtmax) and left ventricular end-diastolic pressure (LVEDP) were recorded.The perfusate was collected to determine the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH).The contents of reactive oxygen species (ROS), malondialdehyde (MDA) and adenosine triphosphate (ATP), and the activity of superoxide dismutase (SOD) in the myocardial tissues were all determined.Histopathological examination of left ventricle was performed.The mitochondria from the heart tissues was isolated and the mitochondrial swelling and mitochondrial membrane potential (MMP) were analyzed.RESULTS:Compared with control group, the hearts in I/R group showed poorer function, higher CK-MB and LDH levels in the perfusate, increased ROS and MDA contents, higher SOD activity and less ATP content in the heart tissues (P<0.05).Furthermore, the mitochondrial swelling level increased and MMP reduced in I/R group (P<0.05).Compared to I/R group, MB improved heart function and reduced the release of CK-MB and LDH (P<0.05).MB also decreased ROS and MDA contents, and increased the activity of SOD and the content of ATP (P<0.05).In addition, MB alleviated mitochondrial swelling and restored the reduced MMP (P<0.05).CONCLUSION: MB protects the isolated rat hearts from I/R-induced injury by attenuating the damage of mitochondria.

Correlation between pathologic features and contrast-enhanced ultrasound in patients with breast ductal papilloma / 实用医学杂志

Objective To investigate the correlation between pathologic features and contrast?enhanced ultrasound in patients with breast ductal papilloma. Methods From January 2014 to January 2016,80 patients with breast intraductal tumor treated in our hospital were selected,including 20 cases of breast ductal carcinoma (ductal carcinoma group) and 60 cases of benign tumor (benign group). Both groups received conventional ultrasound, ultrasonic angiography,and pathological feature analysis. Results Breast surrounding hyperecho,internal micro calcification,border edge burr and posterior echo attenuation were more frequently seen onconventional ultrasound in ductal carcinoma groupthan inbenign group(P<0.05). The average scores of contrast?enhanced ultrasound were significantly higher in ductal carcinoma group than in the control group(P<0.05). In the ductal carcinoma group, there were statistical significant differences betweenpatientswith different lymph node metastasis dukes staging ,and differentiation types (P < 0.05). Spearman rank correlation coefficient analysis showed that breast intraductal carcinoma lymph node metastasis and dukes staging,differentiation types were markedly correlated with pathological features and ultrasound imaging (r=0.341,0.368,and-0.289;P<0.05). Conclusions Conventional ultrasound and contrast?enhanced ultrasound have very good imaging featuresin the diagnosis of breast intraductal cancer ,and there is correlation between pathologic features and contrast?enhanced ultrasound in patients with breast ductal papilloma,which can provide values for early diagnosis of breast ductal carcinoma.

Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI.</p><p><b>METHODS</b>Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment.</p><p><b>RESULTS</b>Lungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P< 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P< 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P< 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P< 0.001, and P< 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P< 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-β) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P< 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group).</p><p><b>CONCLUSION</b>BV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.</p>

Effectiveness of different waist circumference cut-off values in predicting metabolic syndrome prevalence and risk factors in adults in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China.</p><p><b>METHODS</b>A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria.</p><p><b>RESULTS</b>The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions.</p><p><b>CONCLUSION</b>Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.</p>

Effect of water extracts from duhuo jisheng decoction on expression of chondrocyte G1 phase regulator mRNA / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of water extracts from Duhuo Jisheng decoction on chondrocyte G1 phase.</p><p><b>METHODS</b>Chondrocytes were collected from four-week-old SD rats to establish the chondrocyte in vitro culture system. The third generation of chondrocytes was intervened. MTT method was used to measure the effect of water extracts from different concentrations of Duhuo Jisheng decoction on chondrocyte activity. The expressions of Chondrocyte Cyclin D1, CDK4, CDK6 and P21 mRNA in the blank group and low, middle and high-dose groups (100, 200, 400 mg x L(-1)) were detected by RT-PCR method.</p><p><b>RESULT</b>The MTT assay showed that the chondrocyte activity significantly increased within specific drug concentrations (50-800 mg x L(-1)) (P < 0.01); After the intervention for 24 h, the expressions of CyclinD1, CDK4 and CDK6 mRNA in all dose groups notably increased (P < 0.05), with the maximum expressions at the concentration of 200 mg x L(-1); The expression of P21 mRNA decreased, particularly at the concentration of 200 mg x L(-1) (P < 0.01).</p><p><b>CONCLUSION</b>Water extracts from Duhuo Jisheng decoction can promote chondrocyte proliferation by effecting the expression of chondrocyte G1 phase regulator mRNA.</p>

