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Biomedical subjects

Wei Zhou

Publications and source records attributed to Wei Zhou.

At least 127 records · Page 7Linked to original sources

Single-walled carbon nanotube-templated crystallization of H2SO4: direct evidence for protonation.

Liquid anhydrous sulfuric acid forms molecular "shells" wrapped around single-walled carbon nanotubes (SWNTs). Temperature-dependent X-ray scattering from aligned acid-swollen fibers shows that crystallization of the bulklike acid surrounding the structured shells is templated by the aligned SWNTs, while the structured shells remain partly ordered, at least for temperatures from 100 to 500 K. The (2 0 0) or ( 0 2) planes of the templated H2SO4 crystallites are parallel to the nanotube axes. This provides solid evidence for the direct protonation of SWNT since the molecules are terminated by hydrogen bonds.

Journal Article↗

Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer.

PURPOSE: To determine whether the nonselective and relatively inexpensive nonsteroidal anti-inflammatory drug ibuprofen would be effective in inhibiting colorectal cancer and might improve mortality in a mouse model. EXPERIMENTAL DESIGN: The effects of ibuprofen on tumor growth inhibition and animal survival have been examined in both mouse and human colorectal cancer tumor models. Angiogenesis was measured by in vitro endothelial cell tube formation and immunohistochemistry. RESULTS: Ibuprofen significantly inhibited cell proliferation in mouse (MC-26) and human (HT-29) colorectal cancer cell lines. In vitro angiogenesis assays also indicated that ibuprofen decreased both cell proliferation and tube formation. The administration of chow containing 1,360 ppm ibuprofen, which achieved an average plasma concentration of ibuprofen lower than the peak level achieved in humans at therapeutic doses, inhibited tumor growth by 40% to 82%. Fewer liver metastases were found in the ibuprofen group compared with the control group. In combination therapy with the standard antineoplastic agents, 5-fluorouracil, or irinotecan (CPT-11), tumor volumes in the groups with ibuprofen +/- CPT-11 or 5-fluorouracil were smaller than in the control group. Ibuprofen was similar to the cyclooxygenase-2 selective inhibitor rofecoxib in its ability to suppress tumor growth and improve overall survival. CONCLUSIONS: Ibuprofen, in part by modulating tumor angiogenesis, decreases both tumor growth and metastatic potential in mice. The ibuprofen doses were in the low range of therapeutic human plasma concentrations. Ibuprofen potentiates the antitumor properties of CPT-11 and improves survival of mice without increasing gastrointestinal toxicity.

Animals↗

Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients.

PURPOSE: ERCC1 is a lead enzyme in the nucleotide excision repair pathway of DNA repair. Polymorphisms have been identified in the ERCC1 gene, the C8092A and codon 118 polymorphisms, which may lead to an altered capacity to regenerate damaged normal tissue and greater treatment-related toxicity. EXPERIMENTAL DESIGN: Using logistic regression models, we evaluated the ERCC1 C8092A and codon 118 polymorphisms and their association with the occurrence of grade 3 or 4 toxicity in 214 stage III and IV non-small cell lung cancer patients treated first line with platinum-based chemotherapy. Adjusting covariates were performance status and type of treatment regimen. RESULTS: There was no statistically significant association between either the C8092A or codon 118 polymorphism and overall or hematologic grade 3 or 4 toxicity. However, carrying at least one variant ERCC1 C8092A allele was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (adjusted odds ratio, 2.33; 95% confidence interval, 1.07-5.05; P = 0.03). CONCLUSIONS: Adjusting for performance status and type of treatment regimen, carrying at least one ERCC1 8092A allele is associated with a >2-fold increase in grade 3 or 4 gastrointestinal toxicity among platinum-treated non-small cell lung cancer patients.

Adult↗

Ginsenosides block HIV protease inhibitor ritonavir-induced vascular dysfunction of porcine coronary arteries.

