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Biomedical subjects

Han Chen

Publications and source records attributed to Han Chen.

At least 19 recordsLinked to original sources

Detoxification-driven recovery of nitrogen removal under high linear alkylbenzene sulfonate stress by immobilized Pseudomonas sp. LM2.

Linear alkylbenzene sulfonate (LAS) is a widely used anionic surfactant that can inhibit microbial activity and destabilize biological wastewater treatment systems under high loading conditions. In this study, a sequencing batch reactor (SBR) was exposed to increasing LAS concentrations (0-100 mg/L) to define the collapse trajectory of activated sludge and evaluate recovery following bioaugmentation with immobilized Pseudomonas sp. LM2. The system remained stable at 20 mg/L LAS, deteriorated after prolonged exposure to 50 mg/L, and developed severe sludge disintegration with near-complete nitrification failure at 100 mg/L. In the LM reactor, LAS removal increased from 25.4% to 53.1% after bioaugmentation, together with improved nitrogen-removal performance. Blank carriers did not restore reactor performance. Genome annotation showed that LM2 encoded genes associated with LAS degradation and denitrification but lacked nitrification genes. Thus, the observed nitrification recovery was likely indirect and associated with lower LAS stress and recovery of indigenous nitrifiers. Quantitative PCR and amplicon analyses showed enrichment of Nitrospira and Thauera and a shift toward more deterministic community assembly after bioaugmentation. The carrier-only control showed taxonomic recovery but persistent functional inhibition under high residual LAS exposure. Overall, the results indicate that immobilized bioaugmentation can support partial recovery of nitrogen removal under severe LAS stress.

Bioaugmentation↗

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using &#x3c7;2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6&#x2009;months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p&#x2009;<&#x2009;0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p&#x2009;>&#x2009;0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans↗

Genetic architecture and analysis practices of circulating metabolites in the NHLBI Trans-Omics for Precision Medicine Program.

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. From our comparison of multiple methods, we provided a set of reasonable strategies for outlier and imputation handling to process metabolite data and show that inverse normalization by study and half-minimum imputation provide mostly similar results for pooled or meta-analysis. Following the practical analysis framework, we further performed a genome-wide association analysis on 1,135 selected metabolites using whole-genome sequencing data from 16,359 individuals passing the quality-control filters and discovered 1,775 independent loci associated with 667 metabolites. Among 160 unreported locus-metabolite pairs, we identified associations with loci locating within previously implicated metabolite-associated genes, as well as associations with loci locating in genes such as GAB3 and VSIG4 (located on the X chromosome) that may play a role in metabolic regulation. In the sex-stratified analysis, we revealed 85 independent locus-metabolite pairs with evidence of sexual dimorphism, which were located in well-known metabolic genes such as FADS2, D2HGDH, SUGP1, and UGT2B17, strongly supporting the importance of exploring sex difference in the human metabolome. Taken together, our study depicted the genetic contribution to circulating metabolite levels, providing additional insight into the understanding of human health.

Humans↗

Polygenic scores for obstructive sleep apnoea reveal pathways contributing to cardiovascular disease.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common chronic condition, with obesity its strongest risk factor. Polygenic scores (PGSs) summarise the genetic liability to phenotype and can provide insights into relationships between phenotypes. Recently, large datasets that include genetic data and OSA status became available, providing an opportunity to utilise PGS approaches to study the genetic relationship between OSA and other phenotypes, while differentiating OSA-specific from obesity-specific genetic factors. METHODS: Using race/ethnic diverse samples from over 1.2 million individuals from the Million Veteran Program, FinnGen, TOPMed, All of Us (AoU), Geisinger's MyCode, MGB Biobank, and the Human Phenotype Project, we developed and assessed PGSs for OSA, both without (BMIunadjOSA-PGS) and with adjustment for the genetic contributions of BMI (BMIadjOSA-PGS). FINDINGS: Adjusted odds ratios (ORs) for OSA per 1 standard deviation of the PGSs ranged from 1.38 to 2.75. The associations of BMIadjOSA- and BMIunadjOSA-PGSs with CVD outcomes in AoU shared both common and distinct patterns. Only BMIunadjOSA-PGS was associated with type 2 diabetes, heart failure, and coronary artery disease, while both BMIadjOSA- and BMIunadjOSA-PGSs were associated with hypertension and stroke. Sex stratified analyses revealed that BMIadjOSA-PGS association with hypertension was driven by females (OR = 1.1, p-value = 0.002, OR = 1.01 p-value = 0.2 in males). OSA PGSs were also associated with body fat measures with some sex-specific associations. INTERPRETATION: Distinct components of OSA genetic risk are related and independent of obesity. Sex-specific associations with body fat distribution measures may explain differing OSA risks and associations with cardiometabolic morbidities between sexes. FUNDING: R01AG080598.

