Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer / 中华肿瘤杂志

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

Impact of microplastics on children s health / 中国学校卫生

Abstract@#As a new type of pollutant, microplastics have attracted extensive attention. Children in a critical stage of growth and development are vulnerable to microplastics. Summarzing the relevant laws and regulations and the source of microplastics, the paper demonstrates the ways of microplastics entering human body, some toxic effects of microplastics found in recent experimental studies and their potential hazards to children s health are introduced in detail.

Analysis of etiological composition and changing trend of chronic kidney disease / 中华健康管理学杂志

Objective:To analyze the etiological composition and changing trends in chronic kidney disease.Methods:CKD patients from our hospital were in cluded in the study from three separate periods, 173 patients from 1990-1991, 956 patients from 2009-2010, and 1440 patients from 2018-2019. The etiology of CKD in patients between the younger and middle-aged group and the elderly group were compared using the χ2 test, and the Bonferroni method was used to correct the pairwise comparisons.Results:The leading cause of CKD in 1990-1991, 2009-2010, and 2018-2019 was chronic glomerulonephritis (52%), chronic glomerulonephritis (35%), and diabetes (36%), respectively. The distribution of the etiologies was different signficantly among the three cohorts (χ2=74.375, P<0.001). Compared with 1990-1991, the percentage of CKD related to diabetes (χ2=14.847, P=0.001) and hypertension (χ2=12.279, P=0.002) significantly increased, while chronic glomerulonephritis showed a downward trend (χ2=19.976, P<0.001). Among the elderly CKD patients, the leading cause of CKD in the three cohorts was chronic glomerulonephritis (34%), diabetes (40%), and diabetes (43%), respectively. Conversely, diabetes and hypertension have become the predominant causes in 2009-2010 and 2018-2019. Although chronic glomerulonephritis remained the leading cause of CKD in the past 30 years, the percentage declined gradually among the younger and middle-aged patients with CKD. The percentage of CKD related to diabetes (χ2=31.345, P<0.001) and hypertension (χ2=15.485, P<0.001) significantly increased. In addition, in the 2018-2019 cohort, there were 494 patients with end-stage renal disease (ESRD), and the percentage of ESRD related to diabetes and hypertension were 48% and 37%, respectively. Conclusion:Diabetes and hypertension have become the predominant causes of CKD in Chinese elderly patients. Although chronic glomerulonephritis was the leading cause among the younger and middle-aged patients with CKD, the percentage declined gradually. Additionally, diabetes and hypertension were also the predominant causes of ESRD.

Regulatory Effect of Huadu Sanyinfang on PI3K/Akt/NF-κB Pathway in Triple-negative Breast Cancer Patients with Qi-deficiency Constitution： An Exploration Based on Differential Expression of miRNA / 中国实验方剂学杂志

Objective:To explore the regulatory effect of Huadu Sanyinfang on phosphatidylinositol 3 kinase（PI3K）/protein kinase B（Akt）/transcription factor nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） in triple-negative breast cancer （TNBC） patients with qi-deficiency constitution based on the differential expression of miRNA. Method:Based on previous research results， this study conducted the bioinformatics analysis to predict the target genes responsible for regulating the differential expression of miRNA between patients with qi-deficiency constitution and those with moderate constitution， which were intersected with TNBC target genes. The resulting intersection targets were then subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and protein-protein interaction （PPI） network analysis to obtain the key pathways and target genes for differentially expressed miRNA in regulating TNBC. TNBC patients with Qi-deficiency constitution were treated with Huadu Sanyinfang for three years after they completed the standard Western medical treatment. The peripheral blood of the patients was sampled before and after medication for detecting gene expression in the key pathways. Result:The comparison between patients with Qi-deficiency constitution and those with moderate constitution revealed 49 differentially expressed miRNAs （16 up-regulated and 33 down-regulated）， which regulated 1 445 TNBC target genes. As demonstrated by PPI and KEGG pathway enrichment analysis， the key genes were mainly tumor protein p53 （TP53）， Akt1， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 3 （MAPK3）， vascular endothelial growth factor A （VEGRA）， and tumor necrosis factor （TNF）. The key pathways included PI3K/Akt， MAPK， and RAS signaling pathways. A total of 11 TNBC patients with qi-deficiency constitution were enrolled. Compared with the situations before treatment， the expression levels of p105 subunit of NF-κB （NF-<italic>κ</italic>B1） and Akt1 in the PI3K/Akt signaling pathway were down-regulated after medication， while the levels of catalytic subunit alpha of PI3K （PIK3CA） and B-cell lymphoma-xL （Bcl-xL） were up-regulated. The differences in NF-<italic>κ</italic>B1 and Akt1 expression were statistically significant. Conclusion:Huadu Sanyinfang is able to affect the gene expression of PI3K/Akt/NF-<italic>κ</italic>B signaling pathway in TNBC patients with Qi-deficiency constitution. Specifically， it down-regulates NF-<italic>κ</italic>B1 and Akt1 expression and up-regulates PIK3CA and Bcl-xL.