The experimental study of suppressing silicosis fibrosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To compare the difference of effects on SiO(2)-induced alveolitis and early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs) and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this effects.</p><p><b>METHODS</b>The Primary BM-MSCs from Wistar male young rats were cultured and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were randomly divided into 3 groups:model group (10 rats),which was administered with SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On the 14th and 28th days after treatment, half of the animals were sacrificed, respectively, and the lungs were harvested for frozen section to observe the cell marked by DAPI. HE staining under a fluorescent microscope, and to observe the pulmonary alveolitis and fibrosis by HE and Masson staining under a light microscope. Western blot assay was used to detect the expression of HGF in rat lungs. The expression levels of tumor necrosis factor-α (TNF-α) in pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in pulmonary tissues were analyzed quantitatively by sample hydrolysis method.</p><p><b>RESULTS</b>On the 14th and 28th days after treatment, the scores of pulmonary alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 ± 0.17, 2.8 ± 0.14 and 0.1 ± 0.11, 1.16 ± 0.13, which were significantly lower than those (1.68 ± 0.17, 1.58 ± 0.31 and 0.54 ± 0.15, 1.36 ± 0.13) in BM-MSCs group, also which were significantly lower those (2.36 ± 0.17, 2.80 ± 0.14 and 0.64 ± 0.09, 1.84 ± 0.17) in model group (P < 0.05); On the 14th and 28th days after treatment, the TNF-α contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 280.4 ± 23.11 and 249.78 ± 22.33 pg/mg, which were significantly lower than those (341.58 ± 35.34, 442.29 ± 36.76 pg/mg and 319.51 ± 17.84, 348.53 ± 33.95 pg/mg) in BM-MSCs and model groups (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 ± 0.04 and 0.65 ± 0.05 µg/mg, which were significantly lower than those (0.63 ± 0.04, 1.04 ± 0.07 µg/mg and 0.72 ± 0.60, 1.39 ± 0.60 µg/mg) in BM-MSCs and model groups (P < 0.05).</p><p><b>CONCLUSION</b>The effects of BM-MSCs transfected by pcDNA3.1-HGF on suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary inflammation.</p>

Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case with ovarian cystadenoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Laminopathies are a group of rare genetic disorders characterized by multiple-tissue degeneration. We describe a new laminopathy with ovarian cystadenoma and explore its molecular etiology.</p><p><b>METHODS</b>The case is a 15-year-old girl who presents the prominent progeroid disorders, multiple system degeneration and early-onset cystadenoma of the ovary. Candidate genes including LMNA, ZMPSTE24, PPAR G, INSR and WRN were sequenced to screen for DNA variants. The mRNA and protein expression levels of LMNA were examined in primary fibroblasts. The pathophysiological events such as morphologic alterations, cell senescence, cell proliferation, apoptosis and pRb as well as p53 protein expressions were also investigated in primary fibroblasts.</p><p><b>RESULTS</b>No mutation was identified in the candidate genes screened. Nuclear abnormalities including nuclear blebs, mislocalization of lamin A/C were evident in the patient fibroblasts. Ultrastructurally, nucleus exhibited nuclear herniation and almost complete loss of peripheral heterochromatin. In addition, lamin C protein expression was markedly reduced whereas lamin A protein level was normal and no prelamin A was detected in the primary fibroblasts. Although the senescence-associated beta-galactosidase staining of patient' cells was negative, cells in S phase increased in accompany with a decrease in pRb protein expression. Furthermore, increases in apoptotic cell death and p53 expression were observed.</p><p><b>CONCLUSIONS</b>Our data suggest that selective deficiency of lamin C protein is associated with a case of laminopathy with ovarian cystadenoma. The abnormalities in nuclear structure and alterations in gene expression such as the decrease in pRb and increase in p53 may be responsible for the multiple tissue degeneration.</p>

