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It has been shown that prostaglandin (PG) E 2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE 2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE 2 in male rats. The core temperature (T core ) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE 2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE 2 . We demonstrated that EP3 receptor was a pivotal receptor for PGE 2 -induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE 2 , respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE 2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE 2 ; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (I A ) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE 2 ; however, the I A current density was significantly increased by PGE 2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE 2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE 2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of I A currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Competing Interests: The authors declare no conflicts of interest.

Background: Restoration with locking-taper implants is a widely used methodology. However, conical connection systems such as locking-taper implant systems have rarely been examined. This study provides a retrospective investigation of locking-taper fixed restorations, mainly focusing on prosthetic complications., Methods: Patients undergo treatment with conical connected implants from 2008 to 2010 were examined. Preparation of the implant sites was performed according to the standard procedures for the Bicon system. Bone healing took over 6 months, and the prosthetic procedure was initiated thereafter. Integrated abutment crowns or gold porcelain crowns were used, and the prosthesis type was a single crown or a fixed dental prosthesis. Once the crown was in place, its occlusion was thoroughly checked and adjusted, and then the crown was glazed or finely polished. The Kaplan-Meier method was used to calculate the cumulative complication-free rates for 5 and 10 years. Additionally, a Cox regression model was used to identify the factors that independently influenced the results. Implant survival and marginal bone loss were also investigated., Results: A total of 392 patients who underwent 541 implants and 434 locking taper implant-based restorations from 2008 to 2010 were examined. The overall 5-year cumulative complication-free rate was 83.34%. The most common prosthetic complication was veneer chipping, with a frequency of 67.53%. According to the Cox regression model, the complication-free rate of integrated abutment crowns was significantly higher than that of gold porcelain crowns, that of molar regions was significantly higher than that of premolar regions, and that of females was significantly higher than that of males. Only three implant failures happened, and the mean marginal bone loss values at 1- year, 5-years and 10- years were 0.25 mm (95% CI ± 0.12), 0.40 mm (95% CI ± 0.03) and 0.51 mm (95% CI ± 0.05), respectively., Conclusion: Veneer chipping was the most common complication with locking-taper implant-supported fixed restorations. The incidence of complications for IACs is significantly higher than that for GPCs. Age, location, and prosthesis type are not determinants of prosthetic complications. Besides, the long-term clinical effect of locking-taper implant can meet the clinical needs. The bone tissue level around the implant can maintain long-term stability., (© 2021. The Author(s).)

Purpose: To evaluate the wear of zirconia on natural teeth in humans in vitro and in vivo., Materials and Methods: Embase, the Cochrane Database, PubMed, and the Web of Science were searched (January 2014 to May 2019), and all references were retrieved. After preliminary screening of the literature, two researchers read the full texts of the remaining literature and determined whether the literature should be included. Data and information were extracted from the included literature, then analyzed and discussed., Results: A total of 49 in vivo experiments and 229 in vitro experiments were retrieved. After duplication removal and screening, 7 in vivo studies and 13 in vitro studies were included. The results of the in vitro studies showed that fine polished zirconia causes less antagonist wear on natural teeth than other treatments with zirconia or other restorative materials. The results of the in vivo studies showed the antagonist wear of zirconia on natural teeth was within the clinically acceptable range., Conclusion: Both in vivo and in vitro studies have shown polishing can reduce the wear of zirconia on natural teeth more than glazed or veneering porcelain. However, whether glazed zirconia causes less natural tooth wear after polishing is still a matter of debate. Due to the short observation period and heterogeneity of the experiment, the above conclusions should be carefully interpreted.

Acrylamide has been shown to be neurotoxic. Brain-derived neurotrophic factor (BDNF) can alleviate acrylamide-induced synaptic injury; however, the underlying mechanism remains unclear. In this study, dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma (NB-1) cells were exposed with 0-100 μg/mL acrylamide for 24-72 hours. Acrylamide decreased cell viability and destroyed synapses. Exposure of co-cultured NB-1 cells and Schwann cells to 0-100 μg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF, suggesting that Schwann cells can activate self-protection of neurons. Under co-culture conditions, activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect. Exogenous BDNF can increase expression of TrkB, Erk1/2, and synapsin I, while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes. Taken together, Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway, indicating that BDNF plays an important role in this process. Therefore, exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury. This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control, a division of the Chinese Center for Disease Control and Prevention (approval No. EAWE-2017-008) on May 29, 2017., Competing Interests: None

Abstract: With the rapid development of the social economy in China, the incidence of diseases caused by excessive drinking is gradually increasing as well. Alcoholic cardiomyopathy refers to long-term high intake of ethanol, and has typical dilated cardiomyopathy characteristics, such as, hemodynamic changes, symptoms, signs, and morphological features. It is a kind of cardiomyopathy that excludes other causes of dilated cardiomyopathy. Due to the lack of specific pathological changes, the forensic pathological identification of alcoholic cardiomyopathy can only be based on the patient's medical history and by ruling out other causes of cardiomyopathy. This paper reviews the pathogenesis and forensic identification of alcoholic cardiomyopathy in order to provide reference for forensic pathologists and clinicians., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