Influence of total femtosecond laser small incision lenticule extraction on corneal surface regularity index / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the influence of total femtosecond laser small incision lenticule extraction(SMILE)on corneal surface regularity index(SRI).<p>METHODS:Totally 210(401 eyes)myopic patients treated in Qinhuangdao Optometry Ophthalmology Hospital between January 2017 and December 2019 were enrolled in the study. Among them, patients treated with total femtosecond laser SMILE were included in the observation group(<i>n</i>=110, 205 eyes), while those treated with femtosecond laser-assisted <i>in situ</i> keratomileusis(FS-LASIK)were includded in the control group(<i>n</i>=100, 196 eyes). The uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), anterior corneal surface asphericity index(Q-value)at a diameter of 6mm and SRI were compared between the two groups before and after operation.<p>RESULTS: The UCVA and BCVA of both groups were improved at 3mo and 6mo after operation(<i>P</i><0.05), without significant differences between the groups(<i>P</i>>0.05). The observation group had higher SRI than the control group at 3mo, 6mo and 1a(<i>P</i><0.05). The asphericity parameter Q-values increased at each time point after operation. Besides, the observation group had lower Q-values than the control group at 6mo and 1a(<i>P</i><0.05).<p>CONCLUSION: Compared with FS-LASIK, SMILE can achieve similar visual recovery effect. However, the SRI is larger after SMILE, and the influence on asphericity index Q-value is less.

The Spectrum of Biopsy-Proven Glomerular Disease in China: A Systematic Review / 中华医学杂志(英文版)

<p><b>Background</b>Chronic kidney disease has become a leading public health concern in China, as it is associated with increased morbidity, mortality, and costs. However, the overall situation regarding common glomerular diseases in China remains unclear. Hence, the aim of this study was to assess the national profile of the common types of glomerulonephritis in China.</p><p><b>Methods</b>We searched Medline, Embase, Cochrane Library, CNKI, SinoMed, VIP, and Wanfang databases for English and Chinese language articles from inception to September 2017. We also collected potentially relevant studies and reviews using a manual search. The following words in combinations are as keywords: "renal biopsy", "kidney pathological diagnosis", and "spectrum of pathological types".</p><p><b>Results</b>We identified 23 studies involving 176,355 patients from 15 provinces/cities in China. The detection rates of primary glomerulonephritis (PGN) and secondary glomerulonephritis (SGN) were 0.740 and 0.221, respectively. Over the past 30 years, the top five types of PGN were immunoglobulin A nephropathy (IgAN; 24.3%), mesangial proliferative glomerulonephritis (MsPGN; 10.5%), membranous nephropathy (MN; 12.6%), minimal change disease (MCD; 9.8%), and focal segmental glomerulosclerosis (FSGS; 4.6%), and the top four types of SGN were lupus nephritis (LN; 8.6%), Henoch-Schönlein purpura glomerulonephritis (4.1%), hepatitis B virus-associated glomerulonephritis (HBV-GN; 2.6%), and diabetic nephropathy (DN; 1.6%). The proportion of MN, MCD, HBV-GN, and DN tended to increase, while those of IgAN, MsPGN, FSGS, and LN tended to drop.</p><p><b>Conclusions</b>Although the incidence of SGN is increasing gradually, PGN is still the leading form of kidney disease in patients undergoing renal biopsies in China. IgAN and LN are the most common types of PGN and SGN, respectively. Differences between regions are related to various factors such as nationality, environment, and diet. Furthermore, unified standards and norms for evaluating renal biopsies are urgently needed.</p>

