The underlying mechanism of transcription factor IRF1, PRDM1, and ZNF263 involved in the regulation of NPPB rs3753581 on pulse pressure hypertension.

To investigate the correlation between NPPB gene variants and pulse pressure hypertension and the underlying regulatory mechanisms and try to confirm that NPPB may be a potential molecular target of gene therapy for pulse pressure hypertension. A total of 898 participants were recruited from the First Affiliated Hospital of Fujian Medical University and the plasmids with differential expression of NPPB were constructed. Genotype distribution of NPPB(rs3753581, rs198388, and rs198389)was analyzed and the expression of N-terminal pro-B-type natriuretic peptide(NT-proBNP) and renin-angiotensin -aldosterone system(RAAS) related indicators were identified in the groups studied. According to a genotype analysis, there was a significant difference in the genotype distribution of NPPB rs3753581 among the groups (P = 0.034). In logistic regression analysis, NPPB rs3753581 TT was associated with a 1.8-fold greater risk of pulse pressure hypertension than NPPB rs3753581 GG (odds ratio = 1.801; 95% confidence interval: 1.070-3.032; P = 0.027). The expression of NT-proBNP and RAAS related indicators in clinical and laboratory samples showed striking differences. The activity of firefly and Renilla luciferase in pGL-3-NPPB-luc (-1299G) was higher than pGL-3-NPPBmut-luc(-1299 T)(P < 0.05). The binding of NPPB gene promoter rs3753581 (-1299G) with transcription factors IRF1, PRDM1, and ZNF263 was predicted and validated by the bioinformatics software TESS and chromatin immunoprecipitation(P < 0.05). NPPB rs3753581 was correlated with genetic susceptibility to pulse pressure hypertension and the transcription factors IRF1, PRDM1, and ZNF263 may be involved in the regulation of NPPB rs3753581 promoter (-1299G) on the expression of NT-proBNP/RAAS.

Flexible video endoscope versus Macintosh laryngoscope for orotracheal tracheal intubation in the lateral position: a study protocol for a randomized controlled trial.

BACKGROUND: Tracheal intubation with the patient in the lateral position is difficult because the laryngeal view is compromised during direct laryngoscopy. Flexible video endoscopes may facilitate intubation even when laryngeal views are poor on direct laryngoscopy because the patients are positioned laterally. Thus, this trial aims to compare the efficacy of flexible video endoscopes to Macintosh laryngoscopes for orotracheal intubation in the lateral position and to investigate their feasibility, i.e., whether the use of the two devices in combination can secure the airway when endotracheal intubation in the lateral position has failed using one device. METHODS: This will be a prospective, randomized, single-center, clinical trial. One hundred and seventy-four patients aged 18-65 years, who have been scheduled to undergo tracheal intubation under uniform general anesthetic techniques for elective kidney surgery in the lateral decubitus position will be randomly divided into the flexible video endoscope and the Macintosh laryngoscope groups. Primary outcomes include intubation time and intubation success rate. Secondary outcomes include overall user satisfaction (graded from 1 to 10 (1 = very poor, 10 = excellent)) and perioperative side effects and complications, such as frequency of esophageal intubation, lip or dental injury, sore throat, and hoarseness. DISCUSSION: The trial will clarify the efficacy of intubation with a Macintosh laryngoscope and a flexible video endoscope in the lateral position, and whether the two devices could be used in combination to secure the airway in cases where endotracheal intubation in the lateral position has failed with one device. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR- IOR-15007175 . Registered on 6 October 2015.

Gender-specific association between Apelin/APJ gene polymorphisms and hypertension risk in Southeast China.