BACKGROUND Blood transfusion is common during liver resection (LR). The objective of the present study was to investigate the effects of intraoperative transfusion of different blood components on post-LR morbidity. MATERIAL AND METHODS We included 610 patients undergoing LR and grouped them according to intraoperative transfusion of different blood components: packed red blood cells only (PRBC, n=81); frozen fresh plasma, platelets, and cryoprecipitate (FPC, n=38); transfusion only with PRBC + FPC transfusion (n=244); and no blood transfusion (n=247). Propensity score matching (PSM) analysis was used to mitigate selection bias in comparisons. RESULTS The overall blood transfusion rate was 59.5%. In comparison with the no blood transfusion group, PRBC-only and PRBC + FPC transfusion were more common in patients with lower preoperative hemoglobin, worse liver function, larger tumor size, and undergoing a major LR, and thus were associated with increased postoperative morbidity. In contrast, FPC-only transfusion was more frequent in patients with a liver function of Child-Pugh B and lower preoperative albumin vs. the no blood transfusion group. In the propensity model, transfusion of PRBC (PRBC-only and PRBC+FPC) and FPC (FPC-only and FPC+PRBC) were significantly associated with increased postoperative complications vs. the no blood transfusion group (OR and 95% CI, 1.9 [1.2-2.7], p=0.002; OR and 95% CI, 1.6 [1.0-2.4], p=0.029). In contrast, intraoperative PRBC-only or FPC-only transfusion showed no significant adverse effects on postoperative morbidity. CONCLUSIONS Allogenic transfusion of PRBC and FPC blood components was associated with increased postoperative morbidity after liver surgery. Different blood components should be used only when absolutely necessary.

Commotio cordis （CC） is the acute death caused by the cardiac rhythm disorder after a sudden blunt external force to the precordium of a healthy person without previous heart disease. As one type of violent heart damage, CC is rare with relatively small external force and sudden death, therefore causing disputes. This paper reviews the epidemiology, mechanisms and the key points in forensic identification of CC, discusses the identification and antidiastole of CC, myocardial contusion, sudden cardiac death and death from inhibition, and provides assistance to forensic pathologists to identify such causes of death., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Objective: The main purpose of this study was to ascertain whether (or not) exposure to benzene, toluene, xylene and ethylbenzene (BTXE) , under normal working conditions, was associated with any health effects. Methods: From January to December 2014, the workplaces concentrations of BTXE were measured of 71 enterprises in Suzhou Industrial Park. Occupational health examination were investigated on 764 employees who exposed to BTXE, as well as 4409 employees of the corresponding enterprises who unexposed to BTXE, and analyzed the data of the two groups. Results: A total of 6 monitoring sites in 3 enterprises BTXE concentrations excess of the standards, the unexposed group was under the limit of detection. The means of red blood cell count, hemoglobin, hematocrit, intermediate cell count and percentage of intermediate cells were significantly higher in exposed group than in unexposed group ( P <0.05) . Conversely, platelet count was significantly lower in exposed group than in unexposed group ( P <0.05) . The proportion of red blood cell volume, lymphocyte count and percentage of intermediate cells were significantly lower in exposed group than in unexposed group ( P <0.05) . Both means and proportion of glutamic pyruvic transaminase and urea nitrogen were significantly higher in exposed group than in unexposed group ( P <0.05) . The positive rate of protein, urine, urine red blood cell were significantly higher in exposed group than in unexposed group ( P <0.05) . The abnormal rate of electrocardiogram, liver and kidney B scan were significantly higher in exposed group than in unexposed group ( P <0.05) . Multivariate logistic regression analysis revealed that percentage of intermediate cells increased, urea nitrogen increased, urine protein positived, urine red blood cells positived in exposed group the OR values were 1.689, 3.291, 3.163 and 1.743 ( P <0.05) . Conclusion: Occupational exposure to low concentrations of BTXE had a certain impact on the blood system and liver and kidney function of the employees, occupational health surveillance for such people should be strengthened.

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV 1 ), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV 1 / FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF 50% ), and forced expiratory flow at 75% of FVC (FEF 75% ) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF 75% were associated with the increasing levels of PAHs meta-bolites (p<0.05), and there were negative correlations between FEV 1 , FEV 1 /FVC, MMF, FEF 50% , and FEF 75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index.

Objectives: To assess the safety and tolerance of healthy volunteers to as tragalosides injection (AGI), and to determine a safe dose range for phase II clinical trial., Methods: A total of 62 healthy volunteers participated in this study, with 26 being given a single AGI of 100 mL, 200 mL, 300 mL, 400 mL, 500 mL, or 600 mL and 36 subjects being given 500 mL, 400 mL, 200 mL or 300 mL of AGI once a day for 7 d. Discomfortsymptoms, vital signs and safety problems were recorded 3 d and 7 d after the administration of AGI. The results were analyzed., Results: Of the 62 participants, 40 adverse events (AEs) were reported by 31 participants, which included 23 mild adverse reactions (ADRs) and 4 moderate ADRs. Nine AEs were reported by 9 participants with single AGI, including 7 ADRs. Fourteen AEs were reported by 10 participants with 500 mL and 400 mL multiple AGI, including 12 ADRs occurred in 9 participants.Seventeen AEs were reported by 12 participants with 300 mL and 300 mL multiple AGI, including 3 mild ADRs. The main ADRs included abnormal liver function [slightly elevated glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST),and serum total bilirubin (TBil)], low blood potassium, increased urine red blood cell count, rash, and phlebitis., Conclusions: The maximum tolerance is 600 mL for single-dose treatment, and 400 mL for multiple-dose (7 d). The dose guidance given in this study should be examined its effects and safety in patients with coronary heart disease in phase II clinical trial.

We report the first example of the highly enantioselective synthesis of structurally diverse chiral dithioketals via asymmetric sulfenylation of various types of S-based nucleophiles, catalyzed by a cheap cinchona alkaloid derivative, dihydroquinine.