Role of mature liver cells and oval cells in liver regeneration after liver injury / 中国组织工程研究

BACKGROUND: Retrorsine (RS) is a chemical agent for the long-term inhibition of mature liver cell division and proliferation. OBJECTIVE: To establish a rat model of liver injury by combined use of RS and 1/3 partial hepatectomy, to observe the proliferation of liver cells and oval cells in rats after liver injury, and to discuss the relationship between liver regeneration and mature liver cells and oval cells after liver injury. METHODS: Thirty male Sprague-Dawely rats were randomized into two groups (n=15 per group): RS group and control group. Rats in the RS group were subjected to intraperitoneal injection of RS, 30 mg/kg, twice in total, with 2 weeks in between; and rats in the control group were injected physiological saline instead of RS. Four weeks after the last injection, the 1/3 partial hepatectomy was performed in two groups of rats. Liver pathological and morphological changes as well as cell proliferation were observed, and CK19 and C-kit immunohistochemical detections of the rat liver in the two groups were conducted at different time points after operation. RESULTS AND CONCLUSION: At 20 days after operation, the body mass of the RS group rats was still lower than the baseline, and the liver increase was obviously less than that in the control group; there was cell body swelling shown by hematoxylin-eosin staining, loose cytoplasm, extensive vacuoles degeneration of liver cells, and clustered or scattered oval cells around the portal area of small bile duct and in the hepatic lobule. However, in the control group, the body mass was close to the baseline, liver damage was lighter than that in the RS group, a large number of mature liver cells proliferated under BrdU Immunofluorescence at 20 days after operation; liver oval cells proliferated and distributed in the liver cell line at 14 days after operation, with morphology and immunohistochemical markers consistent with oval cells in the RS group. These findings indicate that the rat model of acute liver injury is successfully established by combining retrorsine with 1/3 partial hepatectomy, liver poisoning and the proliferation of liver stem cells and mature liver cells after poisoning can be seen in the experiment, which firmly confirm that liver cell renewal and regeneration after injury is accredited to the combined action of liver stem cells in liver basin and mature liver cells.

Clinicopathology characteristics of idiopathic membranous nephropathy in elderly patients / 中华全科医师杂志

Objective To investigate the clinicopathological characteristics of idiopathic membranous nephropathy (IMN) in elderly patients.Methods Clinicopatholigical data of 400 patients with IMN identified by renal biopsy from January 2006 to December 2016 were analyzed retrospectively.The patients were divided into three groups:the young (≤44 years old),the middle-aged (45-59 years old) and the elderly (≥60 years old),and the clinicopathological characteristics were compared among three groups.Results The average age of the elderly group was (64.9 ± 4.3) years,the elderly group had worse renal function than the young group (F =784.60,P =0.000) and the middle-aged group [estimated glomerular filtration rate (eGFR) were (91.1 ± 25.9) 、(119.8 ± 37.0) and (102.5 ± 33.2) ml · min-1 · 1.73 m-2,F =21.74,P =0.000].The incidence of hypertension was higher in the elderly group than the other two groups [40.0％ (32/80) vs.19.6％ (30/153) and 22.2％ (37/167),x2 =12.76,P =0.003].The incidence of MN with ischemic nephropathy and tubulointerstitial lesion in the elderly group was higher than in the young group[15.0％ (12/80) vs.5.8％ (9/153),x2 =5.31,P =0.021].Conclusion The elderly patients with IMN are likely to be complicated with hypertension,ischemic nephropathy and tubulointerstitial lesions indicating poorer prognosis,so more attention should be paid to the early diagnosis and treatment of these comorbidities.

