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Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×104, and the effective concentration of the positive drug was 1-100 µmol·L-1. In addition, pretreated with 10 µmol·L-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.
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AIM: To observe the changes of disease spectrum and characteristics of orbital disease distribution in orbital outpatients, introduce the procedures and methods of diagnosis and treatment of orbital diseases in our hospital and define the work focus and social needs in orbital disease. METHODS: Prospective observational study. A registration form was designed to record the gender, age and diagnosis of orbital outpatients in our treatment group. The orbital diseases were divided into seven categories for statistical analysis. The composition ratio, male to female ratio, age of onset, subtypes of dominant diseases and the top three common diseases were analyzed. This paper introduces the diagnosis and treatment process of the orbital disease specialty clinic of our hospital.RESULTS: A total of 1 059 patients with orbital diseases were registered from April 1 to December 31, 2021. The most common orbital diseases were thyroid-related ophthalmopathy(TAO)in 325 cases(30.7%), followed by orbital tumors in 282 cases(26.6%), orbital trauma in 213 cases(20.1%), orbital inflammation in 205 cases(19.4%). Orbital vascular malformation, congenital and genetic venereal diseases and other orbital diseases were 34 cases(3.2%). Pathological diagnosis: orbital tumors in 150 cases(72.8%)were benign, the first three benign tumors were hemolymphangioma, orbital cyst and neurogenic tumor. Orbital tumors in 56 cases were malignant(27.2%), the first three malignant tumors were orbital lymphoma, adenoid cystic carcinoma of the lacrimal gland and rhabdomyosarcoma. The most common orbital injury was orbital blowout fracture, followed by optic nerve injury and orbital soft tissue injury. Orbital non-infectious inflammation accounted for 89.8% and 10.2% with infectious inflammation.CONCLUSION: The spectrum of orbital diseases has changed, and the most common and dominant diseases are TAO, orbital tumor, orbital trauma and orbital inflammation, accounting for 96.8% of the total, which are the main work content in orbital profession. Medical resources of orbital diseases should be rationally allocated according to the changes of disease spectrum to meet the needs of social development.
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OBJECTIVE@#To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC).@*METHODS@#Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed.@*RESULTS@#There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic.@*CONCLUSION@#Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Biomarkers, Tumor , Carcinoma, Renal Cell/genetics , Fumarate Hydratase/genetics , In Situ Hybridization, Fluorescence , Kidney Neoplasms/genetics , PrognosisABSTRACT
BACKGROUND@#This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications.@*METHOD@#The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV's primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 μm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed.@*RESULTS@#The mean duration of surgery was 75 ± 9 min, and the mean blood loss was 20 ± 5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7° ± 4.3° to 48.0° ± 8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ± 0.5 to 1.3 ± 0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ± 3.3 to 18.5 ± 3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery.@*CONCLUSION@#The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Minimally Invasive Surgical Procedures , Methods , Printing, Three-Dimensional , Renal Nutcracker Syndrome , General Surgery , Retrospective Studies , Stents , Titanium , ChemistryABSTRACT
Background@#This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications.@*Method@#The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV’s primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 μm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed.@*Results@#The mean duration of surgery was 75 ± 9 min, and the mean blood loss was 20 ± 5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7° ± 4.3° to 48.0° ± 8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ± 0.5 to 1.3 ± 0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ± 3.3 to 18.5 ± 3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery.@*Conclusion@#The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.
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Objective: To study the effect of Huangqi Guizhi Wuwu Tang on angiogenesis of osteoarthritis with Yang deficiency and cold coagulation.Method: Totally 60 female SD rats were randomly divided into control group, model group, celecoxib group (20.82 mg·kg-1) and low, medium, high-dose Huangqi Guizhi Wuwu Tang groups (3.24, 6.48, 12.96 g·kg-1). All groups, except for control group, were involved in duplicating the osteoarthritis(OA) model through frozen and knee fixation, as well as 42-day cold environmental stimulation. After modeling, all drug-group rats were respectively administrated with corresponding drugs for 28 days, once a day. Meanwhile, control group and model group were given equivalent distilled water by gavage. 24 hours after the last gavage, vascular endothelial growth factor (VEGF),prostaglandin E2(PGE2) and transforming growth factor-β1(TGF-β1) in serum were detected with enzyme linked immunosorbent assay(ELISA) method, VEGF expressions in cartilage and synovial with immunohistochemical method, and interleukin-17(IL-17) and VEGF levels in synovial with Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).Result: Compared with normal group, the expression of VEGF in serum, cartilage and synovial were significantly increased (P2 and TGF-β1 expressions, IL-17 level were increased significantly (P2, TGF-β1 and IL-17 level were decreased significantly (PPPConclusion: Huangqi Guizhi Wuwu Tang has an effect in suppressing angiogenesis of knee and alleviate cartilage lesion by regulating VEGF and its upstream cytokines PGE2 and TGF-β1.
