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Lower serum bilirubin concentration in patients with migraine. - International journal of clinical and experimental medicine
Bilirubin has been seen as a toxic waste product since it is product of heme metabolism. It's the latest in a series of studies showed that the concentration of serum bilirubin is associated with various diseases such as multiple sclerosis, hypertension and cardiovascular diseases (CVD). However, no study to investigate the association between serum bilirubin and migraine, thus, our aim is to investigate the association between serum bilirubin and migraine.Serum samples were collected from 120 patients with migraine and 128 healthy individuals, serum total bilirubin (Tbil), serum direct bilirubin (Dbil) and serum indirect bilirubin (Ibil) concentration were measured to this study.Tbil, Dbil and Ibil concentration were significantly lower in patients with migraine than healthy controls. Tbil, Dbil and Ibil concentration also were lower in patients with migraine compared with healthy controls when serum bilirubin concentration further was grouped by gender.We found evidence that lower serum bilirubin in patients with migraine, serum bilirubin may be useful markers to estimate neurogenic inflammation in patients with migraine.
Down-regulation of multiple CDK inhibitor ICK/KRP genes promotes cell proliferation, callus induction and plant regeneration in Arabidopsis. - Frontiers in plant science
The ICK/KRP cyclin-dependent kinase (CDK) inhibitors are important plant cell cycle regulators sharing only limited similarity with the metazoan CIP/KIP family of CDK inhibitors. Information is still limited regarding the specific functions of different ICK/KRP genes in planta. We have shown previously that down-regulation of multiple CDK inhibitor ICK/KRP genes up-regulates the E2F pathway and increases cell proliferation, and organ and seed sizes in Arabidopsis. In this study, we observed that the quintuple ick1/2/5/6/7 mutant had more cells in the cortical layer of the root apical meristem (RAM) than the wild type (Wt) while its RAM length was similar to that of the Wt, suggesting a faster cell cycle rate in the quintuple mutant. We further investigated the effects of down-regulating ICK genes on tissue culture responses. The cotyledon explants of ick1/2/5/6/7 could form callus efficiently in the absence of cytokinin and also required a lower concentration of 2,4-D for callus induction compared to the Wt plants, suggesting increased competence for callus induction in the mutant. In addition, the quintuple ick mutant showed enhanced abilities to regenerate shoots and roots, suggesting that increased competence to enter the cell cycle in the quintuple mutant might make it possible for more cells to become proliferative and be utilized to form shoots or roots. These findings indicate that CDK activity is a major factor underlying callus induction and increased cell proliferation can enhance in vitro organogenesis.
Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis. - Oncotarget
Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed (p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.
Local production of the chemokines CCL5 and CXCL10 attracts CD8+ T lymphocytes into esophageal squamous cell carcinoma. - Oncotarget
Esophageal squamous cell carcinoma (ESCC) is a very common malignant tumor with poor prognosis in China. Chemokines secreted by tumors are pivotal for the accumulation of CD8+ T lymphocytes within malignant lesions in several types of cancers, but the exact mechanism underlying CD8+ T lymphocyte homing is still unknown in ESCC. In this study, we revealed that, compared with marginal tissues, the expression of both chemokine (C-C motif) ligand 5 (CCL5) and (C-X-C motif) ligand 10 (CXCL10) was upregulated in ESCC tissues. CCL5 expression was positively associated with the overall survival of patients. Meanwhile, RT-PCR data showed that the expression of CCL5 and CXCL10 was positively correlated with the local expressions of the CD8+ T lymphocyte markers (CD8 and Granzyme B) in tumor tissues. Correspondingly, CD8+ T lymphocytes were more frequently CCR5- and CXCR3-positive in tumor than in peripheral blood. Transwell analysis showed both CCL5 and CXCL10 were important for the chemotactic movement of CD8+ T lymphocytes. Our data indicate that CCL5 and CXCL10 serve as the key chemokines to recruit CD8+ T lymphocytes into ESCC tissue and may play a role in patient survival.