Human immunodeficiency virus (HIV) protease inhibitor ritonavir (RTV) may induce vascular dysfunction through oxidative stress. Ginsenosides have been shown to have potential benefits on the cardiovascular system through diverse mechanisms, including antioxidative property. The objective of this study was to determine whether ginsenosides could prevent coronary arteries from RTV-induced dysfunction. Porcine coronary artery rings were incubated with RTV and ginsenosides Rb1, Rc, and Re for 24 h. Vasomotor function was recorded by a myograph tension system. In response to the thromboxane A(2) analog U-46619, the contraction of the vessel rings was significantly reduced. When cocultured with Rb1, Rc, and Re, the contractility significantly increased. In response to bradykinin at 10(-5) M, the endothelium-dependent relaxation of vessel rings was significantly reduced by 59% for RTV compared with controls (P < 0.05). When cocultured with Rb1, Rc, and Re, the relaxation significantly increased 100%, 90%, and 134%, respectively, compared with the RTV-alone groups (P > 0.05). In response to sodium nitroprusside, RTV significantly reduced vasorelaxation. In addition, the endothelial nitric oxide synthase (eNOS) mRNA levels were significantly reduced by 78% for RTV group (P < 0.05) by real-time PCR analysis. The eNOS protein levels measured by Western blot analysis and nitrite concentrations measured by Griess assay were also decreased, whereas O(2)(-) production by lucigenin-enhanced chemiluminescence was significantly increased in the RTV-treated group. These effects of RTV were effectively blocked by ginsenosides. Thus HIV protease inhibitor RTV significantly impaired the vasomotor function of porcine coronary arteries. This effect may be mediated by the downregulation of eNOS and overproduction of O(2)(-). These results suggest that ginsenosides can effectively block RTV-induced vascular dysfunction.

Animals↗

Induction of specific human primary immune responses to a Semliki Forest virus-based tumor vaccine in a Trimera mouse model.

Recombinant Semliki Forest virus (rSFV) enables high-level, transient expression of heterologous proteins in vivo, and is believed to be a superior vector for genetic vaccination, compared with the conventional DNA plasmid. Nonetheless, the efficacy of rSFV-based vaccine in eliciting human immune responses has not been tested. We used a Trimera mouse model, consisting of lethally irradiated BALB/c host reconstituted with nonobese diabetes/severe combined immunodeficiency (NOD/SCID) bone marrow plus human peripheral blood mononuclear cells (PBMCs), to characterize the in vivo immune responses against rSFV-encoded human melanoma antigen MAGE-3. MAGE-3-specific antibody and cytotoxic T lymphocyte (CTL) activity were detected by ELISA and 51Cr-release assay, respectively, and the responses were compared with those induced by a plasmid DNA vaccine encoding the same antigen. The results showed that rSFV vaccine could elicit human MAGE-3-specific antibody and CTL response in the Trimera mice, and the antitumor responses were more potent than those by plasmid DNA vaccination. This is the first report to evaluate human immune responses to an rSFV-based tumor vaccine in the Trimera mouse model. Our data suggest that rSFV vector is better than DNA plasmid in inducing protective immunity, and the Trimera model may serve as a general tool to evaluate the efficacy of tumor vaccines in eliciting human primary immune response in vivo.

Animals↗

Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells.

Class switch recombination (CSR) is a region-specific, transcriptionally regulated, nonhomologous recombinational process that is initiated by activation-induced cytidine deaminase (AID). The initial lesions in the switch (S) regions are subsequently processed and resolved, leading to recombination of the two targeted S regions. The mechanisms by which repair and ligation of the broken DNA ends occurs is still elusive. Recently, a small number of patients lacking DNA ligase IV, a critical component of the nonhomologous end joining (NHEJ) machinery, have been identified. We show that these patients display a considerably increased donor/acceptor homology at Smu-Salpha junctions compared with healthy controls. In contrast, Smu-Sgamma junctions show an increased frequency of insertions but no increase in junctional homology. These altered patterns of junctional resolution may be related to differences in the homology between the Smu and the downstream isotype S regions, and could reflect different modes of switch junction resolution when NHEJ is impaired. These findings link DNA ligase IV, and thus NHEJ, to CSR.

Base Sequence↗

Identification of a novel small-molecule inhibitor of the hypoxia-inducible factor 1 pathway.