Topically applied hypericin exhibits skin penetrability on nude mice / 中国药理学与毒理学杂志

OBJECTIVE Hypericin, a powerful naturally photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of a topically applied hypericin, expecting reducing the risk of prolonged skin photosensitivity, which often occurs after systemic administration. METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers. In vivo studies, fluorescence microscopy was performed to examine the distribution of hypericin in the skin, macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin. RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mice skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treat?ment. CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.

A Sj(o)gren's syndrome patient with prominent aortic valve involvement: a case report / 北京大学学报(医学版)

Sj(o)gren's syndrome is a systemic autoimmune disease which is characterized by xerosis,and multiple organs can be affected,causing interstitial lung disease,renal tubular acidosis,blood system involvement,peripheral neuropathy,and liver damage,but cardiac involvement is rare.Here we report a case of Sj(o)gren's syndrome with prominent aortic valve involvement.A 66-year-old woman was admitted for exertional dyspnea,and the ultrasonic cardiogram showed severe aortic stenosis with moderate regurgitation.Preoperative examination for valve replacement found that the patient had elevated erythrocyte sedimentation rate and positive rheumatoid factor,so she was referred to the rheumatology outpatient department for further examination and treatment.Further questions about medical history found that the patient had dry eyes and dry mouth for more than ten years,and had obvious caries.Further laboratory examination showed elevated serum immunoglobulin levels and positive anti-nuclear antibody.The findings of ophthalmologic examination and labial gland biopsy also supported the diagnosis of Sj(o)gren's syndrome.After treatment of glucocorticoids and hydroxychloroquine for ten months,her dyspnea symptoms were obviously improved in the patient,and the rheumatoid factor had become negative while her erythrocyte sedimentation rate normal.Repeated ultrasonic cardiogram examination showed that her aortic stenosis was also improved.The patient has been followed up for four years,and her condition kept stable.Cardiac involvement in Sj(o)gren's syndrome can affect all parts of the heart,but valve involvement is relatively rare.The specific relationship between cardiac involvement and Sj(o)gren's syndrome and the mechanisms behind these associations both need further research.

Performance of the 2015 ACR/EULAR classification criteria compared with other classification criteria for diagnosis of gout in Chinese patients / 北京大学学报(医学版)

Objective:To evaluate the ability of 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria to diagnose gout compared with the widely used 1977 American Rheumatism Association (ARA) criteria and other criteria in clinical practice in Chinese patients,and to compare the sensitivity and specificity of different classification criteria for gout in early and established diseases.Methods:The patients who had ankle arthritis and visited the Department of Rheumatology and Clinical Immunology,Peking University First Hospital between February 2012 and February 2016 were screened.The patients who had been already diagnosed with gout or pyrophosphate deposition disease through arthrocentesis or tissue aspiration and those who had been diagnosed with rheumatoid arthritis,spondyloarthritis,and osteoarthritis were excluded.The patients were diagnosed by two experienced rheumatologists and all of them were followed up for at least one year.Early disease was defined as symptom onset of no more than 2 years;established disease was defined as symptom duration of more than 2 years.The 2015 ACR classification criteria were divided into clinical form with clinical parameters included and complete form with not only clinical parameters but also synovial fluids tests,imaging findings and monosodium urate (MSU) included.The two forms above were short for "clinical form (incorporating clinical parameters)" and "complete form (incorporating imaging and MSU data) " respectively.Results:In this study,284 patients suffering from ankle arthritis were included in the study,219 of them were classified as gout and 65 of them had alternative diagnoses.The sensitivity and specificity of 2015 ACR complete form (incorporating imaging and MSU data) for diagnosing gout were 88.13％ and 95.38％,respectively.The area under the curves (AUC) of 2015 ACR "complete form (incorporating imaging and MSU data)",2015 ACR "clinical form (incorporating clinical parameters) ",2010 Netherlands criteria and 1977 ARA criteria were 0.982,0.983,0.963,and 0.928,respectively.For the 94 early gout patients,the AUC of the above criteria were 0.973,0.968,0.916,and 0.910,respectively.For the established gout patients,the AUC were 0.987,0.991,0.982,and 0.936,respectively.For the patients with disease duration within two years,the odd ratio (OR) for sensitivity of 2015 ACR "complete form (incorporating imaging and MSU data)",2015 ACR "clinical form (incorporating clinical parameters)",2010 Netherlands criteria and 1977 ARA criteria were 1.562 (1.003-2.435),1.500 (1.001-2.346),and 1.812 (1.177-2.791),nevertheless,for the patients with established gout,the OR were 1.702 (1.300-2.229),1.607 (1.224-2.110),and 1.821 (1.396-2.377),respectively.Conclusion:The 2015 ACR/EULAR criteria are more accurate in gout diagnosis compared with the 1977 ARA criteria by elevating the sensitivity and specificity,in respective of the disease duration.The 2015 ACR/EULAR criteria may serve as new diagnostic tools in daily clinical practice in Chinese patients.

