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To investigate the efficacy and value of optical genome mapping (OGM) in detecting chromosomal structural variations. In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases, a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology, and Endocrinology of Peking Union Medical College Hospital from January to December 2021. Ten cases with abnormal karyotype was detected by OGM. Partial cases were verified by fluorescence in situ hybridization (FISH), SNP array or CNV-seq. Results of ten cases, nine were detected with abnormality by OGM, including unbalanced chromosomal rearrangements (n=3), translocation (n=5) and paracentric inversion (n=1), and the results were in concordance with other standard assays. However, one case with breakpoint and reconnected at centromere has not been detected. In conclusion, ten samples were comprehensively analyzed by karyotyping, FISH, SNP array or CNV-seq, and OGM, and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions, but more importantly, it can refine breakpoints and orientation of duplicated segments or insertions. So it can contribute to the diagnosis of genetic diseases and prevent birth defect. However, the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.
Subject(s)
Female , Humans , Pregnancy , Chromosome Mapping , In Situ Hybridization, Fluorescence , Karyotyping , Retrospective Studies , Translocation, GeneticABSTRACT
Severe hyperthyroidism can cause the injuries of multiple organs including heart and liver and ultimately be fatal. A 26-year-old young woman admitted to Peking Union Medical College Hospital for severe hyperthyroidism due to irregular use of anti-thyroid drugs. She had heart failure,atrial fibrillation,and severe liver damage at admission. Anti-thyroid drugs were then actively used to treat the primary disease,along with interventions to correct heart failure and control atrial fibrillation. Severe total bilirubin elevation was found during the treatment, which was resolved after the use of glucocorticoid and liver-protective therapy. The patient was regularly followed up after discharge,and the clinical manifestations were good.
Subject(s)
Adult , Female , Humans , Atrial Fibrillation , Heart Failure , Hyperthyroidism , Liver DiseasesABSTRACT
Objective To investigate the effects of metformin on insulin sensitivity and secretion in patients with obesity and insulin resistance. Methods This study enrolled 42 obesity patients with insulin resistance who were regularly followed-up in Peking Union Medical College Hospital from September 2012 to May 2016. They were divided into two groups according to their different status of glucose metabolism: normal glucose tolerance( NGT) and impaired glucose regulation( IGR) . Life style intervention and metformin were given to all these patients. The antropometric and metabolic data were collected before treatment, 3 and 6 months after treatment respectively. Results 42 patients, aged (23.6±6.5) years, including 11 males and 31 females were enrolled. 19 of them were NGT and 23 were IGR (8 of IGT and 15 of IFG) . Among all these patients, fasting insulin was significantly higher at 3 months after treatment(P＜0.05).The same results were shown in group-NGT(P＜0.05). Fasting insulin was significantly lower at 6 months after treatment than at baseline among all patients( P＜0.05) . HOMA-IR showed no significant difference between the baseline and 3 months after treatment, but significantly higher at baseline and 3 months after treatment than 6 months after therapy( P＜0.001) . HOMA-beta was significantly( P＜0.001) lower be-fore treatment and 6 months treatment the effect was more significant than 3 months after treatment among all pa-tients. HOMA-beta was significantly lower at baseline in group-IGR than at baseline in group-NGT ( P＜0.05) . Conclusions The effect of metformin on insulin secretion is earlier than that of improving the insulin sensitivity in patients with obesity and insulin resistance. Metformin is more likely to promote insulin secretion in patients with normal glucose tolerance than those with IGR within 3 months of intervention.
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Recombinant human growth hormone(rhGH)treatment can improve serum glycolipid metabolism,body composition and quality of life in adults growth hormone deficiency(AGHD).Individual differences in rhGH dose and rhGH response to treatment between different patients,gene polymorphisms may play an important role.