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Objective: To evaluate the preliminary efficacy and safety of the 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin (FOLF-OXIRI) and capecitabine, irinotecan, and oxaliplatin (CAPIRINOX) regimens as first-line therapy for unresectable advanced colorectal cancer. Methods: Between January 2013 and November 2018, 73 patients with metastatic colorectal cancer (mCRC) were analyzed. All patients received first-line chemotherapy. Of them, 45 patients were administered FOLFOXIRI, and the remaining 28 patients were ad-ministered CAPIRINOX. The clinical outcomes and safety profiles were evaluated according to the objective response rate (ORR), con-version resection rate, and adverse effects. Results: The ORR, median progression-free survival (mPFS), and R0 resection rate in the FOLFOXIRI group were not statistically different from those in the CAPIRINOX group (60% vs. 57.1%, 7.7 months vs. 9.6 months, 24.4% vs . 17.9% , respectively; P>0.05). No treatment-related deaths occurred. The major adverse events were leukopenia, neutropenia, fa-tigue, nausea, vomiting, diarrhea, alopecia, aspartate aminotransferase/alanine aminotransferase elevation, and neurotoxicity. The to-tal rate of grade 3/4 adverse events in the FOLFOXIRI group was 33.3% (15/45), while the total rate of grade 3/4 adverse events in the CAPIRINOX group was 46.4% (13/28). Toxicities between the two groups were not statistically significant (P=0.263). Conclusions: Both the FOLFOXIRI and CAPIRINOX regimens are effective as first-line treatment for metastatic colorectal cancer. The triple-agent chemo-therapy was associated with good efficacy and tolerable toxicity.
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Aim To investigate the potential protective effect of quercetin on chronic ethanol exposure induced autophagy dysfunction .Methods The male C57 BL/6 J mice were divided randomly into four groups: Nor-mal control group ( Con);Ethanol group ( Eth);Etha-nol plus Quercetin group ( Eth+Qu); Quercetin con-trol group ( Qu ) .The mice were pair-fed with either regular or ethanol-containing Lieber De Carli liquids diets for 15 weeks and the related parameters were as-sayed .Result Compared to Con group , chronic etha-nol feeding led to serious aminotransferases leakage , hepatic lipid accumulation , and liver oxidative dam-age.Additionally, long-term ethanol exposure caused lysosome damage , cathepsin B leakage to cytoplasm and decreased the expression of LAMP 2A which was the key protein for the autophagosome-lysosome fusion . As expect , quercetin supplementation evidently allevia-ted lysosome damage and decreased the abnormal LC 3-II and p62 accumulation , accelerated the autophago-some-lysosome fusion and increased the expression of LAMP2A.Conclusion Quercetin may alleviate the liver injury induced by chronic alcohol exposure by a-meliorating the lysosomal damage and up-regulating LAMP2 A expression .
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Objective To explore the effects of disease adaptation intervention in young and middle-aged patients undergoing early stage of peritoneal dialysis.Methods Using convenience sampling method,a total of 88 patients undergoing early stage of peritoneal dialysis were assigned into the experimental group and the control group from the inpatient ward of Nephrology Department of a tertiary hospital in Zhengzhou City.The experimental group received the comprehensive adaptation intervention and routine care,and the control group only received routine care.Before and after the intervention,the Psychosocial Adjustment to Illness Scale(PAIS-SR) and Short Form of 36 health survey questionnaire (SF-36) were used to assess the disease adaptability and quality of life of two groups,and the degree of edema and serum albumin index of two groups were recorded.Results Before and after the intervention,there were significant differences in the scores of psychosocial adaptation and each dimension,the scores of physical health and mental health in the experimental group,and the differences were statistically significant (P＜ 0.05);there were significant differences in the scores of psychosocial adaptation and each dimension in control group,and the differences were statistically significant(P＜0.05),but the differences of the scores of physical health and mental health were not statistically significant(P＞0.05).After the intervention,there were significant differences in the scores of psychosocial adaptation and each dimension,the scores of physical health and mental health between the two groups(P＜0.05);but the differences of serum albumin and edema index of two groups were not statistically significant(P＞0.05).Conclusion Comprehensive adaptation intervention can improve the ability of disease adaptation and the quality of life in young and middle-aged patients undergoing early stage of peritoneal dialysis.
