Short-term associations of particulate matter with different aerodynamic diameters with mortality due to mental disorders and dementia in Ningde, China.

Limited evidence is available regarding the impact of ambient inhalable particulate matter (PM) on mental disorder (MD) or dementia-related deaths, particularly PM1, PM1-2.5, and coarse particles (PM2.5-10). Moreover, individual confounders have rarely been considered. In addition, evidence from low-pollution areas is needed but is inadequate. Using death records from the Death Registration System during 2015-2021 in Ningde, a coastal city in southeast China, we combined a conditional quasi-Poisson model with a distributed lag nonlinear model to estimate the nonlinear and lagged associations of PM exposure with MD or dementia-related deaths in Ningde, China, comprehensively controlling for individual time-invariant confounders using a time-stratified case-crossover design. The attributable fraction and number were calculated to quantify the burden of MD or dementia-related deaths that were related to PMs. We found J-shaped relationships between MD or dementia-related deaths and PMs, with different thresholds of 13, 9, 19, 33 and 12 µg/m3 for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10. An inter-quartile range increase for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 above the thresholds led to an increase of 31.8% (95% confidence interval, 14.3-51.9%), 53.7% (22.4-93.1%), 32.6% (15.0-53.0%), 35.1% (17.7-55.0%) and 25.9% (13.0-40.3%) in MD-related deaths at lag 0-3 days, respectively. The associations were significant in the cool season rather than in the warm season and were significantly greater among people aged 75-84 years than in others. The fractions of MD-related deaths attributable to PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 were 5.55%, 6.49%, 7.68%, 10.66%, and 15.11%, respectively; however, only some of them could be protected by the concentrations recommended by the World Health Organisation or China grade I standard. Smaller associations and similar patterns were observed between PMs and dementia-related death. These findings suggest stricter standards, and provide evidence for the development of relevant policies and measures.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.

Short sleep duration is associated with increased risk of pre-hypertension and hypertension in Chinese early middle-aged females.

PURPOSE: The aim of this study is to investigate the relationship between sleep duration and hypertension in a middle-aged Chinese population. METHODS: Cross-sectional data of 20,505 individuals aged 35-64 years from Taizhou longitudinal study was used. Logistic regression models were used to calculate odds ratios (ORs) for the risk of pre-hypertension and hypertension in association with sleep duration. RESULTS: Short sleep duration was associated with high systolic and diastolic blood pressure in comparison with sleep duration of 7-8 h in females. Short sleep duration was also associated with an increased risk of hypertension in females. Age-stratified analysis showed that as compared with sleep duration of 7-8 h, sleep duration <6 h increased risk of hypertension after controlling for multiple covariates with an OR of 1.766 (1.024-2.775) in early middle-aged females of 35-44 years. More importantly, sleeping less than 6 h is associated with increased risk of pre-hypertension in females of this age category, after controlling for multiple covariates with an OR of 1.769 (1.058-2.958). CONCLUSIONS: Sleeping less than 6 h a day is associated with increased risk of pre-hypertension and hypertension in Chinese early middle-aged females. The high-risk populations require sufficient sleep, which could probably prevent the increased risk of pre-hypertension as well as hypertension.

Mechanical properties of municipal solid waste under different stress paths: Effects of plastic content and particle gradation.

Plastics within municipal solid waste (MSW) are non-degradable. As MSW continues to degrade, the relative content of plastics rises, and particle gradation may also change. Moreover, throughout the landfilling process, MSW is subjected to various stress conditions, potentially influencing its mechanical properties. This study explored the effects of varying plastic contents, different particle gradations, and distinct stress paths on the mechanical properties of MSW, and consolidated drained triaxial tests of 42 groups of reconstituted MSW specimens were conducted. The results showed that there was an optimal plastic content of 6-9 % for MSW, where the shear strength of MSW was higher than that of MSW with other plastic contents. When the stress path changed from TC45 to TC72, the optimal plastic content of MSW changed from 6 % to 9 %. As the plastic content increased, both the cohesion and internal friction angle of the MSW initially increased, then subsequently decreased. The impact of plastic content on cohesion was more pronounced than on the internal friction angle, especially at larger strains. Under various stress paths, MSW with distinct particle size distributions demonstrated diverse stress-strain behaviors. Traditional criteria for evaluating well-graded conditions in soils are not suitable for MSW. The effect of gradation on the cohesion of MSW is essentially due to the predominant role of fiber content; the relationship between gradation and the internal friction angle in MSW is complex and correlates closely with the content of both coarse and fine particles, as well as fibers. This study serves as an essential reference for predicting deformations in landfills and analyzing the stability of landfill slopes.