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Objective To observe the protein expression patterns of matrix metalloproteinase (MMP)-2 and MMP-9 in the liver tissue of liver contusion rats at different time after impact. Methods Fifty healthy adult male SD rats were randomly and evenly divided into control group and experimental groups (1 h, 3 h, 6 h, 12 h, 18 h, 24 h, 3 d, 5 d, 7 d after liver contusion). A rat liver contusion model was established by a free-falling device. The rats were killed at corresponding time, and the contused hepatic lobes were extracted. The protein expressions of MMP-2 and MMP-9 in contused liver tissue of the rats in each group were observed by immunohistochemical staining (SP method) and Western blotting. Results After the liver contusion, the expression of positive cell and the protein semiquantitative result showed that the protein expression of MMP-2 enhanced at 6 h and peaked at 24 h, then decreased gradually at 3-5 d, and returned to normal levels at 7 d. The difference of expression between group and its previous adjacent group after 6 h (except 18 h) had statistical significance (P<0.05). The protein expression of MMP-9 rose obviously at 1 h after liver contusion and peaked at 18 h, then decreased gradually at 3-7 d which still higher than control group. The expression difference between group and its previous adjacent group (except 12 h and 24 h) had statistical significance (P<0.05). Conclusion The protein expressions of MMP-2 and MMP-9 in contused liver tissue after impact show good time-dependent patterns, which may provide important reference indicators for the time estimation of liver contusion.
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<strong>Objective</strong> To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency (AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.<strong>Methods</strong> A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital, a major teaching hospital in Chinese Academy of Medical Sciences. Data of physicians' educational background, clinical training, patient workload per year and continuing medical education in AGHD were collected. Factors associated with appropriate answers were further analyzed by multivariate regression models.<strong>Results</strong> One hundred and eighteen internal medicine residents, endocrine fellows, attending physicians and visiting physicians responded to the survey. Among them, 44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy. Moreover, 56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD. Logistic regression analysis of physician demographic data, educational background, and work experience found no consistent independent factors associated with better decision-making, other than continued medical education, that were associated with treatment choice.<strong>Conclusions</strong> The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence. High quality continued medical education is required to improve Chinese physician management of AGHD.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Education, Medical, Continuing , Health Knowledge, Attitudes, Practice , Hormone Replacement Therapy , Human Growth Hormone , Logistic ModelsABSTRACT
Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency (AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital, a major teaching hospital in Chinese Academy of Medical Sciences. Data of physicians' educational background, clinical training, patient workload per year and continuing medical education in AGHD were collected. Factors associated with appropriate answers were further analyzed by multivariate regression models.Results One hundred and eighteen internal medicine residents, endocrine fellows, attending physicians and visiting physicians responded to the survey. Among them, 44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy. Moreover, 56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD. Logistic regression analysis of physician demographic data, educational background, and work experience found no consistent independent factors associated with better decision-making, other than continued medical education, that were associated with treatment choice.Conclusions The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence. High quality continued medical education is required to improve Chinese physician management of AGHD.