The gene polymorphisms of drug targets in Pneumocystis jiroveci isolates / 中华传染病杂志

Objective To investigate gene polymorphisms of drug targets and mutations associated with drug resistance in Pneumocystis jiroveci (P.jiroveci) isolates.Methods Among 148 samples isolated from human immunodeficiency virus (HIV)infected patients with pneumonia in Guangdong,mitochondrid larg subunit rRNA (mtLSUrRNA) gene was amplified from 51 samples.Dihydropteroate synthase (DHPS),dihydrofolate reductase (DHFR) and Cytochrome b (CYB) genes of P.jiroveci were detected by gene sequencing,and compared with the reference sequences in GenBank to evaluate gene polymorphisms.Results P.jirovecii DHPS,DHFR and CYB genes were all successfully amplified from 51 samples.For DHPS gene,48 (94.1％) were wild-type and 3 (5.9％) had gene mutation associated with drug resistance.For DHFR gene,30 were wild-type,and 21 had a synonymous mutation at position 312,and 1 nonsynonymous mutation at position 188.There were no mutations associated with drug resistance.For CYB gene,polymorphisms of were detected at 5 sites,4 of which were synonymous mutations,1 was non-synonymous mutation.No mutation associated with drug resistance was found.Based on the gene polymorphism of CYB6,the strains can be classified into 6 genotypes,and 2 were first detected,including 25 CYB1,13 CYB2,2 CYB5,4 CYB8,as well as newly detected 4 CYB10 and 3 CYB11 strains.Conclusions The mutations associated with drug resistance in P.jiroveci isolates in Guangdong remain uncommon.CYB gene shows gene polymorphisms and can be selected as one of targeted genes for multilocus sequence typing.

Pregnane receptor gene polymorphisms, pathogenic bacteria distribution and drug sensitivity, and TCM syndrome differentiation in patients with cholelithiasis

OBJECTIVE@#To investigate the distribution of pathogens and drug resistance in bile and the association between the pregnane X receptor (PXR) gene polymorphisms, traditional Chinese medicine (TCM) syndromes and the risk of cholesterol gallstone disease (CGD).@*METHODS@#A total of 392 samples were enrolled in this study from January 2014 to February 2015, among which 192 patients were with CGD, and 200 samples were healthy. Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing. The patients were divided into hepatochlic hygropyrexia, stagnation of liver-qi, and the accumulation of damp. The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis.@*RESULTS@#A total of 192 cases were detected in 230 of bile culture pathogens, including Gram-negative bacteria 133 (57.83%), Gram-positive bacteria 76 (33.04%), and fungi 21 (9.13%). The top five pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Candida albicans, and Enterococcus feces, of which 110 cases was of single infection, 48 cases of mixed infection of two strains, eight cases of mixed infection of three bacteria. Among 59 Escherichia coli, the yield extended-spectrum beta-lactamases had 40 (67.80%). The hepatochlic hygropyrexia was the most TCM syndrome, followed by stagnation of liver-qi, and the accumulation of damp was least. Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes (P < 0.05). In hepatochlic hygropyrexia patients the Gram-negative bacteria was most. There was significant differences between CGD group and control group in rs6785049 (P < 0.001). Comparison with wild-type portable GG, GA genotype increased the risk of the occurrence of gallstones (OR = 0.40, 95%CI: 0.16-0.79); likewise, carrying the GA+AA genotype also increased the risk (OR = 0.38, 95%CI: 0.19-0.81). There was no significant differences in rs2276707, rs3814055 site polymorphic loci alleles in CGD group and control group.@*CONCLUSIONS@#In the treatment of cholelithiasis, bile samples should be collected for bacterial culture and sensitivity test, and drugs should be strictly chosen based on the results. The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny, and gallstones can be early detected and prevented by detecting genotypes. rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.