Background: The nanotechnology boom and the ability to manufacture novel nanomaterials have led to increased production and use of engineered nanoparticles (ENPs). However, the increased use of various ENPs inevitably results in their release in or the contamination of the environment, which poses significant threats to human health. In recent years, extraordinary economic and societal benefits of nanoproducts as well as their potential risks have been observed and widely debated. To estimate whether ENPs are safe from the onset of their manufacturing to their disposal, evaluation of the toxicological effects of ENPs on human exposure, especially on more sensitive and vulnerable sectors of the population (infants and children) is essential., Data Sources: Papers were obtained from PubMed, Web of Science, and Google Scholar. Literature search words included: "nanoparticles", "infants", "children", "exposure", "toxicity", and all relevant cross-references., Results: A brief overview was conducted to 1) characterize potential exposure routes of ENPs for infants and children; 2) describe the vulnerability and particular needs of infants and children about ENPs exposure; 3) investigate the current knowledge about the potential health hazards of ENPs; and 4) provide suggestions for future research and regulations in ENP applications., Conclusions: As the manufacturing and use of ENPs become more widespread, directed and focused studies are necessary to measure actual exposure levels and to determine adverse health consequences in infants and children.

A chiral secondary amine phosphoramide was developed and identified as a powerful catalyst for the Mukaiyama-Michael addition of fluorinated enol silyl ethers to tetrasubstituted olefins. The resulting products are obtained with high enantioselectivities and contain a quaternary carbon stereocenter bearing either a difluoroalkyl or monofluoroalkyl group., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ojective: To explore the changes of serum IgE and tryptase caused by anaphylactic shock rats and discuss the relation to PMI and preservative environment of corpse and specimen., Methods: Rats were used for establishing anaphylactic shock models and randomly divided into room temperature group, refrigeration group, frozen group, manual hemolysis group, specimen preservation group. And the control group was also established. The blood samples were collected after rats were sacrificed. The degree of hemolysis was graded according to the color of the upper layer of the serum. The mass concentration of IgE and tryptase in each group was detected by ELISA., Results: The levels of serum IgE and tryptase in anaphylactic shock dead rats were higher than that of the control group. Room temperature and frozen made obviously differences on the levels of serum IgE and tryptase with various PMI. The levels of serum IgE and tryptase in refrigeration group showed relatively stable. The levels of serum tryptase and IgE were elevated with differently increasing hemolysis. The levels of serum IgE and tryptase showed no obvious changes during the specimen kept under different temperature conditions for 25 days., Conclusion: Serum IgE and tryptase obviously increased in anaphylactic shock rats. However, the levels were influenced by PMI and environmental temperature, especially under the conditions of room temperature and frozen.

In this paper, first time as our knowledge, we describe the development and performance evaluation of a 4.4 μm external cavity quantum cascade laser based laser heterodyne radiometer. Laser heterodyne spectroscopy is a high sensitive laser spectroscopy technique which offers the potential to develop a compact ground or satellite based radiometer for Earth observation and astronomy. An external cavity quantum cascade laser operating at 4. 4 μm, with output power up to 180 mW and narrow line width was used as a local oscillation. The external cavity quantum cascade laser offers wide spectral tuning range, it is tunable from 4.38 to 4.52 μm with model hop free and can be used for simultaneous detections of CO2, CO and N2 O. A blackbody was used as a signal radiation source. Development and fundamental theory of Laser heterodyne spectroscopy was described. The performance of the developed Laser heterodyne radiometer was evaluated by measuring of CO2 spectral at different pressures. Analyses results showed that a signal-to-noise ratio of 86 was achieved which was less than the theoretical value of 287. The spectral resolution of the developed Laser heterodyne spectroscopy is about 0.007 8 cm(-1) which could meet the requirement of high resolution spectroscopy measurement in the case of Doppler linewidth. The experiment showed that middle Infrared laser heterodyne spectroscopy system had high signal-to-noise ratio and spectral resolution, and had broad application prospect in high precision measurement of atmospheric greenhouse gas concentration and vertical profile.

Based on the investigation of phytoplankton and water body nutrient concentration in the ecology-monitoring area of Changli in summer from 2005 to 2013, the phytoplankton community structure was analyzed. The result showed that in recent 9 years, 3 phyla including 23 families, 39 genera and 105 species of phytoplankton were identified, in which 85.7% were diatoms and 13.3% were dinoflagellate. Only one species was found belonging to golden algae. There was great difference in dominant species among different years. According to the value of dominance, there were Coscinodiscus radiatus, Coscinodiscus debilis, Rhizosolenia styliformis, Cerataulina bergoni, Coscinodiscus wailesii, Thalassiosira sp., Ceratium tripos, Chaetoceros lorenzianus, Skeletonema costatum. The cell abundance was decreased yearly. The Shannon-Wiener index of phytoplankton community ranged from 0.015 to 3.889, and the evenness index ranged from 0.009 to 1, which showed little yearly change. And phytoplankton species were unevenly distributed among the 19 sites, there were relatively low amount of dominant species, but the dominance was relatively high. Canonical Correspondence Analysis (CCA) results of the phytoplankton community and its environmental factors showed that the environmental factors influencing the change of phytoplankton community structure in summer included water temperature, nutrients (TP, TN and NO3(-) -N, NH4(+)-N) and salinity, and the structural change was the result of the interactions of different environmental factors.

A new cinchona alkaloid derived bifunctional tertiary amine-phosphoramide is identified as a highly enantioselective catalyst for Michael addition of both unprotected 3-arylthio- and 3-alkylthiooxindoles to nitroolefins. The phosphoramide moiety of plays an indispensable role in this reaction.