Humans↗

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup. We define a metric called "expected PRS" (ePRS), the expected value of a PRS based on one's global or local admixture patterns. We further define the "residual PRS" (rPRS), measuring the deviation of the PRS from the ePRS. Simulation studies confirm that it suffices to adjust for ePRS to obtain nearly unbiased estimates of the PRS-outcome association without further adjusting for PCs. Using the TOPMed dataset, the estimated effect size of the rPRS adjusting for the ePRS is similar to the estimated effect of the PRS adjusting for genetic PCs. Similarly, we applied the ePRS framework to six cardiovascular-related traits in the All of Us dataset, and the results are consistent with those from the TOPMed analysis. The ePRS framework can protect from population stratification in association analysis and provide an equitable strategy to quantify genetic risk across diverse populations.

Journal Article↗

Biodesulfurization of dibenzothiophene by growing cells of Gordonia sp. in batch cultures.

A new isolate, identified as Gordonia sp. ZD-7 by 16S rDNA sequence analysis, grew in n-hexadecane containing dibenzothiophene (DBT) which was degraded from 2.8 mM to 0.2 mM within 48 h. Biodesulfurization could be repeatedly performed for more than 190 h, with average desulfurization rates of 5 mmol DBT kg cells (dry wt)(-1) h(-1).

Biodegradation, Environmental↗

Positive regulatory domain I-binding factor 1 mediates repression of the MHC class II transactivator (CIITA) type IV promoter.

MHC class II transactivator (CIITA), a co-activator that controls MHC class II (MHC II) transcription, functions as the master regulator of MHC II expression. Persistent activity of the CIITA type III promoter (pIII), one of the four potential promoters of this gene, is responsible for constitutive expression of MHC II by B lymphocytes. In addition, IFN-gamma induces expression of CIITA in these cells through the type IV promoter (pIV). Positive regulatory domain 1-binding factor 1 (PRDI-BF1), called B lymphocyte-induced maturation protein 1 (Blimp-1) in mice, represses the expression of CIITA pIII in plasma and multiple myeloma cells. To investigate regulation of CIITA pIV expression by PRDI-BF1 in the B lymphocyte lineage, protein/DNA-binding studies, and functional promoter analyses were performed. PRDI-BF1 bound to the IFN regulatory factor-element (IRF-E) site in CIITA pIV. Ectopic expression of either PRDI-BF1 or Blimp-1 repressed this promoter in B lymphocytes. In vitro binding and functional analyses of CIITA pIV demonstrated that the IRF-E is the target of this repression. In vivo genomic footprint analysis demonstrated protein binding at the IRF-E site of CIITA pIV in U266 myeloma cells, which express PRDI-BF1. PRDI-BF1beta, a truncated form of PRDI-BF1 that is co-expressed in myeloma cells, also bound to the IRF-E site and repressed CIITA pIV. These findings demonstrate for the first time that, in addition to silencing expression of CIITA pIII in B lymphocytes, PRDI-BF1 is capable of binding and suppressing CIITA pIV.

B-Lymphocytes↗

Studying the signaling role of 2-oxoglutaric acid using analogs that mimic the ketone and ketal forms of 2-oxoglutaric acid.

2-Oxoglutaric acid (2-OG), a Krebs cycle intermediate, is a signaling molecule in many organisms. To determine which form of 2-OG, the ketone or the ketal form, is responsible for its signaling function, we have synthesized and characterized various 2-OG analogs. Only 2-methylenepentanedioic acid (2-MPA), which resembles closely the ketone form of 2-OG, is able to elicit cell responses in the cyanobacterium Anabaena by inducing nitrogen-fixing cells called heterocysts. None of the analogs mimicking the ketal form of 2-OG are able to induce heterocysts because none of them are able to interact with NtcA, a 2-OG sensor. NtcA interacts with 2-MPA and 2-OG in a similar manner, and it is necessary for heterocyst differentiation induced by 2-MPA. Therefore, it is primarily the ketone form that is responsible for the signaling role of 2-OG in Anabaena.