Hypoxia-inducible factor 1 (HIF-1) is the central mediator of cellular responses to low oxygen and has recently become an important therapeutic target for solid tumor therapy. Inhibition of HIF-1 is expected to result in the attenuation of hypoxia-inducible genes, which are vital to many aspects of tumor biology, including adaptative responses for survival under anaerobic conditions. To identify small molecules inhibiting the HIF-1 pathway, we did a biological screen on a 10,000-membered natural product-like combinatorial library. The compounds of the library, which share a 2,2-dimethylbenzopyran structural motif, were tested for their ability to inhibit the hypoxic activation of an alkaline phosphatase reporter gene under the control of hypoxia-responsive elements in human glioma cells. This effort led to the discovery of 103D5R, a novel small-molecule inhibitor of HIF-1alpha. 103D5R markedly decreased HIF-1alpha protein levels induced by hypoxia or cobaltous ions in a dose- and time-dependent manner, whereas minimally affecting global cellular protein expression levels, including that of control proteins such as HIF-1beta, IkappaBalpha, and beta-actin. The inhibitory activity of 103D5R against HIF-1alpha was clearly shown under normoxia and hypoxia in cells derived from different cancer types, including glioma, prostate, and breast cancers. This inhibition prevented the activation of HIF-1 target genes under hypoxia such as vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1). Investigations into the molecular mechanism showed that 103D5R strongly reduced HIF-1alpha protein synthesis, whereas HIF-1alpha mRNA levels and HIF-1alpha degradation were not affected. 103D5R inhibited the phosphorylation of Akt, Erk1/2, and stress-activated protein kinase/c-jun-NH(2)-kinase, without changing the total levels of these proteins. Further studies on the mechanism of action of 103D5R will likely provide new insights into its validity/applicability for the pharmacologic targeting of HIF-1alpha for therapeutic purposes.

Benzopyrans↗

[Clinical experience of percutaneous endoscopic gastrostomy, jejunostomy, duodenostomy in 120 patients].

OBJECTIVE: To report clinical experience of percutaneous endoscopic gastrostomy, duodenostomy, jejunostomy in 120 patients, focusing on its technique and indications. METHODS: One hundred and twenty patients received percutaneous endoscopic gastrostomy, duodenostomy, jejunostomy from May 2001 to April 2004, including 75 percutaneous endoscopic gastrostomy (PEG), 42 percutaneous endoscopic jejunostomy (PEJ), 2 percutaneous endoscopic duodenostomy (PED), 1 direct percutaneous endoscopic jejunostomy (DPEJ). All tubes established by traditional pull technique. RESULTS: The average duration of PEG was (9 +/- 4) min, PEJ (17 +/- 6) min, DPEJ 20 min, and PED was 10 and 12 min for 2 patients, respectively. Success rate of the technique was 98.4% (120/122). Major complication rate was 0.8% (1/120), and minor complication rate was 7.5% (9/120). Clinical indications: PEG, PED and PEJ were applied for long-term enteral nutritional support in 88 patients, gastrointestinal decompression in 25 patients, and transfusing external drainage bile to gastrointestinal tract in 5 patients. Two radiation enteritis patients used PEG for gastrointestinal decompression preoperatively and long-term enteral nutritional support postoperatively. CONCLUSION: PEG, PED PEJ and DPEJ are easily handled, effective and safe, and may be widely used in clinical practice.

Adult↗

Cross-presentation of phage particle antigen in MHC class II and endoplasmic reticulum marker-positive compartments.

It has been shown that exogenous antigens can access the MHC class I pathway of professional antigen-processing cells. However, details as to how the MHC class I-peptide complex forms in the presentation pathway are still poorly understood. Here we used MHC class I-peptide-specific antibodies to investigate the formation and intracellular location of class I-peptide complexes in macrophages. We observed that the formation of class I-peptide complexes occurs within a few hours and lasts for another few hours on the cell surface of macrophages following loading with filamentous phage particles. The class I-peptide complexes in the process were co-localized with MHC class II molecules and endocytic system markers. Moreover, endosomal compartments containing class I-peptide complexes were found within intracellular organelles stained by DiOC6 and calnexin. In addition, the cross-presentation of phage particles was transporter associated with antigen processing (TAP)-dependent and sensitive to proteasome inhibitors and NH(4)Cl. These data suggest that endocytosed phage particles may be processed and cross-presented in organelles positive for phagosome and endoplasmic reticulum (ER) markers via a classical ER MHC class I loading mechanism.