To explore the role of genetic factors in the pathogenesis of hypertension, our study investigated the gender-specific association between four polymorphisms in the Apelin/APJ gene and hypertension risk in southeastern Chinese population. All participants including 645 hypertensive patients and 362 normotensive controls were genotyped for 4 gene polymorphisms associated with hypertension susceptibility including Apelin (rs909656, rs5975126) and APJ (rs10501367, rs11544374). According to genotype analysis, for male subjects, the frequencies of genotypes (P = 0.046 and 0.046, respectively) of rs10501367 and rs11544374 revealed significant differences between the hypertension and control groups. Moreover, for female subjects, there was significant difference on the genotype distribution of rs11544374 between two groups (P = 0.046). The association of rs10501367 with hypertension was significant for males under additive models and recessive models, even after adjusting for age, BMI, fasting glucose and waistline. Besides, significant association was observed for rs11544374 in females under additive models. As for haplotype analysis, haplotype T-A (in order of rs10501367 and rs11544374) in APJ gene was marginally overrepresented in controls (17.9%) compared to patients with hypertension (11.6%) in males (P = 0.003). The mutation of polymorphism rs10501367 in APJ gene decreased risk of hypertension in Chinese males.

Effect of goal-directed fluid therapy on early cognitive function in elderly patients with spinal stenosis: A Case-Control Study.

PURPOSE: To explore effect of goal-directed fluid therapy (GDFT) on early cognitive function in elderly patients with spinal stenosis. METHODS: 83 elderly patients with spinal stenosis were randomly classified into two groups: control group (n = 40) and GDFT group (n = 43). The Montreal Cognitive Assessment (MoCA) score, IL-6 and S100ß levels, hemodynamic parameters, cerebral oxygen saturation (rSO2), arterial lactic acid values, output of surgery, operation time and cases of hypotension, intraoperative complications within 7 days were recorded for all patients. RESULTS: The incidence of postoperative cognitive dysfunction (POCD) was about 21.67% in this study. The MoCA scores, inflammatory mediators, perfusion indexes (rSO2 and lactic acid)and intraoperative hemodynamics(HR, MAP, and CI)were not all the same at different time points (P < 0.05). The levels of inflammatory mediators (IL-6 and S100ß) in GDFT group were lower than those in the control group (P < 0.05). Total intake, amount of lactated Ringer's solution and cases of hypotension in GDFT group were significantly lower than control group (P < 0.05), but amount of voluven was higher than control group(P < 0.05). Compared with control group, the incidence of postoperative delirium, nausea and vomiting, and hypotension in GDFT group was lower (P < 0.05). CONCLUSIONS: GDFT can maintain the stability of perioperative hemodynamics in the prone position of elderly patients with spinal stenosis, improve the balance between perfusion of tissue and organ and supply and demand of oxygen, reduce the inflammatory response, and reduce the incidence of early POCD in this type of surgery.

Efficacy of an intercostal nerve block administered with general anesthesia in elderly patients undergoing distal gastrectomy.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of administration of an intercostal nerve block (INB) with general anesthesia to elderly patients undergoing a distal gastrectomy. METHODS: Elderly patients (>65 years) undergoing selective gastrectomy were randomly assigned to three groups (n = 80): general anesthesia (Group A); general + INB anesthesia (Group B); or, general + epidural anesthesia (Group C). General anesthesia was maintained with propofol, remifentanil and cisatracurium. The mean arterial blood pressure (MAP), heart rate (HR) and C-reactive protein (CRP) levels were determined before anesthesia (T0) and at 5 min after intubation (T1), skin incision (T2), exploration of the peritoneal cavity (T3), gastrointestinal anastomosis (T4), end of operation (T5) and 10 min after extubation (T6). RESULTS: MAP decreased at T1 in all groups (P < 0.05) and at T2, T4 and T5 in Group C (P < 0.05) and was lower in Group C than Group B at T2 and T4 (P < 0.05). There were no differences in MAP between Groups A and B or between Groups B and C. HR increased at T2-T6 in Group A (P < 0.05) and was higher at T2-T6 in Group B and Group C (P < 0.05). CRP levels decreased at T2-T5 in Groups B and C (P < 0.05) and were lower in Groups B and C compared with Group A (P < 0.05). Propofol and remifentanil doses were lower in Groups B and C (P < 0.05 and P < 0.01, respectively) and patients recovered faster than in Group A (P < 0.05). CONCLUSION: Administration of INB with general anesthesia enhanced analgesia, led to stable hemodynamics, and reduced anaesthetic consumption and postoperative stress response.

Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.

BACKGROUND: Mitochondrial injury is a major cause of sepsis-induced organ failure. Polydatin (PD), a natural polyphenol, demonstrates protective mitochondrial effects in neurons and arteriolar smooth muscle cells during severe shock. In this study, we investigated the effects of PD on renal tubular epithelial cell (RTEC) mitochondria in a rat model of sepsis-induced acute kidney injury. METHODS: Rats underwent cecal ligation and puncture (CLP) to mimic sepsis-induced acute kidney injury. Rats were randomly divided into sham, CLP + normal saline, CLP + vehicle, and CLP + PD groups. Normal saline, vehicle, and 30 mg/kg PD were administered at 6, 12, and 18 hours after CLP or sham surgery via the tail vein. Mitochondrial morphology, metabolism, and function in RTECs were then assessed. Serum cytokines, renal function, survival, and histologic changes in the kidney were also evaluated. RESULTS: CLP increased lipid peroxide content, lysosomal instability, and opening of the mitochondrial permeability transition pore and caused mitochondrial swelling. Moreover, mitochondrial membrane potential (ΔΨm) was decreased and ATP levels reduced after CLP. PD inhibited all the above effects. It also inhibited the inflammatory response, improved renal function, attenuated histologic indicators of kidney damage, and prolonged survival. CONCLUSIONS: PD protects RTECs against mitochondrial dysfunction and prolongs survival in a rat model of sepsis-induced acute kidney injury. These effects may partially result from reductions in interleukin-6 and oxidative stress.

Ulinastatin mediates protection against vascular hyperpermeability following hemorrhagic shock.

OBJECT: Recent studies have suggested that intrinsic apoptotic signaling cascade is involved in endothelial barrier dysfunction following hemorrhagic shock (HS), which results in vascular hyperpermeability. Our previous study demonstrated that ulinastatin (UTI) inhibits oxidant-induced endothelial hyperpermeability and apoptotic signaling. In present study, we hypothesized that UTI would improve HS-induced vascular hyperpermeability by regulating the intrinsic apoptotic signaling cascade. METHODS: Hemorrhagic shock was induced in rats by withdrawing blood to reduce the mean arterial pressure to 40-45 mmHg for 60 min, followed by reperfusion. Mesenteric postcapillary venules were examined for changes in hyperpermeability by intravital microscopy. In vitro, Rat lung microvascular endothelial cells (RLMVECs) were exposed in hemorrhagic shock serum for 120 min, followed by transendothelial electrical resistance (TER) estimation. Mitochondrial release of cytochrome c and caspase-3 activation was estimated in vivo. In vitro, ratio of cell apoptosis was evaluated by Annexin-V/PI double stain assay; mitochondrial membrane potential (∆Ψm) was determined with JC-1; intracellular ATP content was assayed by a commercial kit; reactive oxygen species (ROS) was measured by DCFH-DA; adherens junction protein ß-catenin was detected by immunofluorescense staining. RESULTS: In vivo, UTI attenuated HS-induced vascular hyperpermeability versus the HS group (P < 0.05); In vitro, UTI attenuated shock serum induced RLMEC monolayer hyperpermeability (P < 0.05). In vivo, UTI inhibited HS-induced cytochrome c release and caspase-3 activation (P < 0.05). In vitro, shock serum induced cell apoptosis, low ATP level, ∆Ψm depolarization, ROS increase were improved by UTI pre-treatment (P < 0.05). UTI improved shock serum induced disruption of endothelial cell adherens junction. CONCLUSIONS: UTI inhibits vascular hyperpermeability following HS. UTI regulates oxidative stress and intrinsic apoptotic signaling following HS.

Serum and urinary biomarkers for predicting acute kidney injury after partial nephrectomy.