Exchange of a nuclear corepressor between NF-kappaB and CREB mediates inhibition of phosphoenolpyruvate carboxykinase transcription by NF-kappaB / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>NF-kappaB p65 was shown to inhibit transcription of phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis in the liver. To understand the mechanism of action of NF-kappaB p65, we investigated the nuclear receptor corepressor in the regulation of PEPCK transcription.</p><p><b>METHODS</b>Rat H4IIE cells, human hepatoma HepG2 cells and human embryo kidney (HEK) 293 cells were used in this study. The transcriptional activity of a rat PEPCK gene promoter (-490/+100) was analyzed in HepG2 cells, a HepG2 super suppressor IkBalpha (ssIkBalpha) stable cell line, and HEK 293 cells. The effects of p65 and ssIkBalpha on a rat PEPCK gene promoter were observed using the PEPCK luciferase reporter system. The interaction of the cAMP-response- element-binding (CREB) protein, histone deacetylase 3 (HDAC3) and silencing mediator for retinoic and thyroid hormone receptors (SMRT) with the PEPCK gene promoter were investigated using the chromatin immunoprecipitation (ChIP) assay. p65 cotransfection and RNAi-mediated gene knockdown were used to determine the corepressor involved in the inhibition of PEPCK by NF-kappaB p65 and the transcriptional regulation of CREB by NF-kappaB p65.</p><p><b>RESULTS</b>NF-kappaB p65 inhibited PEPCK expression and the inhibition was blocked by ssIkBalpha. The inhibitory effect of p65 was completely blocked in a HepG2 stable cell line in which ssIkBalpha was expressed. HDAC3 or SMRT knockdown led to a significant up-regulation of PEPCK reporter activity in the presence of p65 cotransfection. In the ChIP assay the interaction of HDAC3 and SMRT with the PEPCK gene promoter was induced by p65 activation, but the CREB signal was reduced. Transcriptional activity of CREB was inhibited by NF-kappaB p65 cotransfection. The inhibitory effect of NF-kappaB p65 was blocked by HDAC3 RNAi or SMRT RNAi.</p><p><b>CONCLUSIONS</b>The study showed that the inhibition of PEPCK by NF-kappaB p65 was dependent on HDAC3 and SMRT, which form a nuclear corepressor complex for transcriptional inhibition. The transcription factors NF-kappaB p65 and CREB share the same corepressor HDAC3-SMRT, and the corepressor exchange leads to inhibition of PEPCK gene transcription by NF-kappaB p65.</p>

Effects of leptin on RAAS and nitric oxide production in isolated rat glomeruli / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in angiotensinogen (AGT), angiotensin II type 1 receptor (AT(1)R), endothelial nitric oxide synthase (eNOS) mRNA and protein expressions and nitric oxide (NO) content in the rat glomeruli in response to leptin stimulation.</p><p><b>METHODS</b>The glomeruli isolated from male SD rats were stimulated with 3 nmol/L leptin for 2 h. Real-time PCR and Western blotting were performed to analyze the mRNA and protein expressions of AGT, AT(1)R and eNOS in the glomeruli, and nitrite concentration in the glomeruli was measured by nitrate reductase assay.</p><p><b>RESULTS</b>In comparison with the control group, exposure to leptin increased the mRNA levels of AGT, ATR(1) and eNOS in the isolated glomeruli by 2.69-/+0.17, 3.77-/+0.16 and 2.56-/+0.29 folds (P=0.024, 0.018 and 0.044), and their protein levels by 2.06-/+0.10, 2.67-/+0.08 and 1.61-/+0.13 folds (P=0.021, 0.015 and 0.032), respectively. The NO production in the glomeruli was also increased by 2.77-/+0.14 folds (P=0.000) following leptin exposure.</p><p><b>CONCLUSION</b>Leptin exposure of isolated rat glomeruli directly causes activation of the internal renal renin-angiotensin system and enhanced NO production, suggesting that leptin plays a role in the pathogenesis of maladaptation in renal hemodynamics in obesity.</p>