Ammonium Chloride↗

Deoxyribozymes inhibit the expression of period1 gene in vitro.

To investigate the effect of two deoxyribozymes targeting period1 (per1) mRNA in vitro for exploring a novel gene therapy approach about circadian rhythm diseases, the specific deoxyribozymes targeting per1 were designed and synthesized chemically following MFold analysis according to its mRNA secondary structure. per1 RNA fragments were prepared by in vitro transcription of pcDNA3.1(+)-per1(164:256). The cleavage reactions containing deoxyribozymes and per1 RNA fragments were performed under certain conditions. With the transfection technique mediated by LipofectAMINE, pcDNA3-per1 and DRz164 or DRz256 were introduced into NIH3T3 cells. The effects of deoxyribozymes on per1 were studied by reverse transcript-polymerase chain reaction (RT-PCR) and flow cytometry (FCM). When deoxyribozymes and RNA transcripts were incubated under the adopted conditions at 37 degrees C for 2 h, about 63% of per1(164:256) RNA transcripts were cleaved by DRz164 and about 50.5% by DRz256. After cotransfecting pcDNA3-per1 with DRz164 or DRz256, the expression of per1 mRNA was decreased, as indicated by RT-PCR semi-quantity analysis. FCM analysis showed that Per1 protein was inhibited. Both DRz164 and DRz256 targeting per1 have the specific cleavage activity toward per1 mRNA in vitro and can highly block the expression of per1 gene in cellular milieu.

Animals↗

A comparison of carotid artery stenting with neuroprotection versus carotid endarterectomy under local anesthesia.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke in patients with high-grade carotid artery stenosis. Despite the known impact of type of anesthesia on outcome after CEA, none of the current studies comparing CEA with CAS addresses the effect of anesthetic choice on perioperative events. In this study, we compare our results of distally protected CAS versus CEA under local anesthesia. METHODS: Clinical data of 345 patients who underwent 372 procedures for carotid artery occlusive disease over a 36-month were retrospectively collected for this analysis. Distal embolic protection was used in CAS procedures. All procedures, both CEA (n = 221, 59%) and CAS (N = 152, 41%), were performed under local anesthesia. The primary outcome measure was aggregate 30-day major ipsilateral stroke and/or death. Follow-up serial Duplex ultrasound examinations were performed. RESULTS: Both patient cohorts were similar in terms of demographic and risk factors, with the exception of a higher incidence of coronary artery disease in the CAS group (59% versus 30%, P <.05). The 30-day stroke and death rates were 3.2% (CAS) and 3.7% (CEA) (P = not significant). Cranial nerve injury only occurred in the CEA patients (2.3%). Perioperative hemodynamic instability was more common among patients in the CAS group (11.9% versus 4.1%, P <.05). CONCLUSIONS: Percutaneous carotid stenting with neuroprotection provides comparable clinical success to CEA performed under local anesthetic. Further studies are warranted to validate the long-term efficacy of CAS and to elucidate patient selection criteria for endovascular carotid revascularization.

Aged↗

Carotid artery stenting with neuroprotection: assessing the learning curve and treatment outcome.