PURPOSE: The purpose of this study was to evaluate the ability of specific biomarkers to predict acute kidney injury (AKI) after partial nephrectomy. METHODS: A prospective study of 89 patients undergoing partial nephrectomy was conducted in the First Affiliated Hospital of Fujian Medical University. The patients were divided into two groups according to AKI status: an AKI group and non-AKI group. Receiver operator characteristic (ROC) curves were generated and the areas under the curve (AUCs) were compared. RESULTS: Twenty-eight subjects (31.5%) developed AKI while sixty-one subjects (68.5%) did not. Vascular clamping time in the AKI group was longer than that in the non-AKI group (29 ± 17 min vs. 24 ± 9 min, P = 0.042). Eight patients (28.6%) received blood infusion in the AKI group compared with five patients (8.2%) in the non-AKI group (P = 0.021). The area under ROC curve for AKI prediction was 0.792 [95% confidence interval (CI) 0.697 to 0.888, P < 0.000] for serum cystatin C 24 hours after surgery and 0.756 (95% CI 0.656 to 0.857, P < 0.000) for serum cystatin C 48 hours after surgery. Multivariate regression analysis showed transfusion [Hazard ratio (HR) 3.712, P = 0.044] and 24 hours serum cystatin C (HR 41.594, P = 0.001) correlated with AKI. CONCLUSIONS: Postoperative serum cystatin C may be an early predictor for AKI after partial nephrectomy. Transfusion may be an independent risk factor for AKI after partial nephrectomy.

Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats.

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

The influence of goal-directed fluid therapy on the prognosis of elderly patients with hypertension and gastric cancer surgery.

PURPOSE: We aimed to investigate the influence of perioperative goal-directed fluid therapy (GDFT) on the prognosis of elderly patients with gastric cancer and hypertension. METHODS: Sixty elderly patients (>60 years old) with primary hypertension who received gastric cancer radical surgery and who were American Society of Anesthesiologists (ASA) class II or III were enrolled in the current study. Selected patients were divided randomly into two arms, comprising a conventional intraoperative fluid management arm (arm C, n=30) and a GDFT arm (arm G, n=30). Patients in arm C were infused with crystalloids or colloids according to the methods of Miller's Anesthesia (6th edition), while those in arm G were infused with 200 mL hydroxyethyl starch over 15 minutes under the FloTrac/Vigileo monitoring system, with stroke volume variation between 8% and 13%. Hemodynamics and tissue perfusion laboratory indicators in patients were recorded continuously from 30 minutes before the operation to 24 hours after the operation. RESULTS: Compared with arm C, the average intraoperative intravenous infusion quantity in arm G was significantly reduced (2,732±488 mL versus 3,135±346 mL, P<0.05), whereas average colloid fluid volume was significantly increased (1,235±360 mL versus 760±280 mL, P<0.05). In addition, there were more patients exhibiting intraoperatively and postoperatively stable hemodynamics and less patients with low blood pressure in arm G. Postoperative complications were less frequent, and the time of postoperative hospital stay shorter, in arm G. No significant differences were observed in mortality between the two arms. CONCLUSION: Our research showed that GDFT stabilized perioperative hemodynamics and reduced the occurrence of postoperative complications in elderly patients who underwent gastric cancer surgery.

Cardioprotective effects of phosphocreatine on myocardial cell ultrastructure and calcium-sensing receptor expression in the acute period following high level spinal cord injury.

Phosphocreatine (PCr) mobilizes high-energy phosphates in cardiac muscles, which is potentially useful as a cardioprotective agent in patients with spinal cord injury (SCI). The cardioprotective effects of PCr on myocardial cell ultrastructure and calcium-sensing receptor (CaSR) expression following high-level spinal cord injury (SCI) were investigated. Healthy adult male Sprague-Dawley (SD) rats (n=54) weighing 250-300 g were subjected to C7 SCI injury by Allen's method with or without treatment by abdominal injection of PCr (200 mg/kg) at 6, 12, 24 or 48 h (SCI + treatment and SCI-only groups, respectively; 6 rats/group/time point). Right apical tissues were sampled 2 h following each time interval. Surgeries without SCI were performed in 6 control rats (sham operation group). Cardiac troponin I (cTnI), serum creatine kinase (CK) and creatine kinase (CK-MB) levels were assessed automatically. Myocardial morphology was examined by transmission electron microscopy (TEM). Quantitative real­time polymerase chain reaction (qRT-PCR) and western blot analysis were used to determine myocardial tissue calcium-sensing receptor (CaSR) mRNA and protein expression, respectively. Normal myocardial ultrastructure was observed in the sham operation group, while SCI-only groups exhibited progressive and extensive damage to myofibrils, sarcomere structure, mitochondrial membranes and vacuole structures, occasionally accompanied by punctured cell membranes, nuclear chromatin condensation and cavitation. SCI + treatment groups, however, exhibited significantly relieved ultrastructural abnormalities and reduced the levels of CaSR, cTnI, CK and CK-MB mRNA and protein expression at all time intervals (P<0.05). In the SCI rat model, PCr exhibited cardioprotection by relieving myocardial ultrastructural abnormalities and preserving the normal metabolic energy balance, including calcium regulation.