Anabaena↗

[Analysis of the nutrients contents and the blood glucose response of the mixed grains in Chinese people].

OBJECTIVE: To evaluate the nutrients contents and the glycemic index (GI) of the mixed grains and analyze the relationship between the nutrients contents and biological effect. METHODS: The nutrients contents of mixed grains and control food were determined according to the methods of Chinese national standards. Choose 10 volunteers to ingest 50 g glucose and ingest the steamed bread of mixed grains which imply 50 g carbohydrate the second day. Limosis blood glucose and blood glucose levels during the subsequent 3 hours were determined. Calculating the GI according to the Wolver's method. RESULTS: The results showed that 100 g of the mixed grains contained dietary fiber (crude fiber) 13.7 g, vitamin B1 0.40 mg, protein 13.5g, ash2.0g, vitamin B2 0.16 mg, calcium 54 mg, iron 7.1 mg and zinc3.00 mg respectively. The absolute increase of blood glucose and the areas increased under the glycemic curves of mixed grains were less than which of glucose (P < 0.05). The GI of the mixed grains bread was 52.6. CONCLUSION: It was concluded that the high contents of protein, minerals, dietary fiber, VB1, VB2 and the low GI of mixed grains might play an important role in nutritional intervention

Adult↗

[Studies on effect enhancement of the Schistosoma japonicum DNA vaccine pVIV02-IL12-Sj23 by vegetal polysaccharides].

OBJECTIVE: To enhance the immunogenicity of the recombinant pVIVO2-IL12-Sj23 vaccine of Schistosoma japonicum by using mixed vegetal polysaccharides as adjuvant. METHODS: The plasmid pVIVO2-IL12-Sj23 was constructed. 3 groups of BALB/C mice were injected intramuscularly with normal saline (Group A), pVIVO2-IL12-Sj23 plasmid DNA (B), and pVIVO2-IL12-Sj23 plus mixed vegetal polysaccharides (C) respectively, and challenged with S. japonicum cercariae on the 4th week after immunization. Mice were killed to calculate the worm reduction rate and egg reduction rate in liver tissue on the 6th week after infection. Before and 4 weeks after immunization blood samples were collected. RESULTS: The worm reduction rate and egg reduction rate were 64.3% and 79.9%, respectively in group C, 45.5% and 58.4%, respectively in group B, showing a remarkable difference hetween them (P < 0.05). ELISA analysis showed a significantly higher level of IgG specific for Sj23 4 weeks after vaccination in groups B and C (P < 0.05). However, there was no significant difference in IgG level between groups C and B (P > 0.05). CONCLUSION: When mixed vegetal polysaccharides are used as adjuvant, the effect of the vaccine pVIVO2-IL12-Sj23 can he considerably enhanced.

Adjuvants, Immunologic↗

Nonmetabolizable analogue of 2-oxoglutarate elicits heterocyst differentiation under repressive conditions in Anabaena sp. PCC 7120.

In response to combined nitrogen starvation in the growth medium, the filamentous cyanobacterium Anabaena sp. PCC 7120 is able to develop a particular cell type, called a heterocyst, specialized in molecular nitrogen fixation. Heterocysts are regularly intercalated among vegetative cells and represent 5-10% of all cells along each filament. In unicellular cyanobacteria, the key Krebs cycle intermediate, 2-oxoglutarate (2-OG), has been suggested as a nitrogen status signal, but in vivo evidence is still lacking. In this study we show that nitrogen starvation causes 2-OG to accumulate transiently within cells of Anabaena PCC 7120, reaching a maximal intracellular concentration of approximately 0.1 mM 1 h after combined nitrogen starvation. A nonmetabolizable fluorinated 2-OG derivative, 2,2-difluoropentanedioic acid (DFPA), was synthesized and used to demonstrate the signaling function of 2-OG in vivo. DFPA is shown to be a structural analogue of 2-OG and the process of its uptake and accumulation in vivo can be followed by (19)F magic angle spinning NMR because of the presence of the fluorine atom and its chemical stability. DFPA at a threshold concentration of 0.3 mM triggers heterocyst differentiation under repressing conditions. The multidisciplinary approaches using synthetic fluorinated analogues, magic angle spinning NMR for their analysis in vivo, and techniques of molecular biology provide a powerful means to identify the nature of the signals that remain unknown or poorly defined in many signaling pathways.

