Tianjin Tianhe Hospital

Although flexible humidity sensors are essential for human health monitoring, it is still challenging to achieve high sensitivity and easy disposal with simple, low-cost fabrication processes. This study presents the design and fabrication of highly reliable hand-drawn interdigital electrodes from pencil-on-paper treated with NaCl solution for highly sensitive hydration sensors working over a wide range of relative humidity (RH) levels from 5.6% to 90%. The applications of the resulting flexible humidity sensor go beyond the monitoring of respiratory rate and proximity to characterizations of human skin types and evaluations of skin barrier functions through insensible sweat measurements. The sensor array can also be integrated with a diaper to result in smart diapers to alert for an early diaper change. The design and fabrication strategies presented in this work could also be leveraged for the development of wearable, self-powered, and recyclable sensors and actuators in the future.

Abstract A “green” processing method, dual‐melt extrusion, was used to prepare thermoplastic starch/montmorillonite nanocomposites without organic reactions in the solution. XRD demonstrates that sorbitol enlarged the interlayer distance of MMT during the first step. MMT‐sorbitol, formamide and starch were used to obtain TPS/MMT nanocomposites in the second step. XRD and TEM reveal that TPS intercalated the layers of MMT. With increasing MMT content, improvements in thermal stability, tensile strength, Young's modulus and energy break, and a slight decrease of elongation at break, appeared. The effect of water content on the tensile strength and elongation at break was also studied. magnified image

Abstract Monitoring nitrogen utilization efficiency and soil temperature in agricultural systems for timely intervention is essential for crop health with reduced environmental pollution. Herein, this work presents a high‐performance multi‐parameter sensor based on vanadium oxide (VO X )‐doped laser‐induced graphene (LIG) foam to completely decouple nitrogen oxides (NO X ) and temperature. The highly porous 3D VO X ‐doped LIG foam composite is readily obtained by laser scribing vanadium sulfide (V 5 S 8 )‐doped block copolymer and phenolic resin self‐assembled films. The heterojunction formed at the LIG/VO X interface provides the sensor with enhanced response to NO X and an ultralow limit of detection of 3 ppb (theoretical estimate of 451 ppt) at room temperature. The sensor also exhibits a wide detection range, fast response/recovery, good selectivity, and stability over 16 days. Meanwhile, the sensor can accurately detect temperature over a wide linear range of 10–110 °C. The encapsulation of the sensor with a soft membrane further allows for temperature sensing without being affected by NO X . The unencapsulated sensor operated at elevated temperature removes the influences of relative humidity and temperature variations for accurate NO X measurements. The capability to decouple nitrogen loss and soil temperature paves the way for the development of future multimodal decoupled electronics for precision agriculture and health monitoring.

CONTEXT: Living in a prediabetes state significantly increases a patient's risk for both diabetes and cardiovascular disease. Tianqi capsule, containing 10 Chinese herbal medicines, is used in China for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE: The purpose of this study was to assess whether Tianqi prevented T2DM in subjects with impaired glucose tolerance (IGT) over the course of a 12-month treatment. METHODS: Individuals with IGT were randomly allocated in a double-blind manner to receive Tianqi (n = 210) or a placebo (n = 210) for 12 months. Oral glucose tolerance tests were conducted every 3 months to assess the development of diabetes or restoration to normal glucose tolerance. All subjects received the same lifestyle education. The primary endpoint was the conversion of IGT to T2DM. Body weight and body mass index were observed. Adverse effects were monitored. RESULTS: Of the 420 enrolled subjects with IGT, 389 completed the trial (198 in the Tianqi group and 191 in the placebo group). At the end of the 12-month trial, 36 subjects in the Tianqi group (18.18%) and 56 in the placebo group (29.32%) had developed diabetes (P = .01). There was a significant difference in the number of subjects who had normal glucose tolerance at the end of the study between the Tianqi and placebo groups (n = 125, 63.13%, and n = 89, 46.60%, respectively; P = .001). Cox's proportional hazards model analysis showed that Tianqi reduced the risk of diabetes by 32.1% compared with the placebo. No severe adverse events occurred in the trial. There were no statistical differences in body weight and body mass index changes between the Tianqi group and the placebo group during the 12-month trial. CONCLUSIONS: Treatment with a Tianqi capsule for 12 months significantly decreased the incidence of T2DM in subjects with IGT, and this herbal drug was safe to use.