Effect of adenoviral delivery of prodynorphin gene on experimental inflammatory pain induced by formalin in rats.

Circumstantial evidences suggest that dynorphins and their common precursor prodynorphin (PDYN) are involved in antinociception and neuroendocrine signaling. DREAM knockout mice had increased levels of PDYN and dynorphin expression, and reduced sensitivity to painful stimuli. However, some data support the notion that the up-regulation of spinal dynorphin expression is a common critical feature in neuropathic pain. It is not clear whether the production of dynorphin A can be increased when more PDYN is present. In this study we investigated the changes in pain behaviors, spinal PDYN mRNA expression and dynorphin A production on formalin-induced pain in rats receiving the pretreatment of adenoviral delivery of PDYN. Our results showed that the adenoviral transfer of PDYN gene was sufficient to reduce pain behaviors resulting from formalin injection, and the antinociceptive effect after receiving the pretreatment of adenoviral delivery of PDYN was mediated at the level of the spinal cord via KOR.

Therapeutic effect of emodin on collagen-induced arthritis in mice.

Emodin, an anthraquinone isolated from the Chinese herb Radix et Rhizoma Rhei, has been reported to have anti-inflammatory, antibacterial, and antitumor activities. However, the effect of emodin on collagen-induced arthritis (CIA) has not yet been investigated. The purpose of this study was to investigate whether emodin has a protective effect against collagen-induced arthritis in mice and its possible mechanisms. CIA was induced in mice by immunization with bovine type II collagen. The mice were treated with emodin (5, 10, and 20 mg/kg/day, i.g.) from days 21 to 42 after immunization. The clinical scores and hind paw swelling were evaluated. The expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) in synovial tissues was determined. The levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in the plasma were measured by enzyme-linked immunosorbent assay. The results showed that emodin treatment significantly alleviated the severity of the disease, based on the reduced hind paw swelling and clinical scores, compared with untreated CIA mice. Comparing with untreated CIA mice, emodin treatment inhibited the levels of TNF-α and IL-6 in the plasma, PGE2 production, and COX-2 protein expression in synovial tissues in a dose manner. In conclusion, our results suggest that anti-inflammatory effects of emodin against collagen-induced arthritis in mice may be due to its ability to inhibit pro-inflammatory mediators. Emodin may be a promising potential therapeutic reagent for arthritis treatment.

Relationship between EEG beta power abnormality and early diagnosis of cognitive impairment post cerebral hemorrhage.

Cerebral hemorrhage is a common disease of older adults, which could increase the risk of cognitive impairment. Electroencephalogram (EEG) characteristics can be analyzed to investigate the applied value in the assessment of cognitive impairment of the patients with cerebral hemorrhage. One hundred eighty-two patients (including patients with cognitive impairment [CHCI] and patients with cognitive normality [CHNC] with cerebral hemorrhage, and 120 normal healthy persons [control; CN]) were recruited between July 2008 to March 2012 at the department of neurology. All patients were analyzed by EEG, and analysis results were compared to the Montreal Cognitive Assessment (MoCA) scale, using the methods of correlation analysis, clustering analysis, and concordance analysis. The results indicated that patients with CHCI had significantly lower EEG beta power (0.814 ± 0.113 mcV(2)) relative to CHNC (1.601 ± 0.186 mcV(2), P < .01) or CN group (1.713 ± 0.201 mcV(2), P < .01). Significant negative correlation was found between the beta power and hemorrhage region, age, hemorrhage size, hemorrhage amount (r 1 = -.92223, r 2 = -.81084, r 3 = -.79258, r 4 = -.84961, respectively, all P < .001). There was good concordance between K-means clustering algorithm calculating the beta power and MoCA scoring (Kappa = 0.899, P < .001). In conclusion, the preliminary findings suggest that the recognition techniques of EEG hold considerable promise for the assessment of cognitive impairment post cerebral hemorrhage, which negatively related to the hemorrhage region, hemorrhage size, hemorrhage amount, and age.