PURPOSE: Carotid artery stenting (CAS) has emerged as an acceptable treatment alternative in high-risk patients with carotid stenosis. The purpose of this study was to assess the effect of the learning curve on treatment complications and the clinical outcomes of CAS. METHODS: Clinical variables and treatment outcomes of 200 consecutive CAS procedures in 182 patients (mean age 72 years) with carotid stenosis > or = 70% during a 40-month period were analyzed. Four sequential groups (groups I, II, III, and IV) of 50 consecutive interventions were compared with regard to technical success, periprocedural complications, and treatment outcomes. RESULTS: Treatment indications and relevant risk factors were similar among the 4 groups. The overall technical success and combined 30-day stroke and death rates were 98% and 2.5%, respectively. An increase in the technical success rate was noted in the latter 3 groups compared with group I (P < .05). Total procedural time and contrast volume were significantly higher in group I compared with the latter 3 groups (P < .05). The intraoperative anticoagulation regimen was changed from intravenous heparin combination to bivalirudin after the first 54 patients, which resulted in decreased bleeding complications in groups III and IV (P = 0.03) compared with the first group. The 30-day stroke and death rate in groups I and II were 8% and 2%, respectively, and was decreased significantly in groups III and IV (0% and 0%, respectively, P < .05). A Cox regression model identified procedural volume (P = .03) as a predictor of decreased complication rate. CONCLUSIONS: CAS with neuroprotection can provide excellent treatment outcomes. Our experience demonstrates a procedure-associated learning curve as evidenced by decreased procedure-related complications, fluoroscopic time, and contrast volume occurring with increased physician experience. Procedural success was also enhanced partly by endovascular device refinement and an improved anticoagulation regimen. Successful CAS outcomes can be achieved once physicians overcome the initial procedure-related learning curve.

Aged↗

Ginsenoside Rb1 blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries.

OBJECTIVE: Homocysteine (Hcy) is an independent risk factor for atherosclerosis. This study investigates the effects of ginsenoside Rb1, a major constituent of ginseng, on Hcy-induced endothelial dysfunction and molecular changes in porcine coronary arteries. METHODS: The coronary arteries were harvested from pig hearts and cut into 5-mm ring segments, which were then divided into six groups, including control, Hcy alone (50 microM), low-dose (1 microM) or high-dose (10 microM) Rb1 alone, and Hcy plus low-dose or high-dose Rb1. After 24-hour incubation, the rings were analyzed for vasomotor function in response to thromboxane A2 analog U46619, bradykinin, and sodium nitroprusside (SNP), respectively. In addition, superoxide anion was assessed by lucigenin-enhanced chemiluminescence analysis. Endothelial nitric oxide synthase (eNOS) was studied using real-time polymerase chain reaction and Western blot. RESULTS: Endothelium-dependent relaxation (bradykinin) was significantly reduced in rings treated with Hcy alone as compared with the control (49.80% vs 71.77%, n = 8, P < .05), whereas neither high-dose nor low-dose Rb1 alone affected the endothelium-dependent relaxation. The low-dose Rb1-Hcy combined group had a partially improved endothelium-dependent relaxation (54.44%), whereas the high-dose Rb1-Hcy combined group showed a complete recovery of endothelium-dependent relaxation (72.89%). There was no substantial difference in maximal contraction induced by U46619 or endothelium-independent relaxation by SNP among all groups (P > .05). Furthermore, superoxide anion was markedly increased by 137% in the Hcy-treated group as compared with the control, but there were no statistically significant changes from the control in all other groups (P > .05). Lastly, eNOS mRNA and protein levels were substantially reduced in the Hcy-treated group, but not in the Rb1-Hcy combined groups. CONCLUSIONS: This is the first study to show that ginsenoside Rb1 can effectively block Hcy-induced endothelial dysfunction and superoxide anion production as well as eNOS downregulation in porcine coronary arteries. This study suggests that ginseng and its active constituents may have potential clinical applications in controlling Hcy-associated vascular injuries. CLINICAL RELEVANCE: Homocysteine (Hcy) is an independent risk factor for atherosclerosis and other vascular lesions. It causes endothelial dysfunction and oxidative stress. Ginseng compounds have effects of vasorelaxation and antioxidation. The purpose of this study was to determine the effect of ginsenoside Rb1, a major constituent of ginseng, on Hcy-induced endothelial dysfunction and molecular changes in porcine coronary arteries. Our results showed that ginsenoside Rb1 can effectively block Hcy-induced dysfunction of endothelium-dependent vasorelaxation as well as superoxide anion production and eNOS downregulation. This study suggests that ginseng compounds may have potential clinical applications in controlling Hcy-associated vascular diseases and other vascular lesions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Bacillus nematocida sp. nov., a novel bacterial strain with nematotoxic activity isolated from soil in Yunnan, China.