Spironolactone Add-on for Preventing or Slowing the Progression of Diabetic Nephropathy: A Meta-analysis. - Clinical therapeutics
The aim of this meta-analysis was to evaluate the benefits and potential adverse effects of adding spironolactone to standard antidiabetic/renoprotective/antihypertensive (AD/RP/AHT) treatment in patients with diabetic nephropathy (DN).PubMed/MEDLINE and Web of Knowledge were searched for relevant randomized, controlled studies (RCTs) or quasi-RCTs of the effects of adding spironolactone to standard AD/RP/AHT treatment in patients with DN. Results were summarized with a random-effects model or a fixed-effects model.According to the outcomes measured (benefits and risks of adding spironolactone to standard AD/RP/AHT treatment), compared with controls, the addition of spironolactone significantly decreased end-of-treatment (EOT) 24-hour urinary albumin/protein excretion and significantly increased percentage reduction from baseline in urinary albumin/creatinine ratio (UACR), although it did not significantly affect EOT UACR. The addition of spironolactone further led to a significantly greater reduction from baseline in glomerular filtration rate (GFR)/estimated (e) GFR, although it did not significantly affect EOT GFR/eGFR. Further, the addition of spironolactone significantly reduced EOT in-office, 24-hour, and daytime systolic and diastolic blood pressure (SBP and DBP, respectively) and led to significantly greater reductions from baseline in in-office SBP and DBP, although it did not significantly affect nighttime SBP or DBP. Finally, the addition of spironolactone significantly increased mean serum/plasma potassium levels and the risk for hyperkalemia.Spironolactone could be added to preexisting AD/RP/AHT therapy in patients with DN to prevent or slow DN progression by reducing proteinuria. The addition of spironolactone would likely provide even more beneficial effect in patients with DN and hypertension due to the BP reduction associated with spironolactone use. However, the beneficial effects of spironolactone add-on should be weighed against its potential risks, especially hyperkalemia. The long-term effects of spironolactone add-on on renal outcomes and mortality need to be studied.Copyright Â© 2015. Published by Elsevier Inc.
Association between Serum Fructosamine and Kidney Function in Nondiabetic Individuals without Chronic Kidney Disease. - Medical science monitor : international medical journal of experimental and clinical research
Serum fructosamine (SF) has been considered to be an indicator that estimates glycemic control in patients with diabetes mellitus (DM). There is increasing evidence that SF concentration and oxidative stress are significantly elevated in patients with chronic kidney disease (CKD). However, the data about SF and its association with kidney function are lacking in nondiabetic individuals without CKD. We included 1891 nondiabetic individuals who had not been diagnosed with CKD to determine the association between SF and kidney function.We conducted a retrospective analysis on the basis of the biochemistry database in nondiabetic individuals without CKD.When eligible participants were stratified in accordance with SF quartiles, from the bottom to the top quartile of SF, a significant decrease of estimated glomerular filtration rate (GFR) was observed in baseline data. SF concentration was negatively associated with estimated GFR (r=-0.066, P=0.004) in the Pearson correlation analysis. Estimated GFR was associated with SF levels independently of glucose (GLU), total cholesterol (TC), triglyceride (TG), and total protein (TP) in multivariable logistic regression analysis (OR=0.984; CI 95% 0.977-0.991; P<0.001).We suggest that mild elevation of SF concentration is associated with estimated GFR in nondiabetic individuals without CKD. These findings indicate that SF may underlie CKD in nondiabetic individuals.
Ginsenoside rh2 inhibits cancer stem-like cells in skin squamous cell carcinoma. - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined.Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and Î²-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and Î²-catenin were used to inhibit autophagy and Î²-catenin signaling pathway, respectively, as loss-of-function experiments.We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced Î²-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on Î²-catenin and cell viability, while increasing Î²-catenin abolished the effects of GRh2 on autophagy and cell viability.Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and Î²-catenin signaling.Â© 2015 S. Karger AG, Basel.