On-site monitoring and numerical simulation on groundwater flow and pollution plume evolution in a hexavalent-chromium contaminated site.

Accurately ascertaining spatiotemporal distribution of pollution plume is critical for evaluating the effectiveness of remediation technologies and environmental risks associated with contaminated sites. This study concentrated on a typical Cr(VI) contaminated smelter being currently remediated using pump-and-treat (PAT) technology. Long-term on-site monitoring data revealed that two highly polluted regions with Cr(VI) concentrations of 162.9 mg/L and 234.5 mg/L existed within the contaminated site, corresponding to previous chromium slag yard and sewage treatment plant, respectively. The PAT technology showed significant removal performance in these highly polluted areas (>160 mg/L) after six months of pumping, ultimately achieving complete removal of the pollutants in these high-pollution areas. Numerical simulation results showed that although the current remediation scheme significantly reduced the Cr(VI) pollution degree, it did not effectively prevent the incursion of the pollution plume into the downstream residential area after 20 years. Additionally, an improved measure involving supplementary pumping wells was proposed, and its remediation effects were quantitatively evaluated. Results indicated that the environmental pollution risk of groundwater downstream could be effectively mitigated by adding pumping wells, resulting in a reduction of the pollution area by 20 % in the case of adding an internal well and 41 % with the addition of external wells after 20 years. The findings obtained in this study will provide an important reference and theoretical guidance for the reliability analysis and design improvement of the PAT remediation project.

Design of ultrathin plasmonic quarter-wave plate based on period coupling.

Based on an analysis of the surface admittance of a plasmonic film with a substrate, we propose an ultrathin quarter-wave plate consisting of a periodic plane array of symmetrical L-shaped plasmonic antennas. The period, which determines the coupling among L-shaped antennas, is an important parameter for optimizing the performance of the structure. Numerical simulation results show that an Au quarter-wave plate designed in this Letter can efficiently convert a linearly polarized light at normal incidence into circularly polarized light, whose ellipticity is 0.994 at an operating wavelength of 1550 nm. The thickness is only 30 nm, which is nearly 1/50 of the wavelength of incident light.

Machine learning-based models for predicting gas breakthrough pressure of porous media with low/ultra-low permeability.

Gas breakthrough pressure is a significant parameter for the gas exploration and safety evaluation of engineering barrier systems in the carbon dioxide storage, remediation of contaminated sites, and deep geological repository for disposal of high-level nuclear waste, etc. Test for determining gas breakthrough pressure is very difficult and time-consuming, due to the low/ultra-low conductivity of the specimen. It is also difficult to get a comprehensive and high-precision model based on limited results obtained through individual experiments, as the measurements of gas breakthrough pressure were influenced by many factors. In this study, a collected database was built that covered a lot of former test data, and then, two models were developed by the random forest (RF) algorithm and multiexpression programming (MEP) method. The MEP model constructed with explicit expressions for the gas breakthrough pressure overcame the drawbacks of common "black box" models. Meanwhile, five significant indicators were selected from ten common features using the permutation importance algorithm. The RF model was interpreted by the Shapley value and the PDP/ICE plots, while the MEP model was analyzed through the proposed explicit expression, showing strong consistence with that in former studies. Finally, robustness analysis was conducted, and stability of the proposed two models was verified.

Laboratory investigation on the retention performance of a soil-bentonite mixture used as an engineered barrier: insight into the effects of ionic strength and associated heavy metal ions.