Objective: To determine the effects of Ginkgo biloba extract (EGB) on major periodontal pathogens in subgingival plaque., Methods: Sixty patients with moderate to severe periodontitis were selected and randomly assigned to 3 groups: EGB group, a positive (periocline) and a negative control groups. Subgingival plaque samples were collected before treatment and 1 week, 2 months and 4 months after treatment. The detection rates of 4 major periodontal pathogens-Treponema denticola (Td), Tannerella forsythus (Tf), Prevotella intermedia (Pi), and Porphyromonas gingivalis (Pg)-were detected by polymerase chain reaction (PCR). Clinical indicators were examined before treatment, 3 and 6 months after treatment., Results: EGB significantly decreased the detection rate of all the 4 pathogens 1 week after treatment, and then gradually increased at 2 and 4 months. EGB's inhibition effect was better than or comparable to periocline, except for Pg in short-term. The difference of plaque index (PLI) and bleeding index (BI) was not statistically significant among the groups, while for probing depth (PD) and attachment loss (AL), the difference was statistically significant between the EGB group and negative control group at 3 and 6 months after treatment., Conclusion: EGB significantly inhibited major periodontal pathogens and can be used as an adjuvant for periodontitis treatment.

Statement of Problem: Dental alloys have different mechanical properties compared with enamel. However, few studies have been conducted to determine the effects of the retention forces of clasps when applied on different cast crowns., Purpose: The purpose of this study was to evaluate the retention forces of cast circumferential clasps made of cobalt-chromium alloy on complete cast crowns made of cobalt-chromium (CC group) and gold-silver-palladium (AC group) alloys, and to observe their abrasion patterns., Material and Methods: Two groups of specimens were fabricated (n=5) and subjected to repeated insertion-removal tests (100 to 15,000 cycles). The mean values of removal forces at 100, 400, 800, 1500, 4500, 7500, 10,000, and 15,000 cycles, and their corresponding change rates compared with the initial 100 cycles' retention were determined. The differences between the 2 groups were analyzed by 2-way repeated measures analysis of variance at 100, 7500, and 15,000 cycles. The surfaces of specimens were observed with scanning electron microscopy., Results: There were significant differences between the CC and AC groups in retention forces (P<.05). Clasp retention showed a descending trend for cobalt-chromium alloy crowns from the initial value, which decreased by 29.9% after 15,000 insertion-removal cycles. A sharp increase in retention could be observed in the AC group, which rose by 99.7% ultimately. The worn surfaces of the gold-silver-palladium crowns showed different wear patterns compared with the cobalt-chromium alloy crowns., Conclusions: The results indicate that cobalt-chromium alloy crowns and gold-silver-palladium alloy crowns perform differently when cobalt-chromium alloy clasps are designed as retainers for partial removable dental prostheses. Crown designs should be changed, depending on the retainer and clasp materials for partial removable dental prostheses abutment teeth., (Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The People's Hospital of Shimian County is located in the underdeveloped agricultural county of western China with a population of 120,000. In light of the region's geographic location and cultural characteristics, the hospital has laid out a development strategy of becoming a regional healthcare service center-in Shimian and extends services to surrounding regions. Its reform process would start with the overhaul of the personnel system to rejuvenate the hospital's internal operation, and then move towards more comprehensive reforms on corporate governance structure and trans-regional integration of medical resources. On the basis of constructing a digital hospital, we would build an information platform to explore the 'Shimian model' of information-based healthcare reform through regional medical coordination and whole-sector oversight. An appropriate strategy and development roadmap, comprehensively internal and external reforms and persistent culture building, as well as the use of information technology will help put the hospital onto a track of fast and healthy development and in the right direction of healthcare reform that accords with our national circumstances. This article makes a review, summary and analysis of the process and further discusses about how to overhaul the healthcare system through reform and development.

Fatal anaphylactic shock is common in forensic practice. However, it is difficult to diagnose for lacking specific pathological and morphologic changes in forensic autopsy. The application of some biochemical indicators is of great significance. This paper reviews the biological characteristics of some biochemical indicators and detection methods. The forensic application, problems and prospects of these indicators are also introduced in details. The stable biochemical indicators, IgE, tryptase and chymase, show great potential and advantages in the identification of fatal anaphylactic shock in forensic medicine.

Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRT- PCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR- 196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

We report a highly enantioselective Cu(I)-catalyzed azide-alkyne cycloaddition via asymmetric desymmetrization of oxindole-based 1,6-heptadiynes, which furnishes quaternary oxindoles bearing a 1,2,3-triazole-containing moiety with 84-98% ee.

Objective: To investigate the expression of brain natriuretic peptide (BNP) in rat myocardial tissue after acute cardiac dysfunction and to explore the role of BNP in diagnosis of cardiac dysfunction in forensic practice., Methods: Rat models of acute cardiac dysfunction were established. The expression of BNP protein and BNP mRNA in myocardial tissue after cardiac dysfunction were detected by immunohistochemistry, Western blotting and real-time RT-PCR., Results: The extent of positive staining of BNP increased over the time course during cardiac dysfunction. The expression of BNP showed mild positive in cardiomyocytes from 1 h to 2 h. From 4 h to 6 h, the expression was moderate positive. From 10 h to 12 h, the BNP showed a strongest positive expression. The expression of BNP presented a significant raise with the increasing time of cardiac dysfunction by Western blotting and real-time RT-PCR. The expression of BNP mRNA increased significantly 1 h after cardiac dysfunction., Conclusion: Investigating the expression of BNP protein and BNP mRNA in myocardial tissue may provide a new approach to evaluate the cardiac function for forensic pathologists.