[Application of precursor ion scanning method in rapid screening of illegally added phosphodiesterase-5 inhibitors and their unknown derivatives in Chinese traditional patent medicines and health foods]. - Se pu = Chinese journal of chromatography / Zhongguo hua xue hui
The compounds with similar structure often have similar pharmacological activities. So it is a trend for illegal addition that new derivatives of effective drugs are synthesized to avoid the statutory test. This bring challenges to crack down on illegal addition behavior, however, modified derivatives usually have similar product ions, which allow for precursor ion scanning. In this work, precursor ion scanning mode of a triple quadrupole mass spectrometer was first applied to screen illegally added drugs in complex matrix such as Chinese traditional patent medicines and healthy foods. Phosphodiesterase-5 inhibitors were used as experimental examples. Through the analysis of the structure and mass spectrum characteristics of the compounds, phosphodiesterase-5 inhibitors were classified, and their common product ions were screened by full scan of product ions of typical compounds. Then high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with precursor ion scanning mode was established based on the optimization of MS parameters. The effect of mass parameters and the choice of fragment ions were also studied. The method was applied to determine actual samples and further refined. The results demonstrated that this method can meet the need of rapid screening of unknown derivatives of phosphodiesterase-5 inhibitors in complex matrix, and prevent unknown derivatives undetected. This method shows advantages in sensitivity, specificity and efficiency, and is worth to be further investigated.
Intrapulmonary lipoma: a case report and literature review. - World journal of pediatrics : WJP
Intrapulmonary lipoma is extemely rare in children. So far, all reported pulmonary lipomas were from adult patients.We present herein a case of intrapulmonary lipoma in a child and a review of the related literature.A 13-month-old boy was hospitalized because of cough and fever. Chest CT showed patchy infiltration and round-shape, hypodense homogeneous lesions located in the lung. After 19 days of antibiotic treatment, his clinic symptoms disappeared, but the round lesions remained without any change. One month and one year later, he was examined by chest MRI with technique of fat suppression. The child was diagnosed as having an intrapulmonary lipoma without biopsy.Intrapulmonary lipoma is rare in children. Chest CT and MRI are very important for the correct diagnosis of intrapulmonary lipoma.
Transcriptome sequencing of Codonopsis pilosula and identification of candidate genes involved in polysaccharide biosynthesis. - PloS one
Codonopsis pilosula (Franch.) Nannf. is one of the most widely used medicinal plants. Although chemical and pharmacological studies have shown that codonopsis polysaccharides (CPPs) are bioactive compounds and that their composition is variable, their biosynthetic pathways remain largely unknown. Next-generation sequencing is an efficient and high-throughput technique that allows the identification of candidate genes involved in secondary metabolism.To identify the components involved in CPP biosynthesis, a transcriptome library, prepared using root and other tissues, was assembled with the help of Illumina sequencing. A total of 9.2 Gb of clean nucleotides was obtained comprising 91,175,044 clean reads, 102,125 contigs, and 45,511 unigenes. After aligning the sequences to the public protein databases, 76.1% of the unigenes were annotated. Among these annotated unigenes, 26,189 were assigned to Gene Ontology categories, 11,415 to Clusters of Orthologous Groups, and 18,848 to Kyoto Encyclopedia of Genes and Genomes pathways. Analysis of abundance of transcripts in the library showed that genes, including those encoding metallothionein, aquaporin, and cysteine protease that are related to stress responses, were in the top list. Among genes involved in the biosynthesis of CPP, those responsible for the synthesis of UDP-L-arabinose and UDP-xylose were highly expressed.To our knowledge, this is the first study to provide a public transcriptome dataset prepared from C. pilosula and an outline of the biosynthetic pathway of polysaccharides in a medicinal plant. Identified candidate genes involved in CPP biosynthesis provide understanding of the biosynthesis and regulation of CPP at the molecular level.
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43713 Boscell Rd Fremont, CA 94538