Construction of a bicistronic recombinant adenoviral vector for human interleukin-10 and enhanced green fluorescent protein expression in bone marrow mesenchymal stem cells.

BACKGROUND: Human interleukin-10 (hIL-10) is a cytokine synthesis inhibitory factor, which is involved in various immune responses. The purpose of this study was to construct an adenoviral vector carrying the hIL-10 gene for expression of biologically active hIL-10 in rat bone marrow mesenchymal stem cells (rMSCs). METHODS: A pSNAV2.0-hIL10 plasmid was used as a template to obtain a hIL-10 cDNA fragment that was subcloned by restriction enzyme digestion and ligation into a pDC316-IRES-EGFP-lacZ alpha plasmid carrying an enhanced green fluorescent protein (EGFP) marker gene. The pDC316-hIL-10-IRES-EGFP plasmid was linearized by PmeI digestion and used to transfect HEK293 packaging cells using the adenovirus packaging system AdMax. Virus particles were amplified by repeatedly infecting HEK293 cells with the seed virus and then purified by ion exchange. After the number of virus particles and titer was determined, rMSCs were infected with the adenoviral vector. The infection rate was determined by fluorescence microscopy and flow cytometry, and hIL-10 protein expression in rMSCs was measured by Western blotting. RESULTS: The virus particle concentration, OD260/280 value and virus titer of the amplified and purified recombinant adenovirus were 3.2 × 10(11) VP/ml, approximately 2.0, and 1.1 × 10(10) TCID50/ml, respectively. Bright green fluorescence was observed by fluorescence microscopy and flow cytometry in the recombinant adenovirus-infected rMSCs. GFP expression was considered the multiplicity of infection (MOI) and was time-dependent. The infection rate was 92.9% at 100 MOI. CONCLUSIONS: A bicistronic recombinant adenoviral vector for hIL-10 and EGFP gene expression were successfully constructed. The infection rate of rMSCs by the adenovirus was high (92.9% at 100 MOI) and the target gene hIL-10 was highly expressed in cells. The present study provides an experimental basis for further research of immunosuppressive therapy using hIL-10. The expression level of hIL-10 protein as detected by Western blotting was also MOI- and time-dependent.

PRSS1 intron mutations in patients with pancreatic cancer and chronic pancreatitis.

Genetic risk factors of chronic pancreatitis (CP) have been identified and a number of studies have found that CP can lead to pancreatic cancer. Therefore, the detection of pancreatitis-associated gene mutations can aid the pancreatic cancer diagnostic process. Mutations in three genes, the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the pancreatic secretory trypsin inhibitor (SPINK1) gene, have been identified as risk factors for CP. The aim of this study was to describe specific novel mutations in the intron of the PRSS1 gene in patients with pancreatic cancer and CP. A total of 65 unrelated patients with pancreatic cancer and 29 with CP were reviewed. Mutations and polymorphisms of the PRSS1 gene were analyzed by direct sequencing. Information regarding clinical data and smoking exposure was collected by personal interviews using a structured questionnaire. IVS 3+36 A>G mutation in the PRSS1 gene was found in 2 cases with pancreatic cancer, and these 2 patients were classified as never-smokers. IVS 3+127 T>A and IVS 3+157 G>C double mutations were identified in one patient with CP. All patients were found to have serum trypsin levels lower than that of the normal controls. Therefore, the PRSS1 gene mutation may be a special common cause of pancreatic cancer and CP.