Soil-bentonite (S-B) materials are promising backfill materials for use as engineered barriers in heavy metal-contaminated sites. The effects of contaminant exposure on the retention performance of the S-B barrier remain unrevealed. In this study, based on the pollution status of an abandoned ferroalloy factory located in southern China, the retention performance of the S-B mixture toward Cr(VI) and Zn(II) was studied through adsorption and diffusion experiments sequentially; the separate effect of ionic strength (binary solution) and the combined effect of ionic strength and associated heavy metal ion (ternary solution) were discussed. In NaCl-Cr(VI)/Zn(II) binary solutions, the adsorption of Zn(II) onto the S-B mixture is larger than that of Cr(VI). Kd, Qmax, and ɛacc (accessible porosity) of Cr(VI) increase through increasing ionic strength, while Zn(II) shows the opposite trend; De (effective diffusion coefficient) values for both Cr(VI) and Zn(II) increased with increasing ionic strength and follow a sequence of Cr(VI) > Zn(II), indicating a better retention performance of the S-B mixture to Zn(II). For a given ionic strength, the adsorption of Zn(II) was larger than that of Cr(VI), which can be attributed to the retention specificity of the S-B mixture to anion and cation. In Cr(VI)-Zn(II)-NaCl ternary solutions, the adsorptions of Cr(VI) and Zn(II) are enhanced in varying degrees when compared with their binary solution, which probably could be attributed to the ion bridge role of Cr(VI)/Zn(II) to connect each other that relatively increased the adsorption capacity of S-B material. This work will contribute to an in-depth understanding of the retention performance of the S-B mixture in complicated chemical environments and facilitate the selection of future remediation strategies.

Spatiotemporal distribution and pollution control of pollutants in a Cr(VI)-contaminated site located in Southern China.

Soil and groundwater Cr(VI) pollution resulting from improper disposal and accidental spills is a critical problem worldwide. In this study, a comprehensive study was conducted to assess the hydrogeological conditions of a contaminated site, obtain spatiotemporal distribution and trend forecasts of pollutant Cr(VI), and determine the feasibility of applying clayey engineered barriers for pollution control. The results showed that the hydraulic conductivity (K) of the clayey barrier (1.56E-5 m/d) is several orders of magnitude lower than that of the stratum beneath the contaminated site, with K values ranging from 0.0014 to 4.76 m/d. Cr(VI) exhibits high mobility and a much higher concentration in the vadose zone, with maximum values of 6100 mg/kg in topsoil and 2090 mg/L in the perched aquifer. The simulation results indicated that the groundwater in the vicinity of the contaminated site, as well as downstream of the Lianshui River, is seriously threatened by Cr(VI). Notably, the pollution plume could occur downstream of the Lianshui River after 8 years. The retention efficiency of clayey engineered barriers will decrease over time, at 61.6% after 8 years and 33% after 20 years. This work contributes to an in-depth understanding of Cr(VI) migration at contaminated sites.

Improving the room-temperature confinement of light by miniaturizing mode sizes into a deep subwavelength scale using dielectric spheres in metal cavities.

The confinement of light within nanometer-scale regions may result in the significant enhancement of light-matter interactions. However, light confinement to nanometers is hindered by the diffraction limit of a dielectric material. For a dielectric cavity, if the material loss is negligible, reducing the cavity size usually causes a significantly increase in radiation loss. Surface plasmons show great promise for potential subwavelength light confinement. However, in most circumstances, light confinement by dissipative metallic materials can cause ohmic losses at optical frequencies. In such cases, the realization of light confinement with deep subwavelength mode sizes results in great losses and thus has low quality factors. In the present study, a three-dimensional light confinement with deep subwavelength mode sizes is achieved using dielectric spheres in metal cavities. Contrary to other mechanisms for subwavelength light confinement that are based on the use of dielectric or metal cavities, the nanometer-scale regions ensure that most of the light energy is confined away from the metal-dielectric interfaces, thereby decreasing light absorption in the metal cavity. In turn, the metal cavity decreases the radiation loss of light. Thus, high quality factors ranging from 2×10(2) to 6×10(2) can be obtained at room temperature. An effective electrical mode volume ranging from 7×10(-5)λ(0)(3) to 2×10(-4)λ(0)(3) (where λ(0) is the resonant wavelength in a vacuum) can be achieved. Therefore, this method of three-dimensional light confinement with deep subwavelength mode sizes using dielectric spheres in metal cavities may have potential applications in the design of nanolasers, nanophoton detectors, nonlinear optical switches, and so on.