Objective: To investigate the repeatability of three-dimensional (3-D) cephalometric measurements for the clinical application of 3-D cephalometry., Methods: Forty-nine measurements that widely used in traditional cephalometric analyses were defined in 3-D cone-beam CT (CBCT) images. Three examiners identified landmarks on CBCT images of 17 subjects with normal occlusion, respectively, and 3-D measurements were exported automatically by software SimPlant. Inter-examiner reliability correlation coefficients (ICC) were obtained for all measurements., Results: Repeatability of 36 measurements was high (ICC value greater than 0.9), including SNA, SNB. Repeatability of 11 measurements was moderate (ICC value between 0.8 and 0.9), including CoL-GoL, CoL-MSP. Repeatability of 2 measurements was low (ICC value lower than 0.8), including Gn-MSP and MPR-MSP., Conclusions: Most 3-D cephalometric measurements based on CBCT had high repeatability. However, some 3-D cephalometric measurements had limited repeatability.

Objective: To analyze craniofacial growth three-dimensionally for adolescents with normal occlusion in Beijing., Methods: One hundred and twenty-six adolescents with normal occlusion were selected according to the criteria. The sample was divided into four age groups (53 within 4 years, 30 within 7 years, 27 within 10 years and 16 within 13 years). Information of growth was collected. Three-dimensional cephalometric system based on cone-bean CT was established., Results: From 4 to 13 years Co-A increased (14.55 ± 1.15) mm on average on the left and (13.66 ± 1.14) mm on the right, and Co-Gn increased (22.89 ± 1.40) mm on the left and (22.82 ± 1.38) mm on the right; and U1-NA increased (2.20 ± 0.44) mm on the left and (1.60 ± 0.46) mm on the right; and CoL-CoR and GoL-GoR increased (13.31 ± 1.21) mm and (18.59 ± 1.40) mm, and N-Me increased (18.03 ± 1.32) mm.SN-PP and SN-MPL basically remained unchanged., Conclusions: Adolescents with normal occlusion in Beijing grew obviously in three-dimensions and developed harmoniously.

Objective: To investigate the effect of the continuous light force to the donor teeth on the periodontal healing after transplantation., Methods: Thirty-two maxillary and mandibular incisors in four 10-month-old male Beagle dogs were autotransplanted. The pulps were removed in all teeth. The teeth were divided into four groups, one control and three experimental groups. In control group (group 1), the teeth were unloaded. In the other three experimental groups, continuous force (0.49 N) was applied in the 1st (group 2), 2nd (group 3) and 4th (group 4) week, respectively. The dogs were sacrificed in the 8th week. The tissue blocks were demineralized and sectioned perpendicular to the long axis of the teeth. The histological analysis was made., Results: Histomophometric analysis revealed a significantly lower occurrence of replacement root resorption in the group 3 (2.1%) than in the control group (12.5%, P < 0.05). The significant lower incidence of replacement root resorption, and a higher surface and inflammatory root resorption were found in group 2 (6.3% and 68.8%) than in the control group (12.5% and 41.7%, P < 0.05). No significant difference was found between group 4 and control group (P > 0.05)., Conclusions: The orthodontic force promoted the regeneration of the periodontal ligament and prevented dentoalveolar ankylosis, whereas excessive initial force might cause root and bone resorption.

Objective: To observe the changes of hypoxia-inducible factor-1 alpha (HIF-1alpha), the expression in the early stage (within 6 h) of acute myocardial ischemia and to explore the potential forensic application., Methods: SD rats were randomly divided into one control group, one sham operation group and five myocardial ischemia groups which received ligation of the left anterior descending (LAD) coronary artery. The five experiment groups divided into 15min, 30min, 1 h, 3 h and 6h after LAD ligation. The expression of HIF-1alpha was detected by immunohistochemistry, immunofluorescence and Western blotting, respectively., Results: Both the control group and sham operation group showed no expression of HIF-1alpha, whereas the expression of HIF-1alpha could be weakly detected beneath the endocardium at 15 min after LAD ligation. With the increase of myocardial ischemia process, the positive staining gradually extended from endocardium to epicardium, reached the peak at 3 h, and began to decrease gradually at 6h after LAD ligation but still maintained at a relatively high level. In addition, the expression of HIF-1alpha without a time-dependent way was also detected in full thickness of the right ventricle in occurrence of ventricular arrhythmia after LAD ligation., Conclusion: HIF-1alpha may be regarded as a sensitive marker for sudden cardiac death induced by early acute myocardial ischemia, and may also be helpful for the diagnosis of fatal arrhythmia.

Objective: To investigate the immunohistochemical distributions and expressions of vascular endothelial growth factor (VEGF) in the model of rat myocardial ischemia., Methods: The model of myocardial ischemia was established by ligating the left anterior descending (LAD) coronary artery of rats. The changes of VEGF expression were detected by immunohistochemistry and Western blot at time points after myocardial ischemia. The electrocardiographic changes were evaluated uninterruptedly., Results: The expression of VEGF was not be found in control group. Fifteen minutes after LAD ligation, weak positive expression of VEGF were found in the ischemic myocardium. The expression of VEGF reached the peak at 3 hours after ligation. The VEGF distribution was mainly localized in the ischemic and peri-ischemic regions. Six hours after LAD ligation, the expression of VEGF decreased comparing with 3 hours and showed a relatively higher level. Fatal arrhythmia was found in nine rats by the electrocardiograph., Conclusion: The immunohistochemical staining of VEGF could be helpful for investigating the location and severity of acute myocardial ischemia. Fatal arrhythmia may be secondary to myocardial ischemia.