PARP inhibitors have been approved for the therapy of cancers with homologous recombination (HR) deficiency based on the concept of "synthetic lethality". However, glioblastoma (GBM) patients have gained little benefit from PARP inhibitors due to a lack of BRCA mutations. Herein, we demonstrated that concurrent treatment with the PARP inhibitor rucaparib and the PI3K inhibitor BKM120 showed synergetic anticancer effects on GBM U251 and U87MG cells. Mechanistically, BKM120 decreased expression of HR molecules, including RAD51 and BRCA1/2, and reduced HR repair efficiency in GBM cells, therefore increasing levels of apoptosis induced by rucaparib. Furthermore, we discovered that the two compounds complemented each other in DNA damage response and drug accumulation. Notably, in the zebrafish U87MG-RFP orthotopic xenograft model, nude mouse U87MG subcutaneous xenograft model and U87MG-Luc orthotopic xenograft model, combination showed obviously increased antitumor efficacy compared to each monotherapy. Immunohistochemical analysis of tumor tissues indicated that the combination obviously reduced expression of HR repair molecules and increased the DNA damage biomarker γ-H2AX, consistent with the in vitro results. Collectively, our findings provide new insight into combined blockade of PI3K and PARP, which might represent a promising therapeutic approach for GBM.

BACKGROUND: A few studies have examined the association between ambient temperature and preterm birth (PTB), and the results have been inconsistent. This study explored the association between ambient temperature and PTB in Shenzhen, China. METHODS: Data of daily singleton PTB, air pollution and meteorological variables from 2005 to 2011 were collected in Shenzhen. A distributed lag non-linear model (DLNM) was used to investigate the association of the low and high temperatures (1st, 5th, 95th, and 99th percentiles) with PTB. RESULTS: The median temperature was 24.5 °C and the 1st, 5th, 95th, and 99th percentiles of daily mean temperatures were 9, 12.5, 29.9 and 30.7 °C, respectively. The prevalence of singleton PTB was 5.61 % in Shenzhen. The association between temperature and PTB was not linear. There was an immediate positive association of low temperature (1st and 5th percentiles) and a negative association of high temperature (95th and 99th percentiles) with PTB. The effect of low temperature 9 °C (1st) on PTB on the current day was stronger than that of 12.5 °C (5th), with a relative risk (RR) of 1.54 (95 % CI: 1.36-1.75) and 1.49 (95 % CI: 1.35-1.63), respectively. The cumulative RR (up to 30 days) of 9 and 12.5 °C was 1.72 (95 % CI: 1.28-2.33) and 1.96 (95 % CI: 1.60-2.39), respectively. The cumulative effects (up to 30 days) of high temperature (95th and 99th percentiles) on PTB were 0.69 (95 % CI: 0.60-0.80) and 0.62 (95 % CI: 0.52-0.74), respectively. The cumulative effect (up to 30 days) of low temperatures on vaginal delivery PTB was lower than that of the cesarean section PTB with an RR of 1.58 (95 % CI: 1.12-2.22) and 1.93 (95 % CI: 1.21-3.08), respectively. CONCLUSIONS: This study suggests that low temperature might be a risk factor, while high temperature might be a protective factor of PTB in Shenzhen.

Crumb rubber is a material produced by shredding and commutating used tires. There is no doubt that the increasing piles of used tires create environmental concerns. The long-term goal of this research is to find means to dispose of the crumb rubber by placement of the rubber in portland cement concrete and still provide a final product with good engineering properties. The Arizona Department of Transportation and Arizona State University have initiated several crumb rubber concrete (CRC) test sections throughout Arizona over the past few years. Laboratory tests were conducted to support the knowledge learned in the field and enhance the understanding of the material properties of CRC. Concrete laboratory tests included compressive, flexural, indirect tensile strength, thermal coefficient of expansion, and microscopic matrix analyses. The unit weight and the compressive and flexural strengths decreased as the rubber content in the mix increased. Further investigative efforts determined that the entrapped air, which caused excessive reductions in compressive strength, could be reduced substantially by adding a deairing agent. The higher tensile strains at failure observed from the tests were indicative of more ductile, energy-absorbent mix behavior. The coefficient of thermal expansion test results indicated that CRC was more resistant to thermal changes. The CRC specimens tested remained intact after failure and did not shatter as a conventional mix did. Such behavior may be beneficial for a structure that requires good impact resistance properties. If no special considerations are made to maintain higher strength values, the use of CRC mixes in places where high-strength concrete is not required is recommended.