Wave propagation in deep-subwavelength mode waveguides.

This Letter proposes a dielectric waveguide with deep-subwavelength mode sizes. Results of both frequency domain and time domain analysis show that the effective mode area is below λ(0)(2)/400 and can even reach λ(0)(2)/1000 (λ(0) is the wavelength in vacuum). The effective electrical mode area can be comparable to that of a hybrid plasmonic subwavelength confinement waveguide, with reduced optical absorption. In contrast to slot waveguides, which guide light in low-index materials, the proposed structure guides light in high-index materials. Results obtained in this Letter show that the losses are sensitive to the surface roughness on the tens of nanometers scale. The structure can be used to design ring resonators with a quality factor comparable to that of a diffraction-limited dielectric ring resonator with the same standing wave numbers. The property can be applied in nonlinear effect enhancement or laser design with ultralow threshold.

Identification of multiple single-nucleotide variants for clinical evaluation of Helicobacter pylori drug resistance.

Helicobacter pylori infections are threats to public health due to their high infection rate and drug resistance. Identification of single-nucleotide variants (SNVs) in H. pylori is crucial for both diagnosis and therapy. Yet the clinical testing of resistant H. pylori mutants is still facing some challenges, such as the selectivity is not good enough for SNVs in abundant wild-type DNA, the lack of clinical validation and the economical burden on patients. Herein, an X-shaped DNA probe with a toehold initiator was designed, which could specifically hybridize with certain genotype DNA due to the thermodynamically driven reaction. A competitive reaction was developed to amplify the thermodynamic difference between wild-type DNA and SNVs, diminishing the interference of wild-type DNA. By this means, multiple SNVs in H. pylori were successfully identified and two SNVs related to clarithromycin resistance are chosen as model targets. A paper strip was fabricated for visual, fast screening of SNVs. Furthermore, the approach was validated using clinical samples, and a point-of-care (POCT) testing diagnosis was executed on saliva samples, demonstrating its potential for the prevention and cure of H. pylori infections.

Unidirectional transmission realized by two nonparallel gratings made of isotropic media.

We realize a unidirectional transmission by cascading two nonparallel gratings (NPGs) made of isotropic, lossless, and linear media. For a pair of orthogonal linear polarizations, one of the gratings is designed as a polarizer, which is a reflector for one polarization and a transmitter for the other; another grating is designed as a polarization converter, which converts most of one polarized incident wave into another polarized transmitted wave. It is demonstrated by numerical calculation that more than 85% of the incident light energy can be transmitted with less than 1% transmission in the opposite direction for linearly polarized light at normal incidence, and the relative bandwidth of the unidirectional transmission is nearly 9%. The maximum transmission contrast ratio between the two directions is 62 dB. Unlike one-way diffraction grating, the transmitted light of the NPGs is collinear with the incident light, but their polarizations are orthogonal.

Analysis of Immunological Characteristics and Genomic Alterations in HPV-Positive Oropharyngeal Squamous Cell Carcinoma Based on PD-L1 Expression.