Methamphetamine (MA) is a representative drug of amphetamine-type stimulants for central nervous system and has become one of the most dangerous drugs in the world recently. The present article reviews the pharmacological effects, distribution, metabolism, intoxication mechanism, the effects of MA on cardiovascular and central nervous systems of MA, and the current situation of forensic investigation on MA.

In the title compound, [Fe(4)(C(6)H(12)N(2)S(4))(C(18)H(15)P)(2)(CO)(10)], the unit cell contains one mol-ecule, which exhibits a crystallographically imposed center of symmetry. The independent Fe(2)S(2) fragment [Fe-Fe = 2.527 (1) Å] is in a butterfly conformation, and each Fe atom displays a pseudo-square-pyramidal coordination geometry. The phosphane group occupies an apical position [Fe-P = 2.2670 (14) Å]. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into chains along [110].

Brain natriuretic peptide (BNP) is a major marker for evaluating cardiac function and has been widely used in clinical practice. Recent researches show that BNP is also useful for identification of sudden cardiac death in forensic pathology. This article reviews the molecular structure and biological characteristics of the BNP and its application as a functional indicate in forensic medicine. It shows that the expression of BNP in cardiac muscles, together with the expression of BNP in blood and pericardium liquid can be used to evaluate the pathological physiology changes and dysfunction degrees of the heart during the cardiac sudden death.

Objective: To explore the characteristics of autopsy cases of anaphylactic shock induced by cephalosporins and provide the evidences in forensic medicine., Methods: Twenty cases of anaphylactic shock induced by cephalosporins were collected from April 2005 to August 2009 in judicial expertise center of China Medical University, and the characteristics of the cases were analyzed retrospectively., Results: The age of decedents ranged from 40 to 60 years. Ninety percent of cases were from local medical centers and private clinics. The symptoms of the shock appeared 30 s-150 min after the administration of the drug, and death occurred 10 min-210 min after the appearance of the shock symptoms. In all cases, various degrees of eosinophil infiltration were observed in trachea and the lungs. Serum IgE detected by ELISA method was normal value in 14 cases., Conclusion: In fatal anaphylactic cases, little specific findings are detected during postmortem and microscope examination. For this reason, the determination of cause of death in these cases requires comprehensive analysis combined with clinic information and excludes other diseases leading to the sudden death.

Objective: To investigate the maximum resistance strength of a new orthodontic anchorage system named bone-bonding screw., Methods: Thirty-six self-designed two-section bone-bonding screws were bonded to the surface of tibia in 12 rabbits with N-2-butyl cyanoacrylate. The maximum resistance strength of the screws was tested immediately, 2 weeks, 4 weeks and 8 weeks after bonding, respectively., Results: The average maximum resistance strengths of the bone-bonding screws immediately, 2 weeks, 4 weeks and 8 weeks after bonding were 11.55 (8.96, 12.73), 6.04 (1.88, 10.57), 2.30 (0, 3.24), and 49.85 (20.70, 66.01) N, respectively. The difference between each group was statistically significant (P < 0.05). The failure rate of the bone-bonding screws was 17% (6/36)., Conclusions: The maximum resistance strength of the bone-bonding screw could suffice for orthodontics.

Aim: To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma., Methods: Methylation-specific polymerase chain reaction (MSPCR) was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease (30 with benign gastric disease and 30 with benign colorectal disease), and 30 healthy donor controls. A paired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postoperative serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy., Results: The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric (34.0%) and colorectal (28.9%) adenocarcinoma patients were significantly higher than those in patients with benign gastric (3.3%) or colorectal (6.7%) disease or in healthy donors (0%) (P < 0.01). The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis., Conclusion: Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.

Objective: To study the change of Ca2+ density in cultured osteoclast-like cells in response to fluid shear stress., Methods: Laser scanning confocal microscope and fluorescent probe were used to detect the free Ca2+ in osteoclast-like cells before and after undergoing fluid shear stress. The images were analyzed and compared with image software., Results: At 37 degrees C the free Ca2+ in osteoclast-like cells could be labelled effectively with 10 micromol/L Fluo-3/AM. Compared with contol group, the average intensity of Ca2+ fluorescent signal in osteoclast-like cells undergoing fluid shear stress increased significantly., Conclusion: The Cal2+ concentration in bone-marrow derived osteoclast-like cells is sensitive to fluid shear stress, which suggests osteoclast-like cells modulate their function in response to fluid shear stress through the change of free Ca2+ concentration.

Traumatic brain injury (TBI) is the most common cause of traumatic death in infancy, and inflicted TBI (iTBI) is the predominant cause. Like other central nervous system pathologies, TBI changes the composition of cerebrospinal fluid (CSF), which may represent a unique clinical window on brain pathophysiology. Proteomic analysis, including two-dimensional (2-D) difference in gel electrophoresis (DIGE) combined with mass spectrometry (MS), was used to compare the CSF protein profile of two pooled samples from pediatric iTBI (n = 13) and non-inflicted TBI (nTBI; n = 13) patients with severe injury. CSF proteins from iTBI and nTBI were fluorescently labeled in triplicate using different fluorescent Cy dyes and separated by 2-D gel electrophoresis. Approximately 250 protein spots were found in CSF, with 90% between-gel reproducibility of the 2-D gel. Following in-gel digestion, the tryptic peptides were analyzed by MS for protein identification. The acute phase reactant, haptoglobin (HP) isoforms, showed an approximate fourfold increase in nTBI versus iTBI. In contrast, the levels of prostaglandin D(2) synthase (PGDS) and cystatin C (CC) were 12-fold and sevenfold higher in iTBI versus nTBI, respectively. The changes of HP, PGDS, and CC were confirmed by Western blot. These initial results with conventional gel-based proteomics show new protein changes that may ultimately help to understand pathophysiological differences between iTBI and nTBI.