Anabaena↗

Expression of the MHC class II transactivator (CIITA) type IV promoter in B lymphocytes and regulation by IFN-gamma.

The MHC class II transactivator (CIITA), the master regulator of MHC class II (MHC II) expression, is a co-activator that controls MHC II transcription. Human B lymphocytes express MHC II constitutively due to persistent activity of CIITA promoter III (pIII), one of the four potential promoters (pI-pIV) of this gene. Although increases in MHC II expression in B cells in response to cytokines have been observed and induction of MHC II and CIITA by IFN-gamma has been studied in a number of different cell types, the specific effects of IFN-gamma on CIITA expression in B cells have not been studied. To investigate the regulation of CIITA expression by IFN-gamma in B cells, RT-PCR, in vivo and in vitro protein/DNA binding studies, and functional promoter analyses were performed. Both MHC II and CIITA type IV-specific RNAs increased in human B lymphocytes in response to IFN-gamma treatment. CIITA promoter analysis confirmed that pIV is IFN-gamma inducible in B cells and that the GAS and IRF-E sites are necessary for full induction. DNA binding of IRF-1 and IRF-2, members of the IFN regulatory factor family, was up-regulated in B cells in response to IFN-gamma and increased the activity of CIITA pIV. In vivo genomic footprint analysis demonstrated proteins binding at the GAS, IRF-E and E box sites of CIITA pIV. Although CIITA pIII is considered to be the hematopoietic-specific promoter of CIITA, these findings demonstrate that pIV is active in B lymphocytes and potentially contributes to the expression of CIITA and MHC II in these cells.

B-Lymphocytes↗

[Clinical evaluation of nickel-titanium rotary instruments Hero 642 in root canal preparation].

PURPOSE: This research is aimed to assess the clinical value of the Nickel-titanium (NiTi) rotary instruments Hero 642 in root canal preparation. METHODS: 60 molars were instrumented by Hero 642 rotary instruments using crown-down technique in the experimental group, and by K files using step-back technique in the control group. All teeth were obturated with lateral condensation method. The efficiency of preparation and obturation was analyzed by radiographs before and after treatment. The canal curvature and operation time were compared by means of Student's t test, and the incidence of complications and post-treatment pain were compared by means of Chi square test between two groups. RESULTS: No transportation, apical blockage, ledge or perforation was found in the experimental group. The Hero 642 instruments could keep the original curvature and flow of the root canals. There was more canal complications in the control group than in the experimental group (P<0.005). The operative time was shorter and post treatment pain seldom occurred in the experimental group. CONCLUSION: The NiTi rotary instruments Hero 642 can be used for preparation of root canals effectively and safely, and is worth wide application.

Humans↗

[Clinical evaluation of two types of NiTi rotary instruments in preparation of root canals].

OBJECTIVE: To evaluate clinical effects of two types of nickel-titanium rotary instruments in preparation of molars' root canals. METHODS: 100 molars with pupal and periapical involvement were instrumented by Protaper and Hero642 files with crown-down technique. All teeth were obturated with lateral condensation method. Straightening of canal curvature was determined. The efficiency of preparation and obturation was analyzed with radiograph before, during and after operation. RESULTS: The operating time of each NiTi group was short. The two NiTi rotary instruments could achieve continuously tapered root canal shape. The curvature of the canal reduced by -4.02 degrees +/- 2.80 degrees with Protaper and 1.72 degrees with Hero642 (P < 0.001). Five pieces of Protaper with broken, whereas no Hero642 was broken (P < 0.05). CONCLUSIONS: Protaper, Hero642 files showed good shaping ability and improved predictability in root canal obturation. Protaper can lessen canal curvature more significantly. Hero642 files are easy to operate and not easy to separate.

Adult↗

[MGB probes detect Streptococcus mutans and Streptococcus sobrinus in real time].