Programmed death-ligand 1 (PD-L1) expression has been approved as an immune checkpoint inhibitor (ICI) response predictive biomarker; however, the clinicopathological and molecular features of HPV-positive oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] based on PD-L1 expression are not well studied. We aimed to characterize clinicopathological, tumor immune microenvironmental, and molecular features of HPV(+)OPSCC with different PD-L1 expression scored by combined positive score (CPS). A total of 112 cases were collected from 2008-2021 and received PD-L1 and CD8 immunohistochemistry (IHC) staining. 71 samples received DNA sequencing out of which 32 samples received RNA sequencing for immune-related gene alterations or expression analysis. The 32 samples were also subjected to analysis of CD20, CD4, CD8, CD68, Foxp3 and P16 by multiplex immunofluorescence (mIF) staining, and the immune markers were evaluated in the tumor body (TB), tumor margin (TM) and normal stroma (NS) regions separately. Our results showed that of 112 HPV(+)OPSCC tumors, high(CPS≥20), intermediate(1≤CPS<20), and low(CPS<1) PD-L1 expression was seen in 29.5%, 43.8% and 26.8% cases respectively. Non-smoking patients and patients with tumors occurring at the tonsils or having rich lymphocytes infiltration had significantly higher PD-L1 expression. Patients with CPS≥20 had significantly higher tumor mutation burden (TMB, p=0.0058), and PD-L1 expression correlated significantly with CD8+ T cells infiltration, which were ample in tumor regions than in NS in mIF. CD20+, CD4+, CD68+, Foxp3+CD4+ cells were demonstrated to infiltrate higher in TM while CD20+ and CD68+ cells were also enriched in NS and TB regions respectively. However, none of them showed correlations with PD-L1 expression. ARID1A, STK11 alterations were enriched in the low PD-L1 group significantly, while anti-viral immune associated APOBEC mutation signature and immune-related genes expression such as XCL1 and IL11 were positively associated with PD-L1 expression (p<0.05). This is a comprehensive investigation revealing immune and molecular features of HPV(+)OPSCC based on PD-L1 expression. Our study suggested that 73.2% of HPV(+)OPSCC patients may benefit from immunotherapy, and high PD-L1 expression reflects immune-active status of HPV(+)OPSCC accompanied by higher immune effect factors such as TMB, CD8+ cytotoxic T cells and immune-related genomic alterations. Our study offers valuable information for understanding the immune features of HPV(+)OPSCC.

Unidirectional transmission in non-symmetric gratings made of isotropic material.

We achieve a broadband unidirectional transmission or One-way diffraction grating by cascading two parallel gratings made of isotropic material with different periods. In order to significantly reduce the reciprocal transmission of the zero order, one of them is chosen to be a subwavelength grating and designed as a wideband reflector for the incident-wave. It is demonstrated that more than 65 percent of the incident-wave energy can be transmitted unidirectionally with less than 0.22 percent transmission in the opposite direction at normal incidence for TE polarization. And, the relative bandwidth of the unidirectional transmission is greater than 10 percent.

The sorption performance of corroded Gaomiaozi bentonite by evolved cement water at different temperatures: the case of europium removal.

In the Chinese high-level radioactive waste geological disposal program, Gaomiaozi (GMZ) bentonite has been selected as the potential buffer/backfill material. After the closure of the repository, the Ca-OH-type alkaline solution (evolved cement water) released by cement degradation may last for more than 100,000 years. The bentonite will undergo the corrosion of evolved cement water (ECW) for a long period. This work focuses on the sorption property of GMZ bentonite altered by ECW. Firstly, the corrosion experiments on compacted GMZ specimens with the dry density of 1.70 Mg/m3 were carried out under constant volume conditions at two temperatures. Then, the sorption of europium (Eu (III)) onto the corroded GMZ bentonite was studied by batch experiments. The results of batch sorption tests indicate that the altered GMZ bentonite keeps an effective removal property with the uptake of Eu (III) more than 99%. The effect of high-temperature conditions of the repository on the sorption property of bentonite is not significant. The results also suggest that the evolved cement water presents no detrimental effect on the long-term adsorption performance of bentonite even under higher temperature conditions.

Intralesional injection of Pingyangmycin may be an effective treatment for epulis.

Gingival epulis represents a family of benign tumors and tumorlike masses of the gingiva. A spectrum of inflammatory and other reactive changes can be observed pathologically as granulation, fibrous or vascular tissue. It may occur at any age, but most commonly found in patients at their twenties and sixties. Women are more frequently affected than men. Surgical excision or removal is the treatment of choice, and wider resection including extraction of the involved teeth and adjacent tissues is often required in order to prevent recurrence. However, wider resection may result in cosmetic and functional problems. Epulis bears some similarities with hemangioma both clinically and histopathologically. Therefore, we hypothesize that intralesional injection of Pingyangmycin may be a safe and effective treatment for epulis. The efficacy of this treatment modality is worthy of further investigation.