Do firms always choose the cheapest suitable inputs, or can group attitudes affect their choices? To investigate this question, we examine the deterioration of relations between the United States and France from 2002–2003, when France's favorability rating in the US fell by 48 percentage points. We estimate that the worsening attitudes reduced bilateral trade by about 9 percent and that trade in inputs probably declined similarly, by about 8 percent. We use these estimates to calculate the average decrease in firms' willingness to pay for French (or US) commodities when attitudes worsened. (JEL D24, F13, F14, L14, L21)

We found previously that short-term curcumin gavage stimulated mouse hepatic fibroblast growth factor 21 (Fgf21) expression. Here we conducted mechanistic exploration and investigated the potential pathophysiological relevance on this regulation. Fgf21 stimulation was observed at messenger RNA and protein levels in mice with daily curcumin gavage for 4 or 8 days and in primary hepatocytes with curcumin treatment. Using peroxisome proliferator-activated receptor α (PPARα) agonist and antagonist, along with luciferase reporter and chromatin immune-precipitation approaches, we determined that curcumin stimulates Fgf21 transcription in a mechanism involving PPARα activation. High-fat diet (HFD) feeding also increased mouse hepatic and serum Fgf21 levels, whereas dietary curcumin intervention attenuated these increases. We found that HFD feeding reduced hepatic expression levels of genes that encode FGFR1 and βKlotho, PGC1α, and the targets of the PPARα-PGC1α axis, whereas concomitant curcumin intervention restored or partially restored their expression levels. Importantly, hepatocytes from HFD-fed mice showed a loss of response to FGF21 treatment on Erk phosphorylation and the expression of Egr1 and cFos; this response was restored in hepatocytes from HFD-fed mice with curcumin intervention. This investigation expanded our mechanistic understanding of the metabolic beneficial effects of dietary curcumin intervention involving the regulation of Fgf21 production and the attenuation of HFD-induced Fgf21 resistance.

signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

BACKGROUND: The critical role of phosphoinositide 3-kinase (PI3K) activation in tumor cell biology has prompted massive efforts to develop PI3K inhibitors (PI3Kis) for cancer therapy. However, recent results from clinical trials have shown only a modest therapeutic efficacy of single-agent PI3Kis in solid tumors. Targeting autophagy has controversial context-dependent effects in cancer treatment. As a FDA-approved lysosomotropic agent, hydroxychloroquine (HCQ) has been well tested as an autophagy inhibitor in preclinical models. Here, we elucidated the novel mechanism of HCQ alone or in combination with PI3Ki BKM120 in the treatment of cancer. METHODS: The antitumor effects of HCQ and BKM120 on three different types of tumor cells were assessed by in vitro PrestoBlue assay, colony formation assay and in vivo zebrafish and nude mouse xenograft models. The involved molecular mechanisms were investigated by MDC staining, LC3 puncta formation assay, immunofluorescent assay, flow cytometric analysis of apoptosis and ROS, qRT-PCR, Western blot, comet assay, homologous recombination (HR) assay and immunohistochemical staining. RESULTS: HCQ significantly sensitized cancer cells to BKM120 in vitro and in vivo. Interestingly, the sensitization mediated by HCQ could not be phenocopied by treatment with other autophagy inhibitors (Spautin-1, 3-MA and bafilomycin A1) or knockdown of the essential autophagy genes Atg5/Atg7, suggesting that the sensitizing effect might be mediated independent of autophagy status. Mechanistically, HCQ induced ROS production and activated the transcription factor NRF2. In contrast, BKM120 prevented the elimination of ROS by inactivation of NRF2, leading to accumulation of DNA damage. In addition, HCQ activated ATM to enhance HR repair, a high-fidelity repair for DNA double-strand breaks (DSBs) in cells, while BKM120 inhibited HR repair by blocking the phosphorylation of ATM and the expression of BRCA1/2 and Rad51. CONCLUSIONS: Our study revealed that HCQ and BKM120 synergistically increased DSBs in tumor cells and therefore augmented apoptosis, resulting in enhanced antitumor efficacy. Our findings provide a new insight into how HCQ exhibits antitumor efficacy and synergizes with PI3Ki BKM120, and warn that one should consider the "off target" effects of HCQ when used as autophagy inhibitor in the clinical treatment of cancer.