The etiology of lung cancer in population with little or no tobacco exposure is not well understood. Individual genetic susceptibility factors have been suggested to contribute to lung cancer risk in this population. Mutations in the p53 tumor suppressor gene are implicated in the development of lung cancer as they are frequently found in lung tumors from both smokers and never-smokers. In order to determine whether genetic polymorphisms affecting DNA repair capacity modulate p53 mutations in lung tumors from never-smokers, we compared p53 mutations with genotypes of XPD 312, XPD 751, and XRCC1 399 in lung tumors from 43 lifetime never-smokers. p53 mutations were identified in 10 (23%) cases and consisted mostly of G/C to A/T transitions. No statistically significant association was found between p53 mutations and genotypes of XPD 312 or XPD 751. However, patients with the XRCC1 399 Gln allele, that results in a lower base excision repair capacity, were more likely to have p53 mutations, compared with patients the wild-type Arg allele (P = 0.03). In addition, the p53 mutation frequency increased with an increasing number of combined genotypes associated with a lower DNA repair capacity of XPD 312, XPD 751, and XRCC1 399 (P = 0.02). These results suggest that individuals who never smoked and had XRCC1 399 Gln allele may be at a greater risk of p53 mutations, especially if combined with the genotypes of XPD 312 and XPD 751 that may result in a lower DNA repair capacity.

Posttranslational modifications (PTMs) of histone proteins may result in altered epigenetic signaling after pediatric traumatic brain injury (TBI). Hippocampal histone H3 acetylation and methylation in immature rats after moderate TBI were measured and decreased only in CA3 at 6 h and 24 h with persistent methylation decreases up to 72 h after injury. Decreased histone H3 acetylation and methylation suggest altered hippocampal CA3 epigenetic signaling during the first hours to days after TBI.

Traumatic brain injury (TBI) to postnatal day 17 rats has been shown to produce acute changes in hippocampal global protein levels and spatial learning and memory deficits. The purpose of the present study was to analyze global hippocampal protein changes 2 weeks after a moderate ipsilateral controlled cortical impact in postnatal day 17 rats using 2-dimensional difference gel electrophoresis and mass spectrometry. Paired sham and ipsilateral injured hippocampal lysates were independently labeled with different fluorescent cyanine dyes and coseparated within the same immobilized pH gradient strips and slab gel based on isoelectric point and molecular mass. Significant changes in key proteins involved in glial and neuronal stress, oxidative metabolism, calcium uptake and neurotransmitter function were found 2 weeks after injury, and their potential roles in hippocampal plasticity and cognitive dysfunction were discussed., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response., Methods: Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance., Results: Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and alpha-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified., Conclusion: Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.

Lung cancer mortality rates in the Xuan Wei County population are among the highest in China and are associated with exposure to indoor emissions from the burning of smoky coal. Previous studies of lung tumors from both non-smoking women and smoking men in this region showed high frequencies of mutations, consisting mostly of G-->T transversions in the p53 tumor suppressor gene and K-ras oncogene, suggesting that these mutations were caused primarily by polycyclic aromatic hydrocarbons. In this study sputum samples from 92 individuals with no evidence of lung cancer from Xuan Wei County were screened for p53 and K-ras mutations. Sputum cells were collected on glass slides by sputum cytocentrifugation, stained and cytopathologically analyzed. Cytologically non-malignant epithelial cells were taken from each sputum sample using a laser capture microdissection microscope and molecularly analyzed. Cells taken from the sputum of 15 (16.3%) individuals were mutation positive, including 13 (14.1%) individuals each with a p53 mutation, 1 (1.1%) individual with a K-ras mutation and 1 (1.1%) individual with a p53 and a K-ras mutation. p53 mutations were found in both the sputum of individuals with evidence of chronic bronchitis (3 of 46 or 6.5%) and those without evidence of this disease (11 of 46 or 23.9%). Therefore, mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent in non-malignant epithelial cells taken from the sputum of individuals without evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei County and were at a high risk for developing the disease.

Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the implication of p53 mutations in breast cancer development remains poorly understood. In this study, we applied laser capture microdissection (LCM) microscope to histologically review and sample cells from paraffin-embedded breast tissue sections obtained from six cases of ductal carcinoma in situ (DCIS) and ten cases of atypical ductal hyperplasia (ADH). p53 mutations were detected, using single stranded conformational polymorphism (SSCP) and sequencing, in cell samples of three cases with DCIS and five cases with ADH. p53 mutations are therefore present in DCIS and ADH of the breast, considered as pre-malignant precursors to breast cancer, and some of them may represent early events in breast cancer development.

Mutations in the p53 tumor suppressor gene and the K-ras oncogene have been frequently found in sputum and bronchoalveolar lavage (BAL) samples of lung cancer patients and other patients prior to presenting clinical symptoms of lung cancer, suggesting that they may provide useful biomarkers for early lung cancer diagnosis. However, the detection of these gene mutations in sputum and BAL samples has been complicated by the fact that they often occur in only a small fraction of epithelial cells among sputum cells and, in the case of p53 gene, at many codons. In this study, sputum cells were collected on a filter membrane by sputum cytocentrifugation and morphologically analyzed. Epithelial cells were selectively taken by using a laser capture microdissection microscope and analyzed by polymerase chain reaction (PCR) and single-stranded conformational polymorphism (SSCP) for p53 mutations and by PCR and denaturing gradient gel electrophoresis (DGGE) for K-ras mutations. This method was used to analyze sputum of 15 Chinese women with lung cancer from Xuan Wei County, China and detected mutations in sputum of 7 (46.7%) patients, including 5 patients with p53 mutations, 1 patient with a K-ras mutation, and 1 patient with K-ras and p53 mutations. For comparison, only two of the mutations were detected by conventional methods. Therefore, the laser capture/mutation analysis method is sensitive and facilitates the detection of low-fraction mutations occurring throughout the p53 and K-ras genes in sputum of lung cancer patients. This method may be applicable to the analysis of epithelial cells from clinically normal sputum or BAL samples from individuals with a high risk for developing lung cancer.