An endospore-forming bacterium, designated strain B-16T, was isolated from a forest soil sample in Yunnan, China. The isolate presented remarkable nematotoxic activity against nematode Panagrellus redivivus. The organism was strictly aerobic, motile, spore forming and rod shaped, catalase- and oxidase-positive. The predominant isoprenoid quinone was menaquinone 7 (MK-7). The major cellular fatty acid profiles were anteiso-C15:0 (48.67%), iso-C15:0 (13.45%), C16:0 (9.06%) and anteiso-Cl7:0 (8.29%). The DNA G+C content was 46%. Phylogenetic analyses based on 16S rDNA sequence revealed that isolate belongs to the genus Bacillus. Strain B-16T exhibited high 16S rDNA similarity with its closest neighbors Bacillus vallismortis (99.79%), B. subtilis (99.43%), B. atrophaeus (99.43%), B. amyloliquefaciens (99.36%), B. licheniformis (98.0%) and less than 97.0% with all the other relative type strains in the genus Bacillus. The phenotypic and genotypic characteristics and DNA-DNA relatedness data indicate that strain B-16T should be distinguished from all the relative species of genus Bacillus. Therefore, on the basis of the polyphasic taxonomic data presented, a new species of the genus Bacillus, B. nematocida, with the type strain B-16T ( = CGMCC 1128T) is proposed. The GenBank accession number for the sequence reported in this paper is AY820954.

Aerobiosis↗

The case for thrombolysis for iliofemoral venous thrombosis.

Deep venous thrombosis and its consequences remain a significant clinical challenge despite advances in the current healthcare system. The use of thrombolytic therapy has played an important role in the management of both arterial and venous thrombotic conditions. In this article, relevant clinical evidence and rationale in support of thrombolytic therapy in ileofemoral deep venous thrombosis are discussed.

Angioplasty↗

Molecular epidemiology of non-small cell lung cancer.

Although smoking is the primary risk factor for most lung cancers, genetic predisposition may play an important role. Familial aggregation studies suggest a greater genetic component in the risk for younger individuals developing lung cancer, for lifetime nonsmokers, and possibly for women. Low-penetrance, high-prevalence polymorphic genes may explain part of this genetic predisposition. Functional polymorphisms of xenobiotic metabolism may alter the total exposure of tobacco carcinogens in the host. Subtle alterations in the DNA repair, inflammatory, and cell cycle pathways may also alter lung cancer susceptibility. The role of individual polymorphisms has been evaluated for several genes including the CYP and glutathione s-transferase superfamilies, and the NAT genes; DNA repair genes such as XPD (nucleotide excision pathway), XRCC1 (base excision pathway), and MGMT; and tumor suppressor or cell cycle genes such as p53. Molecular epidemiological studies are now focused on building larger databases from existing smaller studies and developing strategies to simultaneously evaluate multiple polymorphisms and genes within the same pathway.

Carcinoma, Non-Small-Cell Lung↗

Dietary iron, zinc, and calcium and the risk of lung cancer.

BACKGROUND: Iron, zinc, and calcium are all involved in the metabolism of reactive oxygen species and may compete with each other for similar binding sites. Dietary intakes of these micronutrients have been associated with altered risks of colorectal, breast, and prostate cancers. METHODS: In this Massachusetts hospital-based case-control study of 923 patients with lung cancer and 1125 healthy controls, we studied the associations between dietary iron, zinc, and calcium intake and the risk of lung cancer. Dietary intake was assessed at the time of recruitment (1992 to 2000) with the use of a 126-item semiquantitative food-frequency questionnaire. We analyzed the data using multiple logistic regression models adjusting for smoking history and other potential risk factors. RESULTS: The adjusted odds ratios of dietary iron, zinc, and calcium from food sources were 1.45 (95% confidence interval=1.03-2.06), 0.71 (0.50-0.99), and 1.64 (1.17-2.29), respectively, for the highest quintile versus the lowest quintile of each micronutrient. Stronger associations between micronutrients and lung cancer risk were found when iron, zinc, and calcium were included together in the same model. The associations between dietary micronutrients intake and lung cancer risk were stronger among current smokers than among former smokers. When we examined intake from supplements as well as diet, associations were similar to those for diet alone. CONCLUSIONS: Dietary iron, zinc, and calcium may play an important role in the development of lung cancer, especially among current smokers. These results need to be confirmed in large prospective studies.

Adult↗