BACKGROUND: The mix of physical therapy services is thought to be different with different impairment groups. However, it is not clear how much variation there is across impairment groups. Furthermore, the extent to which the same physical therapy activities are associated with functional outcomes across different types of patients is unknown. OBJECTIVE: The purposes of this study were: (1) to examine similarities and differences in the mix of physical therapy activities used in rehabilitation among patients from different impairment groups and (2) to examine whether the same physical therapy activities are associated with functional improvement across impairment groups. DESIGN: This was a prospective observational cohort study. METHODS: The study was conducted in inpatient rehabilitation facilities. The participants were 433 patients with stroke, 429 patients with total knee arthroplasty (TKA), and 207 patients with traumatic brain injury (TBI). Measures used in this study included: (1) the Comprehensive Severity Index to measure the severity of each patient's medical condition, (2) the Functional Independence Measure (FIM) to measure function, and (3) point-of-care instruments to measure time spent in specific physical therapy activities. RESULTS: All 3 groups had similar admission motor FIM scores but varying cognitive FIM scores. Patients with TKA spent more time on exercise than the other 2 groups (average=31.7 versus 6.2 minutes per day). Patients with TKA received the most physical therapy (average=65.3 minutes per day), whereas the TBI group received the least physical therapy (average=38.3 minutes per day). Multivariate analysis showed that only 2 physical therapy activities (gait training and community mobility) were both positively associated with discharge motor FIM outcomes across all 3 groups. Three physical therapy activities (assessment time, bed mobility, and transfers) were negatively associated with discharge motor FIM outcome. LIMITATIONS: The study focused primarily on physical therapy without concurrently considering other therapies such as occupational therapy, speech-language pathology, nursing care, and case management or the potential interaction of these inputs. This analysis did not consider the interventions that physical therapists used when patients participated in discrete physical therapy activities. CONCLUSIONS: All 3 patient groups spent a considerable portion of their physical therapy time in gait training relative to other activities. Both gait training and community mobility are higher-level activities that were positively associated with outcomes, although all 3 groups spent little time in community mobility activities. Further research studies, such as randomized clinical trials and predictive validity studies, are needed to investigate whether higher-level or more-integrated therapy activities are associated with better patient outcomes.

Summary This paper studies finite‐time fully distributed formation and reconfiguration control of multiple unmanned aerial vehicle helicopter with disturbances and uncertainty. Based on adaptive and terminal sliding‐mode control techniques, a disturbance observer‐based fully distributed control strategy is proposed, which is independent of least nonzero eigenvalue of Laplacian matrix and achieves practical finite‐time formation tracking for a moving leader without any additional condition. The proposed method is proved superior to the existing method in converging time. The finite‐time stability of the closed‐loop error is proved by the Lyapunov theory. Considering formation configuration changing as a result of a task change, a modified finite‐time fully distributed controller including potential energy function gradient terms with an adaptive law is proposed. The novelty of the reconfiguration controller is that an adaptive law is firstly integrated in the gradient items, then the asymptotical stability is extended to practical finite‐time stability. Simulation results are presented to demonstrate the efficiency of the developed algorithm.