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<p><b>OBJECTIVE</b>To evaluate the clinical and angiographic outcomes of vasospastic angina patients with severe organic stenosis treated by drug-eluting stents.</p><p><b>METHODS</b>Between January 2006 and December 2010, severe organic stenosis (diameter stenosis more than 70%) was evidenced in 7 out of 46 vasospastic angina patients and treated with drug-eluting stents. Coronary angiography was repeated at 6 - 18 months after percutaneous coronary intervention and the patients were clinically followed up. The clinical and angiographic outcomes were observed.</p><p><b>RESULTS</b>Nine drug-eluting stents [mean diameter 2.75 - 3.50 (3.08 ± 0.24) mm, length 24 - 33 (27.3 ± 3.6) mm] were successfully implanted in these 7 patients. Stents were implanted into left anterior descending artery (LAD) in 5 patients (71.4%), right coronary artery (RCA) in 1 patient (14.3%), both LAD and RCA in 1 patient (14.3%). Transient RCA spasm and distal LAD spasm were observed during percutaneous coronary intervention of LAD in 2 patients. Anginal attack at rest with transient ST segment elevation at V(1)-V(3) leads occurred 24 hours after LAD stenting in 1 patient. Follow-up coronary angiography showed significant in-stent restenosis or focal edge restenosis (diameter stenosis more than 50%) in 3 patients (42.9%), mild neointimal proliferation but without significant restenosis in 2 patients (28.6%), and no neointimal proliferation in 2 patients (28.6%). During clinical follow-up of 17 to 50 months after percutaneous coronary intervention, 2 patients (28.6%) remained asymptomatic, while effort angina and/or rest angina was documented in the remaining 5 patients (71.4%).</p><p><b>CONCLUSIONS</b>Our results from this small patient cohort suggest that drug eluting stent implantation for severe organic stenosis in patients with vasospastic angina is linked with high incidence of restenosis and recurrent chest pain. Further observation in larger patient cohort is warranted to clarify the efficacy of this strategy for treating vasospastic angina patients with severe organic stenosis.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Angina, Unstable , Therapeutics , Angioplasty, Balloon, Coronary , Coronary Stenosis , Therapeutics , Drug-Eluting Stents , Treatment OutcomeABSTRACT
<p><b>BACKGROUND</b>Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited disease, which is a disorder with multiple organ involvement, mainly the kidney and liver. It is caused by mutations in the PKHD1 gene. Here, we reported the clinical characteristics of a case with ARPKD and analyze the genetic features of this patient as well as of his father using targeted exome sequencing and Sanger sequencing.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes obtained from a patient with ARPKD. The mutations were identified using exome sequencing and confirmed by Sanger sequencing.</p><p><b>RESULTS</b>The patient was diagnosed as ARPKD based on ultrasonography and abdominal computed tomography which showed polycystic changes, multiple calcinosis of both kidneys, and multiple dilated bile ducts of the liver. Compound heterozygous PKHD1 gene mutations A979G and G5935A, which lead to substitution of an asparagine for an aspartate at amino acid 327 (N327D) and a glycine for an arginine at amino acid 1979 (G1979R) respectively, were identified using targeted exome sequencing and confirmed by Sanger sequencing for the patient. In addition, the father of the patient was identified to be a carrier of heterozygous A979G mutation of this gene.</p><p><b>CONCLUSIONS</b>We identified that the compound heterozygous PKHD1 gene mutations are the molecular basis of the patient with ARPKD. Targeted exome sequencing is suitable for genetic diagnosis of single-gene inherited diseases like ARPKD in which the pathogenic gene is a large.</p>
Subject(s)
Adolescent , Humans , Male , Exome , Genetics , Genetic Predisposition to Disease , Mutation , Polycystic Kidney, Autosomal Recessive , Genetics , Receptors, Cell Surface , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To assess the prevalence of anti-alpha-enolase antibody in systemic autoimmune diseases in Chinese patients and its role in endothelial cell apoptosis.</p><p><b>METHODS</b>The reactivity of anti-alpha-enolase antibody in a variety of autoimmune disorders in Chinese patients was evaluated by dot blot assay. Endothelial cell apoptosis was investigated by in vitro incubation of endothelial cells with IgG purified from anti-alpha-enolase antibody-positive sera, with or without pre-incubation with recombinant alpha-enolase.