Effects of retinol on expressions of epidermal growth factor, stem cell factor, colony-stimulating factor 1 and leukemia inhibitory factor in human umbilical cord-derived mesenchymal stem cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate effects of retinol on the expressions of epidermal growth factor (EGF), stem cell factor (SCF), colony-stimulating factor 1 (CSF1) and leukemia inhibitory factor (LIF) in cultured human umbilical-derived mesenchymal stem cells (UCMSCs).</p><p><b>METHODS</b>Human UCMSCs were isolated from human umbilical cord and identified for immunophenotypes. The cells were then cultured in DMEM/F12 media supplemented with 12% fetal bovine serum (FBS), 12% FBS+1 µmol/L retinol, 15% knockout serum replacement (KSR) and 15% KSR+ 1 µmol/L retinol. The expressions of the cytokines EGF, SCF, CSF1 and LIF in the cells were detected using RT-PCR and ELISA.</p><p><b>RESULTS</b>The isolated cells exhibited characteristic immunophenotypes of human UCMSCs and expressed EGF, CSF1 and SCF at both mRNA and protein levels but not LIF protein. Retinol (1 µmol/L) significantly promoted the expressions of SCF and CSF1 at both mRNA and protein levels but did not result in changes of EGF and LIF expressions in human UCMSCs.</p><p><b>CONCLUSION</b>Retinol at the concentration of 1 µmol/L can promote expression of SCF and CSF1 in human UCMSCs in vitro.</p>

Pregnane receptor gene polymorphisms, pathogenic bacteria distribution and drug sensitivity, and TCM syndrome differentiation in patients with cholelithiasis

Objective: To investigate the distribution of pathogens and drug resistance in bile and the association between the pregnane X receptor (PXR) gene polymorphisms, traditional Chinese medicine (TCM) syndromes and the risk of cholesterol gallstone disease (CGD). Methods: A total of 392 samples were enrolled in this study from January 2014 to February 2015, among which 192 patients were with CGD, and 200 samples were healthy. Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing. The patients were divided into hepatochlic hygropyrexia, stagnation of liver-qi, and the accumulation of damp. The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis. Results: A total of 192 cases were detected in 230 of bile culture pathogens, including Gram-negative bacteria 133 (57.83%), Gram-positive bacteria 76 (33.04%), and fungi 21 (9.13%). The top five pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Candida albicans, and Enterococcus feces, of which 110 cases was of single infection, 48 cases of mixed infection of two strains, eight cases of mixed infection of three bacteria. Among 59 Escherichia coli, the yield extended-spectrum beta-lactamases had 40 (67.80%). The hepatochlic hygropyrexia was the most TCM syndrome, followed by stagnation of liver-qi, and the accumulation of damp was least. Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes (P < 0.05). In hepatochlic hygropyrexia patients the Gram-negative bacteria was most. There was significant differences between CGD group and control group in rs6785049 (P < 0.001). Comparison with wild-type portable GG, GA genotype increased the risk of the occurrence of gallstones (OR = 0.40, 95%CI: 0.16-0.79); likewise, carrying the GA+AA genotype also increased the risk (OR = 0.38, 95%CI: 0.19-0.81). There was no significant differences in rs2276707, rs3814055 site polymorphic loci alleles in CGD group and control group. Conclusions: In the treatment of cholelithiasis, bile samples should be collected for bacterial culture and sensitivity test, and drugs should be strictly chosen based on the results. The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny, and gallstones can be early detected and prevented by detecting genotypes. rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.