Chitosan can serve as a natural alternative to petroleum-based components in food packaging; however, the mechanical and barrier properties of pure chitosan film possess certain limitations. This paper presents a comprehensive review on the mechanical and barrier properties of composite films formed by combining chitosan-based films with plasticizers, polysaccharides, proteins, and lipids. These composite films often exhibit superior mechanical strength and enhanced barrier performance compared to pure chitosan film, thereby expanding the potential applications of chitosan in food packaging. Chitosan represents an ideal raw material for developing innovative biofilms that can cater to diverse packaging requirements for various food products while offering promising prospects for broad application.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is a natural functional component that has a variety of biological activities. The molecular structures and apoptosis-inducing activities on human hepatoma SMMC-7721 cells of two LBP fractions, LBP-d and LBP-e, were investigated. RESULTS: The results showed that LBP-d and LBP-e both consist of protein, uronic acid, and neutral sugars in different proportions. The structure of LBP was characterized by gas chromatography, periodate oxidation, and Smith degradation. LBP-d was composed of eight kinds of monosaccharides (fucose, ribose, rhamnose, arabinose, xylose, mannose, galactose, and glucose), while LBP-e was composed of six kinds of monosaccharides (fucose, rhamnose, arabinose, mannose, galactose, and glucose). LBP-d and LBP-e blocked SMMC-7721 cells at the G0/G1 and S phases with an inhibition ratio of 26.70 and 45.13%, respectively, and enhanced the concentration of Ca(2+) in the cytoplasm of SMMC-7721. CONCLUSION: The contents of protein, uronic acid, and galactose in LBP-e were much higher than those in LBP-d, which might responsible for their different bioactivities. The results showed that LBP can be provided as a potential chemotherapeutic agent drug to treat cancer.

A novel method has been established for the construction of C-S bonds using redox-active esters with disulfides in the presence of Ru-photoredox catalyst. This method exhibits remarkable functional group tolerance across a wide scope of substrates. Under mild conditions, a structurally diverse array of aryl alkyl sulfides is successfully and efficiently obtained through decarboxylative cross-coupling.

ABSTRACT Protamine, derived from fish milt, which is normally discarded as an industrial by-product in the process of fish plant, was hydrolyzed with pancreatin. Salmon protamine hydrolysate was found to possess antioxidative activity against hydroxyl, 2,2-diphenyl-1-picrylhydrazyl and superoxide anion radicals. Through consecutive chromatographic methods including size exclusion, ion exchange chromatography and reverse-phase high performance liquid chromatography (HPLC), a series of peptide fractions with high antioxidative activities were obtained. Peptide with highest antioxidative activity was identified to be Pro-Arg matching 1–2 and 16–17 residues of the salmon protamine by electrospray ionization mass spectrometry and database search. These results provided sufficient and scientific information for the marketing of health food supplemented with protamine hydrolysate and added further support for the wide applications of fish milt. PRACTICAL APPLICATIONS Protamine could be used to produce protamine hydrolysate with antioxidative activity. There are few reports on protamine hydrolysate as natural health food, especially its bioactive fraction. This work reports isolation and characterization of antioxidative peptides from protamine hydrolysate, which was derived from salmon milt. It is beneficial to utilize fish milt, which is readily available in large quantities and at low prices. Furthermore, the use of protamine hydrolysate in health food is gaining much more interest.

Therapeutic interference of the programmed cell death protein 1(PD-1)/immunosuppressive programmed cell death ligand 1 (PD-L1) signaling pathway by monoclonal antibodies has achieved spectacular success for treating various tumors. However, the development of small molecule inhibitors of PD-1/PD-L1 has lagged far behind due to the challenge of targeting the highly hydrophobic and relatively flat binding interface, despite the benefits small molecule can bring over therapeutic antibodies. This technical challenge provokes the adoption of different strategies in searching for small, medium-sized, and large molecule modulators (e.g., degraders, downregulators, and covalent inhibitors) of the PD-1/PD-L1 protein–protein interaction. In this review article, we discuss latest advances in the development of PD-L1 modulators, with a focus on degraders, downregulators, and covalent inhibitors.