</p><p><b>RESULTS</b>Anti-alpha-enolase antibody was prevalent in different systemic autoimmune diseases with relatively high reactivity in Chinese patients. In vitro incubation of endothelial cells with IgG containing anti-alpha-enolase antibody induced apoptosis in a time- and dose-dependent manner. Apoptosis was partly inhibited by pre-incubation of the endothelial cells with recombinant alpha-enolase.</p><p><b>CONCLUSIONS</b>Our data suggest that alpha-enolase is a common auto-antigen recognized by anti-endothelial cell antibodies in connective tissue disease. Interaction between alpha-enolase and its autoantibody plays a role in endothelial cell apoptosis. Changes other than cell killing may contribute to the pathogenesis of endothelial damage and microvascular lesions.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Apoptosis , Autoantibodies , Allergy and Immunology , Pharmacology , Autoimmune Diseases , Allergy and Immunology , Blotting, Western , Cell Line , Endothelial Cells , Cell Biology , Flow Cytometry , Immunoblotting , Phosphopyruvate Hydratase , Allergy and Immunology , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effects of Zuojin Pill and Fanzuojin Pill (ZJP and FZJP) on the growth metabolism of enterobacteria from the biothermodynamic viewpoint, and to objectively validate the difference between the two drugs for investigating a new way in congener Chinese drugs research.</p><p><b>METHODS</b>The growth metabolism power-time curves of enterobacteria affected by ZJP and FZJP in different concentrations were obtained by microcalorimetry. And the activities of the two drugs were assessed depending some related characteristic parameters, including growth rate constant (k), maximum output power (P(max)), peak time (T(p)) , maximum heat-output (Q1), and bacteria inhibition rate (I).</p><p><b>RESULTS</b>With the drugs' concentration increasing, T(p) was prolonged, k value reduced in enterobacteria, i.e. , the two drugs both inhibited the growth of enterobacteria in different extents. Comparison of inhibiting rates showed that the bacteriostasis activity of ZJP was greater than that of FZJP.</p><p><b>CONCLUSIONS</b>There was objective difference in activities of inhibiting enterobacteria between ZJP and FZJP. Microcalorimetry could express the features at real-time, on-line and sensitively. It was able to determine the activity of drugs accurately and quickly in appraising congener Chinese drugs, like ZJP and FZJP, by microcalorimetry.</p>
Subject(s)
Animals , Male , Mice , Calorimetry , Drugs, Chinese Herbal , Pharmacology , Enterobacteriaceae , Mice, Inbred StrainsABSTRACT
<p><b>OBJECTIVE</b>To explore the complex prescription compatibility law of the cold and hot nature of Mahuang Decoction (, MHD) and Maxing Shigan Decoction (, MXSGD), both categorized both categorized MHD) and Maxing Shigan Decoction (both categorized MXSGD), both categorized formulas but with different hot/cold natures.</p><p><b>METHODS</b>Oxygen consumption of mice was determined among three groups: MHD, MXSGD and the control; a cold-hot pad differentiating assay was used to observe the variability of temperature tropism among the groups of mice which was treated with MHD, MXSGD, and their compositions. Meanwhile, the total anti-oxidant capability (T-AOC) activity were detected.</p><p><b>RESULTS</b>After administration of MHD, the mice showed increased oxygen consumption (P<0.01). Compared with MHD group, the remaining rate of MXSGD mice on the hot pad was found to be significantly increased with the cold-hot pad differentiating assay (P<0.05). There was no significant difference (P>0.05) among the remaining rates of MXSGD, MXSGD with high dose Gypsum Fibrosum (MXHGF) group, and MXSGD with low dose Gypsum Fibrosum (MXLGF) group mice. Compared with the MHD group, T-AOC activity of the mice in the Consensus Compositons group was significantly decreased (P=0.0494). Compared with the MXSGD group, T-AOC activity of Gypsum Fibrosum (GF) group was increased significantly (P=0.0013).</p><p><b>CONCLUSIONS</b>The differences in cold and hot nature could be represented objectively between MHD with a hot nature and MXSGD with a cold nature. The reason may be the Gypsum Fibrosum which decreased the efficacy of the consensus compositions. However, increasing or decreasing the dose of Gypsum Fibrosum will not change the cold and hot nature of MXSGD.</p>
Subject(s)