Diastolic function and new-onset atrial fibrillation following cardiac surgery.

Background: Numerous studies have reported predictors of new‑onset postoperative atrial fibrillation (POAF) following cardiac surgery, which is associated with increased length of stay, cost of care, morbidity, and mortality. The purpose of this study was to examine the association between preoperative diastolic function and occurrence of new‑onset POAF in patients undergoing a variety of cardiac surgeries at a single institution. Methods: Using data from a prospective study from November 2007 to January 2010, a retrospective review was conducted. The diastolic function of each patient was determined from preoperative transthoracic echocardiograms. Occurrence of new‑onset POAF was prospectively noted for each patient in the original study. Demographic and operative characteristics of the study population were analyzed to determine predictors of POAF. Results: Of 223 patients, 91 (40.8%) experienced new‑onset POAF. Univariate predictors of POAF included increasing age, male gender, operations involving mitral valve repair/replacement, nonsmoking, hypertension, increased intraoperative pulmonary artery pressure, grade I diastolic dysfunction, abnormal diastolic function of any grade, decreased medial e’, elevated medial E/e’, and increased left atrial volume. Multivariate predictors of POAF included increasing age, increased left atrial volume, and elevated initial intraoperative pulmonary artery pressure. Even after exclusion of patients with hypertrophic obstructive cardiomyopathy or those undergoing mitral valve operations, diastolic dysfunction was not a multivariate predictor of POAF. Conclusions: In the patient population studied here, preoperative diastolic dysfunction was not predictive of POAF. In addition to increasing age, initial intraoperative pulmonary artery systolic pressure and left atrial volume were both significant multivariate predictors of POAF.

The clinical value of plasma M type phospholipase A2 receptor antibody and IgG subtypes deposition in diagnosis of hepatitis B virus-associated membranous nephropathy / 国际检验医学杂志

Objective To investigate the different expressions of plasma M type phospholipase A2 receptor antibody and IgG subtypes deposition of kidney tissues in idiopathic membranous nephropathy and hepatitis B virus-associated membranous nephropa-thy,and to evaluate the significance of plasma M type phospholipase A2 receptor antibody and IgG subtypes in diagnosis of hepatitis B virus-associated membranous nephropathy.Methods Plasma samples were obtained from patients with idiopathic membranous nephropathy,hepatitis B virus-associated membranous nephropathy and minimal change disease,respectively,before immunosup-pressive therapy.Concentration of plasma M type phospholipase A2 receptor antibody was detected by sandwich ELISA and concen-tration of IgG subtypes were measured by immunofluorescence.Results Concentration of plasma M type phospholipase A2 receptor antibody was (15.4±7.2)μg/mL in idiopathic membranous nephropathy group,higher than that in the hepatitis B virus-associated membranous nephropathy group (10.3±5.7)μg/mL (P <0.01),between idiopathic membranous nephropathy group and hepatitis B virus-associated membranous nephropathy group.There was no distinct difference of IgG subtypes deposition in glomerlar capil-lary wall.Conclusion There is obvious clinical significance of concentration of plasma M type phospholipase A2 receptor antibody in differential diagnosis of idiopathic membranous nephropathy and hepatitis B virus-associated membranous nephropathy,while no distinct significance of IgG subtypes deposition.