Remission of hyperglycemia following intensive insulin therapy in newly diagnosed type 2 diabetic patients: a long-term follow-up study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve beta-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and beta-cell function and assess the variables predictive of long-term near-normoglycemic remission.</p><p><b>METHODS</b>Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion (CSII) and followed up longitudinally. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, hemoglobin A1c (HbA1c) and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group.</p><p><b>RESULTS</b>The duration to be diagnosed of the patients (from the time that patients began to have diabetic symptoms until diagnosis) in the remission group was shorter than that in the non-remission group (1.00 month vs 4.38 months, P = 0.040). The increase of the acute insulin response (AIR) was maintained after 2 years in the remission group compared with AIR measured immediately after intervention (413.05 pmol*L(-1)*min(-1) vs 408.99 pmol*L(-1)*min(-1), P = 0.820). While AIR in the non-remission group significantly declined (74.71 pmol*L(-1)*min(-1) vs 335.64 pmol*L(-1)*min(-1), P = 0.030). Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio (OR) 1.019, P = 0.038, while fasting plasma glucose (FPG) and post-breakfast plasma glucose (PPG) after CSII were the risk factors (OR 1.397, P = 0.024 and OR 1.187, P = 0.035, respectively).</p><p><b>CONCLUSION</b>The near-normoglycemic remission is closely associated with long-term maintenance of beta-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.</p>

Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A new inhalable insulin aerosol (Inh-Ins) was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes. Regular porcine insulin (RI) was used as a control.</p><p><b>METHODS</b>This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks. HbA1c, fasting plasma glucose (FPG), the 1-hour-postprandial blood glucose (1hPBG) and the 2-hour-postprandial blood glucose (2hPBG) were measured. Events were monitored for adverse effects.</p><p><b>RESULTS</b>After 12 weeks, the HbA1c decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-Ins group, FPG, both 1hPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity (DLco) was significantly lower in Inh-Ins group than in the RI. The main side effects of Inh-Ins were coughing, excessive sputum, and hypoglycemia.</p><p><b>CONCLUSIONS</b>Inh-Ins was effective in decreasing HbA1c like the RI. It was better in lowering the FPG and the 1hPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-Ins slightly impaired DLco.</p>

Effects of gene transfer CTLA4-Ig and anti-CD154 monoclonal antibody on the rejection of rat islet xenografts / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effects of gene transfer cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) and anti-cluster of differentiation 154 (CD154) mAb on the rejection of rat islet xenografts.</p><p><b>METHODS</b>Human islets were infected with the recombinant adenoviruses containing CTLA4-Ig gene. Transduced islets were transplanted under the left kidney capsule of diabetic rats. And then the animal model were treated with anti-CD154 monoclonal antibody. The changes of blood sugar were measured and the survival rates of grafts and transplantation rats were observed after transplantation. The morphological changes of grafts were observed. Expression of CTLA4-Ig and insulin were detected by immunohistochemical staining and cytokines were quantified by ELISA.</p><p><b>RESULTS</b>(1) The blood glucose of transplantation rats decreased to normal level on 2nd day post-transplantation. The average level blood glucose of control group A, anti-CD154mAb treatment group B, transfected group C and associated treatment group D increased on day 8, 18, 25, 36, post-transplantation respectively. (2) The grafts of group A, B, C and D survived for (10.0 +/- 2.1) d, (22.0 +/- 8.2) d, (28.0 +/- 6.5) d and (37.0 +/- 9.3) d respectively. The survival of grafts in group D was significant longer than that in group A, B and C, respectively; The survival of group B and C were significantly prolonged compared with group A and the survival of group B was significantly different with group C (P < 0.05). The survival of transplantation rats were (21.0 +/- 5.7) d, (35.0 +/- 6.5) d, (48.0 +/- 8.5) d and (65.0 +/- 12.5) d in group A, B, C and D, respectively. The survival of transplantation rats compared each other among four groups were same as the survival of grafts (P < 0.05). (3) In control animals (group A), serum IL-2 and TNF-alpha concentration were elevated to a high level within seven days post-transplantation and significantly increased compared with that before transplantation (P < 0.01). (4) Hematoxylin-eosin staining of grafts showed a lot of islets under the kidney capsule of transplantation rats, no inflammatory cell infiltrate and immunohistochemical staining of grafts demonstrated expression of insulin protein at islets in group B, C and D. These grafts positively stained for CTLA4-Ig in group C and D.</p><p><b>CONCLUSIONS</b>Gene transfer CTLA4-Ig and anti-CD154mAb treatment can inhibit the rejection of rat islet xenografts and treatment Ad-CTLA4-Ig and anti-CD154 mAb could induce immune tolerance of islet xenografts.</p>