Animals , Male , Mice , Cold Temperature , Hot Temperature , Medicine, Chinese Traditional , Oxygen ConsumptionABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of zinc-alpha2-glycoprotein (ZAG) on body weight and body fat in high-fat-diet (HFD)-induced obesity in mice and the possible mechanism.</p><p><b>METHODS</b>Thirty-six male mice were fed with standard food (SF) (n = 9) and HFD (n = 27), respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase (FAS) and hormone-sensitive lipase (HSL) in liver tissue were determined by reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice (0.51 +/- 0.10 AU vs. 0.75 +/- 0.07 AU, P < 0.01). Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r = -0.56, P < 0.001), epididymal fat mass (r = -0.67, P < 0.001), percentage of epididymal fat (r = -0.65, P < 0.001), and increased weight (r = -0.57, P < 0.001) in simple SF- and HFD-fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididymal fat. Furthermore, FAS mRNA expression decreased (P < 0.01) and HSL mRNA expression increased (P < 0.001) in the liver in ZAG over-expressing mice.</p><p><b>CONCLUSIONS</b>ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.</p>
Subject(s)
Animals , Male , Mice , Adipose Tissue , Metabolism , Fatty Acid Synthases , Genetics , Physiology , Liver , Mice, Obese , Seminal Plasma Proteins , Blood , Physiology , Sterol Esterase , Genetics , Physiology , Weight LossABSTRACT
This study is to investigate the authenticity between COLD and HOT natural attribute in the famous Chinese medicine formulas--Zuojinwan (Coptis-Evodia 6 : 1) and Fanzuojinwan (Coptis-Evodia 1 : 6) based on mice temperature tropism, and establish an objective method to estimate the difference of two natural attribute by using a cold/hot plate differentiating technology. The results indicated that the COLD nature Zuojinwan could decrease significantly the remaining rate of HOT-symptom rat on warm pad (P < 0.05). That was not notable to COLD-symptom rat. The interference result of COLD-HOT temperature tropism to COLD/HOT symptom rat in Fanzuojinwan was the reverse with the COLD nature Zuojinwan. Meanwhile, biochemical indicators which are relative to energy metabolism such as ATPase enzyme activity and total anti-oxidant capability (T-AOC), had corresponding change in the organism. In the study, the COLD and HOT natural tendency in Zuojinwan and Fanzuojinwan which were composed by the same herbs with different proportion could be expressed qualitatively, quantitatively, objectively and directly with applying animal temperature tropism, and be verified to philosophical idea of treating disease theory with "expelling heat with cold herbs and cryopathy requiring warm prescription", not "expelling heat with heat herbs and cryopathy requiring cold prescription" in ancient traditional Chinese medicine, which brings a new approach in investigation of the nature theory of traditional Chinese medicine.
Subject(s)
Animals , Male , Mice , Antioxidants , Pharmacology , Body Temperature , Body Weight , Ca(2+) Mg(2+)-ATPase , Metabolism , Calcium-Transporting ATPases , Metabolism , Cold Temperature , Coptis , Chemistry , Drugs, Chinese Herbal , Pharmacology , Evodia , Chemistry , Hot Temperature , Liver , Medicine, Chinese Traditional , Sodium-Potassium-Exchanging ATPase , Metabolism , TropismABSTRACT
OBJECTIVE@#To detect the concentrations of interleukin-18 (IL-18) and prostaglandin E2(PGE2) in synovial fluid (SF), and to determine the role of IL-18 and PGE2 in osteoarthritis (OA) pathogenesis.@*METHODS@#IL-18 and PGE2 were measured concurrently in synovial fluid samples from 54 patients with knee OA (OA group) and from 9 controls (control group). Quantitative determination of IL-18 was performed by enzyme-linked immunosorbent assay (ELISA). PGE2 was examined by inhibitory enzyme-linked immunosorbent assay. A linear regression between IL-18 and PGE2 was analysed.@*RESULTS@#The concentrations of IL-18 and PGE2 in SF from the OA group were significantly higher than those from the control group (P<0.01). The average value of IL-18 in the control group was (28.768+/-13.575) x 10(-9)ng/L, and (72.303+/-40.130) x 10(-9)ng/L in the OA group (P<0.01); the average value of PGE2 in the control group was (24.697+/-7.814) x 10(-9)ng/L, and (42.302+/-23.818) x 10(-9)ng/L in the OA group (P<0.01). IL-18 was related with PGE2 in a linear curve fashion (the control group: r=0.76, P<0.001; the OA group: r=0.94, P<0.001).@*CONCLUSION@#IL-18 and PGE2 are significantly higher in the OA group than those in the control group, and they might take part in the cartilage degradation in OA pathogenesis. The increase of IL-18 might induce the increase of PGE2, and that might play an important role in OA pathogenesis.