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Objective To investigate the role of Sp1 in the regulation of transcription of vascular endothelial growth factor ( VEGF ) in hypoxia-induced HepG2 cells.Methods Quantitative real-time polymerase chain reaction and immunoblot assay were used to examine the effect of hypoxia on Sp1 protein and VEGF mRNA expression .Mithramycin A, the selective inhibitor of Sp1 and knock-out Sp1 gene with siRNA were used to examine the effect on VEGF mRNA expression induced by hypoxia in HepG2 cells.Results Hypoxia induced Sp1 protein and VEGF mRNA expression in HepG2 cells.Mithramycin A produced a concentration-dependent decrease of hypoxia-induced VEGF mRNA expression . After inhibition of Sp1 RNAi, VEGF mRNA expression was significantly repressed in HepG 2 cells.Conclusion Hypoxia can increase the expression of Sp1 protein and VEGF mRNA in HepG2 cells induced by hypoxia.The transcription of VEGF is regulated by Sp1 in hypoxia-induced HepG2 cells.
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Objective To investigate the role of Sp1 in the regulation of transcription of vascular endothelial growth factor ( VEGF ) in hypoxia-induced HepG2 cells.Methods Quantitative real-time polymerase chain reaction and immunoblot assay were used to examine the effect of hypoxia on Sp1 protein and VEGF mRNA expression .Mithramycin A, the selective inhibitor of Sp1 and knock-out Sp1 gene with siRNA were used to examine the effect on VEGF mRNA expression induced by hypoxia in HepG2 cells.Results Hypoxia induced Sp1 protein and VEGF mRNA expression in HepG2 cells.Mithramycin A produced a concentration-dependent decrease of hypoxia-induced VEGF mRNA expression . After inhibition of Sp1 RNAi, VEGF mRNA expression was significantly repressed in HepG 2 cells.Conclusion Hypoxia can increase the expression of Sp1 protein and VEGF mRNA in HepG2 cells induced by hypoxia.The transcription of VEGF is regulated by Sp1 in hypoxia-induced HepG2 cells.
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<p><b>BACKGROUND</b>Antiplatelet therapy (APT) was prevalently being used in the prevention of vascular disease, but the influence of prior APT on the prognosis of patients with intracerebral hemorrhage (ICH) remains controversial. This meta-analysis was to explore the effects of prior APT on the prognosis of patients with primary ICH.</p><p><b>METHODS</b>PubMed and Embase were searched to identify the eligible studies. The studies comparing the mortality of ICH patients with or without prior APT were included. The quality of these studies was evaluated by the Newcastle-Ottawa quality assessment scale. The adjusted or unadjusted odds ratio (OR) for mortality between ICH patients with and without prior APT were pooled with 95% confidence interval (95% CI) as the effect of this meta-analysis.</p><p><b>RESULTS</b>Twenty-two studies fulfilled the inclusion criteria and exhibited high qualities. The pooled OR was 1.37 (95% CI: 1.13-1.66, P = 0.001) for univariate analysis and 1.41 (95% CI: 1.05-1.90, P = 0.024) for multivariate analysis. The meta-regression indicated that for each 1-day increase in the time of assessment, the adjusted OR for the mortality of APT patients decreased by 0.0049 (95% CI: 0.0006-0.0091, P = 0.026) as compared to non-APT patients.</p><p><b>CONCLUSION</b>Prior APT was associated with high mortality in patients with ICH that might be attributed primarily to its strong effect on early time.</p>
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BACKGROUND/AIMS: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has been associated with an increased risk of hypertriglyceridemia (HT), there is no clear consensus within the scientific community. METHODS: A meta-analysis of 1,640 subjects from six individual studies was conducted to better elucidate the potential relationship between the LPL gene Pvu II polymorphism and HT within the Chinese population. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed effect models. RESULTS: Our analysis indicated a significant association between LPL gene Pvu II polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95% CI, 1.320 to 1.830; p = 1.158 × 10-7), recessive (OR, 0.540; 95% CI, 0.390 to 0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 × 10-8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 × 10-5), heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 × 10-6), and additive genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 × 10-7). CONCLUSIONS: Because LPL gene Pvu II restriction fragment length polymorphism polymorphism was associated with an elevated risk of HT, the P+ allele carriers of the LPL gene might be predisposed to HT.