OBJECTIVE: To detect and distinguish Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus) quickly in epidemiology and investigate the distribution of S. mutans in the oral of children with rampant caries. METHODS: Designed minor groove binder (MGB) probes according to the gtf gene of S. mutans and S. sobrinus. Detected 9 reference strains of Streptococcus mutans group by MGB probes in real time and after cultivation. Evaluated the results of these two methods. 92 dental plaques from pre-school children with rampant caries were detected in real time with MGB probes. RESULTS: The primers could amplify the target sequences specificity and distinguished S. mutans and S. sobrinus from each other using MGB probes. Though the fluorescence occurred earlier in S. mutans than in S. sobrinus, they had the same results in nature. In 92 children with rampant caries, the detective ratio of S. mutans was 96.7% and that of S. sobrinus was 32.6%. All the samples which could detect S. sobrinus were positive for S. mutans. CONCLUSION: The primers and probe designed from gtf genes of S. mutans and S. sobrinus can amplify the target sequence and distinguish them from each other in real time.

Child↗

[Anti-viral therapy using lamivudine and thymosin is helpful to prevent recurrence in hepatocellular carcinoma with coexisting active hepatitis B].

OBJECTIVE: To observe the effect of postoperative anti-viral therapy using lamivudine and thymosin alpha1 on recurrence of hepatocellular carcinoma (HCC) coexisting with active hepatitis B. METHODS: From Jan. 2000 to Dec. 2002, 33 HCC patients with coexisting with active hepatitis B were randomized into two groups: Group I (n = 17) received hepatectomy only, and Group II (n = 16) received hepatectomy and postoperative therapy using lamivudine plus thymosin alpha1. The suppression of HBV-DNA, HBeAg seroconversion rate, tumor recurrence rate and median survival in the two groups were observed and compared. RESULTS: In Group II and Group I, the 1-year HBV-DNA suppression rate was 100.0% vs 6.0% (P < 0.01), HBeAg seroconversion rate was 62.5% vs 5.9% (P < 0.05), tumor recurrence rate was 81.3% vs 95.5% (P > 0.05), the recurrence time was 7.0 vs 5.0 months (P < 0.01) and median survival 10.0 vs 7.0 months (P < 0.01). CONCLUSION: Anti-viral therapy using lamivudine and thymosin alpha1 postoperatively may suppress the HBV reaction, delay the recurrence and prolong the survival for patients with HCC with coexisting active hepatitis B.

Adult↗

[Hepatocellular carcinoma with tumor thrombi in the portal vein. A comparison of therapeutic effects by different treatments].

OBJECTIVE: To investigate the effects of different treatments for hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein (PVTT). METHODS: From Jan. 2000 to Jan. 2003, a total of 84 HCC patients with PVTT were divided into five groups based on methed of treatment: Group A (n = 9), HCC resection + PVTT removal + postoperative TACE + thymosin alpha(1); Group B (n = 20), HCC resection + PVTT removal + postoperative TACE; Group C (n = 7), HCC resection + PVTT removal; Group D (n = 38), TACE only; Group E (n = 10), conservative treatment only. RESULTS: The rate of PVTT shrinkage or disappearance of groups A, B, C, D and E was 66.7%, 70.0%, 57.1%, 7.9% and 0, respectively with respective median survival time of 10.0, 7.0, 8.0, 5.0 and 2.0 months. The one year survival rate was 44.4%, 15.0%, 14.3%, 10.5% and 0. CONCLUSION: Resection of HCC and removal of tumor thrombus in the portal vein may have the tumor thrombus cleared in most of the patients and postoperative TACE and thymisin alpha(1) treatment may improve their survival.

Adult↗

[Clinical evaluation of three nickel-titanium rotary instruments in preparation of curved root canals].

OBJECTIVE: This research aimed to study and assess clinical application of the using of three Nickel-titanium (NiTi) rotary instruments, namely ProFile, ProTaper and Hero 642, in preparation of curved root canals. METHODS: 80 teeth with curved root canals were instrumented by ProFile, ProTaper or Hero 642 rotary instruments using crown-down technique in test groups and by stainless steel K files in control group. All teeth were obturated with lateral condensation method. The efficiency of preparation and obturation was analyzed with radiographs before, during and after operation. RESULTS: Three NiTi rotary instruments could keep the curvature and flow of curved canals very well, and the continuously tapered root canal shape was achieved. There were no transportation, apical blockage, and ledge in all test groups. The operative time was shorter for ProTaper than that of ProFile and Hero 642. Endodontic flare-up seldom occurred in test groups. Two rotary instruments fractured in canals. CONCLUSION: With the NiTi rotary instruments, ProFile, ProTaper and Hero 642, curved root canals can be prepared effectively and quickly. Meanwhile, the problem of instrument separation should be prevented.

Dental Alloys↗