A critical goal in transplantation is the achievement of donor-specific tolerance, minimizing the use of immunosuppressants. Dendritic cells (DCs) are antigen (Ag) presenting cells (APCs) with capability to promote immunity or tolerance. The immune-regulatory properties of DCs have been exploited for generation of tolerogenic/immunosuppressive (IS) DCs that, when transfer systemically, prolong allograft survival in murine models. Surprisingly, the in vivo mechanisms of therapies based on (donor- or recipient-derived) ISDCs in transplantation remain unknown, given that previous studies investigated their effects in vitro, or ex vivo after transplantation. Since once injected, ISDCs are short-lived and transfer Ag to recipient APCs, we assessed the role of recipient DCs by depleting them at the time of ISDC-therapy in a mouse model of cardiac transplantation. The results indicate that, contrary to the accepted paradigm, systemically administered ISDCs reduce the alloresponse and prolong allograft survival, not by themselves, but through conventional DCs (cDCs) of the recipient. These findings raise doubts on the advantages of the currently used ISDC-therapies, since the immune-regulatory properties of the injected ISDC do not seem to be functionally relevant in vivo, and the quiescent/pro-tolerogenic status of cDCs may be compromised in patients with end-stage diseases that require transplantation. A critical goal in transplantation is the achievement of donor-specific tolerance, minimizing the use of immunosuppressants. Dendritic cells (DCs) are antigen (Ag) presenting cells (APCs) with capability to promote immunity or tolerance. The immune-regulatory properties of DCs have been exploited for generation of tolerogenic/immunosuppressive (IS) DCs that, when transfer systemically, prolong allograft survival in murine models. Surprisingly, the in vivo mechanisms of therapies based on (donor- or recipient-derived) ISDCs in transplantation remain unknown, given that previous studies investigated their effects in vitro, or ex vivo after transplantation. Since once injected, ISDCs are short-lived and transfer Ag to recipient APCs, we assessed the role of recipient DCs by depleting them at the time of ISDC-therapy in a mouse model of cardiac transplantation. The results indicate that, contrary to the accepted paradigm, systemically administered ISDCs reduce the alloresponse and prolong allograft survival, not by themselves, but through conventional DCs (cDCs) of the recipient. These findings raise doubts on the advantages of the currently used ISDC-therapies, since the immune-regulatory properties of the injected ISDC do not seem to be functionally relevant in vivo, and the quiescent/pro-tolerogenic status of cDCs may be compromised in patients with end-stage diseases that require transplantation.

BACKGROUND: Nasopharyngeal carcinoma (NPC), also known as Cantonese cancer, is rare worldwide, but has particularly high incidence in North Africa and Southeast Asia, especially in Guangdong, China, such as Guangzhou. Tobacco causes head and neck cancers, but nasopharyngeal carcinoma is not included as causally related to smoking in the 2014 United States Surgeon General's report. Prospective evidence remains limited. We used Guangzhou Occupational Cohort data to conduct the first and robust prospective study on smoking and NPC mortality in an NPC high-risk region. METHODS: Information on demographic characteristics and smoking status was collected through occupational health examinations in factories and driver examination stations from March 1988 to December 1992. Vital status and causes of deaths were retrieved until the end of 1999. Cox proportional hazard model was used to assess the association of smoking with NPC mortality. RESULTS: Of 101,823 subjects included for the present analysis, 34 NPC deaths occurred during the average 7.3 years of follow up. The mean age (standard deviation) of the subjects was 41 (5.7) years. Compared with never smokers, the hazard ratio (HR) of NPC mortality was 2.95 (95% confidence interval 1.01-8.68; p=0.048) for daily smokers and 4.03 (1.29-12.58; p=0.016) for smokers with more than 10 pack-years of cumulative consumption, after adjusting for age, sex, education, drinking status, occupation and cohort status and accounting for smoking-drinking interaction. The risk of NPC mortality increased significantly with cigarettes per day (p for trend=0.01) and number of pack-years (p for trend=0.02). CONCLUSIONS: In this first and largest cohort in a high NPC risk region, smoking was associated with higher NPC mortality. The findings have shown statistically significant dose-response trend between smoking amount and smoking cumulative consumption and the risk of NPC mortality, but due to the small event number, further studies with larger sample size are needed to confirm the findings in the present study. Our results support that smoking is one of the risk factors likely to be causally associated with NPC mortality.