The effect and mechanism of curcumin derivative B06 on the myocardium from type 2 diabetic rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effect and mechanism of curcumin derivatives B06 on myocardium from type 2 diabetic rats.</p><p><b>METHODS</b>Thirty-five male SD rats were randomly divided into 5 groups, normal control group (NC group), high fat group (HF group), high fat treatment group (FT group), diabetes mellitus group (DM group) and diabetes treatment group (DT group) (n = 7). The late four groups were fed with high fat food, after four weeks of high fat feeding, the rats from DM group and DT group were injected with low dosage of streptozocin intraperitoneally to induce diabetes mellitus, FT group and DT group were gavaged with curcumin derivatives B06 at the dosage of 0.2 mg/kg x d. The blood glucose and lipid were detected biochemically, blood insulin was assayed by ELISA and the insulin resistance index was calculated, the morphology of myocardium was observed by light and transmission electron microscopy, the protein expression of AMP-activated protein kinase alpha (AMPKalpha) and phosphorylated AMP-activated protein kinase alpha (p-AMPKalpha) in myocardium were tested by Western blot.</p><p><b>RESULTS</b>The level of blood glucose, lipid, insulin and the insulin resistance index were increased in HF group and DM group, but they were decreased after the treatment with B06. The expression of AMPKalpha and p-AMPKalpha were decreased, but they became increased after the treatment of B06. There were increased collagen fibers in interstitium and expansion of mitochondria in cytoplasm of myocardium from DM group, but they were ameliorated in B06 treatment group.</p><p><b>CONCLUSION</b>It is suggested that B06 may relieve the damage of myocardium from type 2 diabetic rats and the increased expression of AMPKalpha and p-AMPKalpha may be involved in it.</p>

Effects of TIMP-1 on PTEN expression on renal tubular epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in regulating both angiogenesis and the expressions of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and vascular endothelial growth factor (VEGF)/Flk-1 expression in human proximal tubular epithelial cells (HKC).</p><p><b>METHODS</b>HKC cells were transfected with two recombinant plasmids containing sense and antisense full-length TIMP-1 cDNA (TIMP-1S-pcDNA3.0 and TIMP-1AS-pcDNA3.0, respectively) constructed previously, or treated with 100 µmol/L MMP-2/MMP-9 inhibitor III (with similar cellular enzyme suppression activity with sense TIMP-1 plasmid). The mRNA expression of TIMP-1, MMP-2, MMP-9, PTEN, VEGF and Flk-1 were examined by RT-PCR. In each group, the expression of PTEN, VEGF and Flk-1 were also detected using an indirect immunofluorescence assay.</p><p><b>RESULTS</b>Compared with non-transfected cells and cells transfected with the empty vector, sense TIMP-1-transfected cells showed obviously upregulated PTEN expression (P<0.05) and significantly lowered gelatinase activity (P<0.05) and VEGF and Flk-1 expressions (P<0.05). Transfection with the antisense TIMP-1 plasmid produced the reverse results (P<0.05). MMP-2/MMP-9 inhibitor III did not obviously affected the expression of PTEN, VEGF or Flk-1 as compared with the non-transfected or empty vector-transfected cells.</p><p><b>CONCLUSION</b>In the aging progress, the renal tissues express high levels of TIMP-1 to upregulate PTEN expression via a MMP-independent pathway, and subsequently down-regulates the expression of VEGF and Flk-1 to cause aging-related impairment of renal angiogenesis. These findings provide new evidence for understanding the role of TIMP-1 in renal aging.</p>

Study on reproductive toxicity in male embryo rats with the pregnancy SD rates exposed by nonylphenol / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of nonylphenol (NP) exposure on the genital development of fetal male rats in pregnant rats, and to measure the mRNA and protein expression of insulin-like factor3 (Insl-3) in the testicular tissue of fetal rats.</p><p><b>METHODS</b>A total of 100 pregnant SD rats were equally assigned to blank control group and four NP treated groups. Each rat in the NP treated groups received intragastric administration of NP at doses of 5, 40, 100, or 200 mg/kg/d from day 14 to 19 of gestation, and the rats in the blank control group received intragastric administration of pure peanut oil. The pregnant rats were sacrificed on day 19 of gestation. The body weight and testicular weight of each fetal rat were measured, and the descent of testis was also observed. The mRNA and protein expression of Insl-3 in the testicular tissue of fetal rats was analyzed by reverse transcription-PCR and Western blot.</p><p><b>RESULTS</b>Compared with the blank control group, the 40, 100, and 200 mg/kg NP treated groups showed significantly decreased body weight and weight coefficient of testis (P < 0.05 or P < 0.01), significantly decreased testicular descent (P < 0.05), and significantly decreased mRNA and protein expression of Insl-3 (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Exposure to nonylphenol can lead to testicular maldevelopment, incomplete testicular descent, and Insl-3 expression downregulation of fetal male rats in pregnant rats.</p>