Subject(s)
Humans , Alleles , Asian People , Consensus , Hypertriglyceridemia , Lipoprotein Lipase , Models, Genetic , Odds Ratio , Polymorphism, Restriction Fragment LengthABSTRACT
BACKGROUND/AIMS: The p22phox C242T gene polymorphism (rs4673) may be linked to an increased susceptibility for overt diabetic nephropathy (ODN), but the study results are still inconclusive. METHODS: To explore the relationship between p22phox C242T gene polymorphism and ODN, the current meta-analysis of 707 ODN patients and 745 controls from five individual studies was conducted. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were evaluated by either a random or fixed effect model. RESULTS: In our meta-analysis, a significant relationship between the p22phox C242T gene polymorphism and ODN was found under allelic (OR, 2.760; 95% CI, 1.400 to 5.450; p = 0.004), recessive (OR, 5.080; 95% CI, 1.020 to 25.430; p = 0.05), dominant (OR, 1.700; 95% CI, 1.167 to 2.477; p = 0.006), homozygous (OR, 3.900; 95% CI, 1.022 to 14.889; p = 0.046), heterozygous (OR, 1.523; 95% CI, 1.167 to 1.986; p = 0.002), and additive genetic models (OR, 2.019; 95% CI, 1.232 to 3.309; p = 0.005). CONCLUSIONS: A positive correlation between p22phox C242T gene polymorphism and ODN risk was found. The T allele carriers of p22phox C242T gene polymorphism might be predisposed to ODN.
Subject(s)
Humans , Alleles , Diabetic Nephropathies , Models, Genetic , Odds RatioABSTRACT
<p><b>BACKGROUND</b>Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI).</p><p><b>METHODS</b>Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups.</p><p><b>RESULTS</b>The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased.</p><p><b>CONCLUSIONS</b>The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.</p>
Subject(s)
Female , Humans , Infant, Newborn , Male , Brain , Pathology , Hypoxia-Ischemia, Brain , Diagnosis , Magnetic Resonance Imaging , MethodsABSTRACT
Objective: To clone altered phloem development (APL) genes from Taxus chinensis and reveal their potential regulatory role in tissues regeneration after bark girdling by investigating the expression profiles of these APLs. Methods: The full-length three APL genes were isolated using reverse transcription-polymerase chain reaction (RT-PCR) and were named as TcAPL1, TcAPL2, and TcAPL3, respectively. The expression profiles of these genes in different tissues and at different regeneration stages after bark girdling were analyzed by semi-quantitative RT-PCR and quantitative real-time PCR (qRT-PCR), respectively. Results: Phylogenetic tree analysis suggested that TcAPL1 and TcAPL2 could be clustered together with APL protein of Morus notabilis, which are closest in genetic relationship; TcAPL3 could be clustered with APL proteins of another big independent branch. The analysis of gene expression patterns in different tissues showed that the transcript abundances of TcAPL1 and TcAPL2 were mainly expressed in the roots, stems, leaves, and phloem with cambium; While TcAPL3 was higher in the leaves than that in the roots and xylem with cambium. Through analysis of the expression patterns in regeneration tissues after bark girdling, the mRNA expressions of TcAPL1 and TcAPL2 showed a up-down trend in the following periods and were found to decrease notably at 36 d after bark girdling, while the expression of TcAPL3 was repressed at all stages after bark girdling. Conclusion: In this study, three TcAPLs genes are cloned from T. chinensis, and their expressions are regulated in the regeneration processes after bark girdling. Our results demonstrate that APL might play a regulatory role in tissue regeneration after bark girdling in T. chinensis.