Experimental and numerical study on heavy metal contaminant migration and retention behavior of engineered barrier in tailings pond.

Heavy metal pollution is a serious environmental problem globally, particularly in mines and tailings ponds. In this study, based on laboratory and field tests, the migration of heavy metal contaminants in a tailings pond and the retention behavior of a compacted bentonite engineered barrier system on the heavy metal contaminants were analyzed by a numerical simulation. The results demonstrate that the hydraulic conductivity of compacted bentonite is lower than that of the tailings from the laboratory tests. The hydraulic conductivity of the tailings sand decreased with an increase in the dry density and increased with an increase in the concentration of the chemical solution, which could be attributed to the large amounts of fine-grained soil contained in the tailings, according to the grain size distribution test. The hydraulic conductivity of the tailings from the engineering geological survey was between 2.0 × 10-6 and 9.0 × 10-5 m/s, and followed the order: tail coarse sand ＞ tail silty sand ＞ tail medium sand ＞ tail fine silt. The numerical simulation of the seepage could satisfactorily describe the actual working condition of the tailings dam. With the groundwater seepage, the migration range of the heavy metal contaminant in the researched tailings pond reached a maximum of 45 m for 5 years. The retention efficiencies of the 0.2 m engineered barrier against the heavy metal contaminant for 15 and 30 years were 45.4% and 57.2%, respectively. Moreover, the retention efficiency would exceed 87% when the engineered barrier thickness is increased to 0.5 m. The results of model validation show that the calculated results are in good agreement with the measured ones. These findings can provide effective ideas for the prevention and control of environmental pollution in mines and tailings ponds.

Calcitonin gene-related peptide enhances osteogenic differentiation and recruitment of bone marrow mesenchymal stem cells in rats.

The present study evaluated the effects of calcitonin gene-related peptide (CGRP) on bone marrow mesenchymal stem cells (BMMSCs) in vitro and in a rat model of mandibular distraction osteogenesis (MDO). Rat BMMSCs were isolated then treated with CGRP or CGRP antagonist (CGRP8-37). The proliferation and migration ability of BMMSCs was determined using 5-bromo-2'-deoxyuridine and Transwell assays, respectively. Osteogenic-related gene expression was analyzed with reverse transcription-quantitative polymerase chain reaction. For the in vivo analysis, thirty MDO rats were randomly assigned to control, CGRP or CGRP8-37 groups. To evaluate the mobilization of BMMSCs, nestin and stromal cell-derived factor 1 (SDF-1) were detected by immunohistochemistry and ELISA. Rats were sacrificed following 14 days and new bone formation was assessed by histological and micro-computed tomography analysis. In the in vitro results, the CGRP group demonstrated significantly higher migration and proliferation, as well as enhanced alkaline phosphatase and runt-related transcription factor 2 expression compared with the control. In the in vivo experiments, bone mineral density of the newly formed bone in the CGRP group was significantly higher than controls. The nestin and SDF-1 expression in the CGRP group was also significantly upregulated. In conclusion, the present study demonstrated that CGRP administration increased new bone formation, possibly via enhancing BMMSC migration and differentiation in MDO rats.

A new mutation of PTCH gene in a Chinese family with nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by a combination of development anomalies and a predisposition to tumour formation. Mutation of patched gene (PTCH), considered the molecular defect of NBCCS, in a Chinese NBCCS family was investigated in this study. METHODS: Genomic DNA was isolated from blood samples of all 12 members of this family. The mutated PTCH gene was screened by polymerase chain reaction amplification and direct sequencing. RESULTS: A new mutation of 3 bp (GAT deletion) was found in all seven affected members of this family. This mutation caused one aspartate deletion in the fourth transmembrane domain of the PTCH protein located within the sterol sensing domain (SSD). This deletion was not found in any unaffected members of this family nor in 200 control samples. CONCLUSIONS: Our findings suggest that one 3-bp deletion in PTCH gene was the cause of nevoid basal cell carcinoma in a Chinese family through affecting the conformation and function of PTCH protein.