Lung cancer, a disease related mostly to tobacco smoke exposure and a leading cause of cancer-related death in industrialized countries, is frequently associated with mutations in the p53 tumor suppressor gene. Genetic differences resulting in inter-individual variation in DNA repair capacity may in part account for susceptibility of a cell to genotoxic agents leading to somatic mutations, including p53 mutations, and eventual transformation of a normal cell into a malignant phenotype. The objective of this study is to investigate the relationship between the polymorphisms of two DNA repair genes, the nucleotide excision repair xeroderma pigmentosum group D (XPD) gene (codons 312 and 751) and the base excision repair X-ray repair cross-complementing group 1 (XRCC1) gene (codon 399), and p53 mutations among lung cancer patients. Lung tumors from 204 smokers with non-small cell lung cancer (NSCLC) were analyzed for mutations in exons 5-8 of the p53 gene and genotypes of XPD and XRCC1. p53 mutations were found in 20% (40/204) of the patients. Patients with the XPD codon 312 Asn allele were less likely to have p53 mutations (13.8%) than XPD 312 Asp/Asp (27.3%) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.20-0.89, P = 0.023]. No association was found between p53 mutations and either XPD Lys751Gln or XRCC1 Arg399Gln. However, the p53 mutation frequency increased with the increased number of the combined genotypes among XPD 312WT (Asp/Asp), XPD 751VT (Lys/Gln or Gln/Gln) or XRCC1 399VT (Arg/Gln or Gln/Gln) (P = 0.01, trend test). These results suggest that individuals who smoke and have the XPD codon 312 Asp/Asp genotype may be at a greater risk of p53 mutations, especially if combined with other polymorphisms that may result in deficient DNA repair.

Lung cancer mortality rate in nonsmoking women in Xuan Wei (XW) County is the highest in China. The XW lung cancer rate is associated with exposure to coal smoke, containing high concentrations of polycyclic aromatic hydrocarbons (PAHs), in unvented homes. Here we investigated codon 12 K-ras mutations in lung tumors or sputum samples from 102 XW lung cancer patients (41 nonsmoking women and 61 smoking men). In addition, we analyzed specimens from 50 lung cancer patients (14 nonsmoking women, 33 smoking men and three nonsmoking men), from Beijing and Henan (B&H), where natural gas is the main domestic fuel. K-ras mutations were found in nine women (21.9%) and 14 men (22.9%) from XW, with G to T transversions accounting for 66.7 and 85.7%, respectively. Among B&H patients, one woman (7.1%) and six men (16.7%) had K-ras mutations, with G to T transversions accounting for 66.7% of the mutations in the men. Therefore, the frequency and type of K-ras mutations in XW nonsmoking women are similar to those of K-ras mutations found in both XW and B&H smoking men. On the other hand, the mutation frequency in XW women is higher than, although not statistically significant from, that in the B&H nonsmoking women (P=0.28, two-sided Fisher's Exact Test). These results suggest an association between exposure to coal smoke and the increased K-ras mutation frequency in XW nonsmoking female lung cancer patients. They also suggest that the mutagens and/or mechanisms of mutations in these nonsmoking women are similar to those responsible for K-ras mutations in cigarette smoking lung cancer patients, which are probably induced largely by chemicals such as PAHs.

The p53 gene is frequently mutated in lung tumors, and mutations may be caused by both polycyclic aromatic hydrocarbons (PAHs) and nitrosamines found in tobacco smoke. The two major forms of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SCC), are known to differ in the proportion of tumors exhibiting p53 mutation, and may also differ in the mutational spectra produced. Previous studies comparing p53 mutational spectra between AC and SCC of the lung have been limited by small sample size. We examined p53 mutations in exons 5-8 in 202 cases of AC and 82 cases of SCC from smoking lung cancer patients in the Western Pennsylvania region. The percent of cases with p53 mutation was significantly lower in ACs (40/202, 20%) compared to SCCs (29/82, 35%, P=0.006). The proportion of mutations present that were G to T transversions was not significantly different between the two tumor types (52% of p53 mutations in AC compared to 32% in SCC). G to A transitions either did not differ in frequency in the two types of lung cancer (20% of mutations in AC and 24% of mutations in SCC). A distinct spectrum was observed, however, in the p53 mutation pattern in the two types of lung cancer. ACs showed a strong preference for a mutational hotspot at codons 248 and 249, while squamous cell tumors showed mutational events spread throughout exons 5-8, with a preference for codon 267. Mutations at codon 267 in SCC were all C to T transitions that occurred at CpG sites. Both tumor types demonstrated preferential mutation of the non-transcribed strand (100% of all G to T transversions and 55% of the G to A transitions). These results suggest that p53 mutations in both types of lung tumors may arise from adduction by both PAHs and nitrosamines. Mutations arising in ACs appear selectively in regions of p53 that produce more rigid proteins, suggesting a drastic change in p53 function is needed to result in ACs, while less constrained changes in p53 function can result in SCCs. Mutation in p53 was not found to be related to patient survival in this group of patients, while tumor size and degree of differentiation were poor survival predictors.