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<p><b>OBJECTIVE</b>To study the effect of aqueous extracts of Polygonum multiflorum (AEPM) on bile acid synthesis, metabolism and transfer-related molecules in rat liver and the hepatotoxicity-related mechanism of P. multiflorum.</p><p><b>METHOD</b>Sprague-Dawley rats were orally administered with 30, 60 g x kg(-1) APEM once everyday for consecutively 28 days. At the end of the experiment, mRNA and protein expressions of hepatic MRP3, MRP2, BSEP, FXR and CYP7A1 were detected by Real-time PCR and Western blot</p><p><b>RESULT</b>Compared with the normal group, the AEPM high dose group showed significant increases in mRNA expressions of hepatic MRP3 and BSEP of male rats (P < 0.05); AEPM high and low dose groups revealed a notable decrease in mRNA expressions of hepatic FXR (P < 0.05) and remarkable rises in mRNA expressions of hepatic MRP3, MRP2, BSEP, CYP7A1 among female rats (P < 0.05). According to the test results of western blot assay, AEPM high and low dose groups showed consistent changes in protein and mRNA expressions hepatic MRP3, MRP2, BSEP, FXR, CYP7A1.</p><p><b>CONCLUSION</b>The 28 oral administration with AEPM in rats showed a certain effect on expressions of bile acid synthesis, metabolism and transfer-related proteins, as well as cholestatic or choleretic effects in the mRNA expression.</p>
Subject(s)
Animals , Female , Male , Rats , Administration, Oral , Bile Acids and Salts , Metabolism , Cholestasis , Fallopia multiflora , Liver , Plant Extracts , Toxicity , Rats, Sprague-DawleyABSTRACT
AIM: To observe the clinical effect of phacoemulsification combined with intraocular lens implantation for high myopia ( axis oculi ≥ 30mm ) cataract, and to explore the causes and treatment methods of operation complications. METHODS: Selected 64 cases ( 86 eyes ) of cataract with high myopia patients (axis oculi ≥30mm), vision correction≤ 0. 1. Phacoemulsification combined with intraocular lens implantation was used. During 1a follow-up, the improvement of visual acuity and complications were observed. RESULTS: Postoperative best corrected visual acuity was ≥0. 4 in 35 eyes (41%), 0. 2-0. 3 in 23 eyes (27%), 0. 1-0. 15 in 25 eyes (29%), CONCLUSION: Phacoemulsification combined with intraocular lens implantation is a safe and ideal operation method for high myopia cataract, can obtain good effects, and the postoperative complications can be controlled. Because of the particularity of high myopia, operation should be gentle, technical parameters should be adjusted as appropriate, to achieve the best postoperative effects.
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<p><b>OBJECTIVE</b>To investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).</p><p><b>METHODS</b>Clinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.</p><p><b>RESULTS</b>Allele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.</p><p><b>CONCLUSION</b>MDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters , Genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Camptothecin , Therapeutic Uses , Colorectal Neoplasms , Drug Therapy , Genetics , Neoplasm Proteins , Genetics , Polymorphism, Single Nucleotide , Retrospective Studies , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of miR-34a in stage II-III colorectal cancer and to elucidate its association with recurrence after radical resection.</p><p><b>METHODS</b>miR-34a expression level was detected in colorectal cancer patients with recurrence (40 cases) and without recurrence (40 cases) within 3 years after radical operation by real-time RT-PCR.</p><p><b>RESULTS</b>No association was observed between miR-34a and gender, age, location, local invasion, lymph node metastasis, cancer embolus, or tissue differentiation (all P>0.05). The expression level of miR-34a was lower in patients with recurrence compared to those without recurrence after radical surgery (P=0.039). Univariate analysis indicated that the median disease-free surviva l(DFS) of patients with low expression of miR-34a was worse as compared to those with high miR-34a expression (13.4 vs. 18.4 months, P=0.010), especially for stage III (P=0.003). In the recurrence group, the median DFS of patients with low miR-34a expression (n=14) was 13.4 months, which was shorter than that of patients with high miR-34a expression (n=26, 18.4 months, P=0.037). Multivariate analysis showed that miR-34a expression was an independent factor for colorectal cancer recurrence (RR=0.397, 95%CI:0.205-0.768, P=0.006).</p><p><b>CONCLUSION</b>The down-regulated expression of miR-34a in colorectal cancer patients is associated with recurrence after radical operation. miR-34a may be a marker to predict tumor recurrence and metastasis of colorectal carcinoma.</p>