GPX4-mediated bone ferroptosis under mechanical stress decreased bone formation via the YAP-TEAD signalling pathway.

Fracture of the alveolar bone resorption is a common complication in orthodontic treatment, which mainly caused by extreme mechanical loading. However, the ferroptosis with orthodontic tooth movement(OTM) relationship has not been thoroughly described. We here analysed whether ferroptosis is involved in OTM-associated alveolar bone loss. Mouse osteoblasts (MC-3T3) and knockdown glutathione peroxidase 4 (GPX4) MC-3T3 were stimulated with compressive force loading and ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and the changes in lipid peroxidation morphology, expression of ferroptosis-related factors and osteogenesis levels were detected. After establishing the rat experimental OTM model, the changes in ferroptosis-related factors and osteogenesis levels were reevaluated in the same manner. Ferroptosis was involved in mechanical stress regulating osteoblast remodelling, and Fer-1 and erastin affected osteoblasts under compression force loading. Fer-1 regulated ferroptosis and autophagy in MC-3T3 and promoted bone proliferation. GPX4-dependent ferroptosis stimulated the YAP (homologous oncoproteins Yes-associated protein) pathway, and GPX4 promoted ferroptosis via the YAP-TEAD (transcriptional enhanced associate domain) signal pathway under mechanical compression force. The in vivo experiment results were consistent with the in vitro experiment results. Ferroptosis transpires during the motion of orthodontic teeth, with compression force side occurring earlier than stretch side within 4 h. GPX4 plays an important role in alveolar bone loss, while Fer-1 can inhibit the compression force-side alveolar bone loss. GPX4's Hippo-YAP pathway is activated by the lack of compression force in the lateral alveolar bone.

Optimization of optical system for reducing tolerance sensitivity based on the high-order nodal aberration theory.

This paper proposes an optimization method aimed at addressing the challenge of balancing system imaging performance and tolerance performance. The method is based on the high-order nodal aberration theory. The calculation method for high-order aberration coefficients is derived, along with the change in aberrations after introducing tolerance perturbation. The evaluation system includes both the imaging performance of the system and its tolerance factors. A comprehensive merit function is created for optimization. Three aspherical system examples were designed for verification, and the optimization results of this method show significantly lower tolerance sensitivity compared to the general optimization results and the SAB function optimization results of CODE V.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

BACKGROUND: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. AIM: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). METHODS: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. OUTCOMES: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. RESULTS: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. CLINICAL IMPLICATIONS: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. STRENGTHS AND LIMITATIONS: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CONCLUSION: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.

OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Hierarchical classification for improving parcel-scale crop mapping using time-series Sentinel-1 data.

Parcel-scale crop classification utilizing time-series satellite observations is of significant importance in precision agriculture. The prior knowledge that crop types can be organized in a hierarchical tree structure is beneficial for improving crop classification. Moreover, the crop hierarchy aligns with the coarse-to-fine cognitive process of geographic scenes. Based on the crop hierarchy, this study developed a general hierarchical classification framework for enhancing crop mapping using time-series Sentinel-1 data. Central to this method is a deep-learning-based hierarchical classification model that explores and makes use of crop hierarchical knowledge. First, preprocessed Sentinel-1 data were geometrically overlaid onto farmland parcel maps to derive parcel-scale time-series features. Second, we constructed a hierarchical crop type system for study areas based on the crop phenology of labeled crop-type samples. Third, we developed a deep-learning-based hierarchical classification model to identify crop types for each parcel, to generate final crop-type classification maps. The proposed approach was further discussed and verified through the implementation of parcel-scale time-series crop hierarchical classifications in a study area in France with farmland parcel maps and time-series Sentinel-1 data. The classification results, indicating significant improvements greater than 4.0% in overall accuracy and 5.0% in F1 score over comparative methods, demonstrated the effectiveness of the proposed method in learning multi-scale time-series features for hierarchical crop classification utilizing Sentinel-1 data sequences.

Highland adaptation of birds on the Qinghai-Tibet Plateau via gut microbiota.

Highland birds evolve multiple adaptive abilities to cope with the harsh environments; however, how they adapt to the high-altitude habitats via the gut microbiota remains understudied. Here we integrated evidences from comparative analysis of gut microbiota to explore the adaptive mechanism of black-necked crane, a typical highland bird in the Qinghai-Tibet Plateau. Firstly, the gut microbiota diversity and function was compared among seven crane species (one high-altitude species and six low-altitude species), and then among three populations of contrasting altitudes for the black-necked crane. Microbiota community diversity in black-necked crane was significantly lower than its low-altitude relatives, but higher microbiota functional diversity was observed in black-necked crane, suggesting that unique bacteria are developed and acquired due to the selection pressure of high-altitude environments. The functional microbial genes differed significantly between the low- and high-altitude black-necked cranes, indicating that altitude significantly impacted microbial communities' composition and structure. Adaptive changes in microbiota diversity and function are observed in response to high-altitude environments. These findings provide us a new insight into the adaptation mechanism to the high-altitude environment for birds via the gut microbiota. KEY POINTS: • The diversity and function of gut microbiota differed significantly between the low- and high-altitude crane species. • Black-necked crane adapts to the high-altitude environment via specific gut microbiota. • Altitude significantly impacted microbial communities' composition and structure.

Detection method based on a coupled illumination correction algorithm for the detection of surface defects in ZrO2 ceramic bearing balls.

To address the problem of feature texture loss in defective images of zirconia bearing balls on unbalanced illumination backgrounds, a coupled algorithm of the local gamma function transform-block interpolation balancing equation is designed. A combination of a light reflection imaging model and a three-dimensional Gaussian surround function is used to extract the illumination estimate of the original image. Subsequent illumination balance correction is performed in the value color space. The contrast between the edges of the feature texture and the background is analyzed to construct a locally adaptive gamma function transformation model. We establish local block interpolation balance equations to eliminate the effects caused by illumination that is too high or too low. The experimental results show that the information entropy of the images after illumination correction changes in the range of 5% or less. The standard deviation and mean gradient can be increased by 15.21% and 14.78%, respectively.

Homocouplings of Sodium Arenesulfinates: Selective Access to Symmetric Diaryl Sulfides and Diaryl Disulfides.

Symmetrical diaryl sulfides and diaryl disulfides have been efficiently and selectively constructed via the homocoupling of sodium arenesulfinates. The selectivity of products relied on the different reaction systems: symmetrical diaryl sulfides were predominately obtained under the Pd(OAc)2 catalysis, whereas symmetrical diaryl sulfides were exclusively yielded in the presence of the reductive Fe/HCl system.

Construction and Verification of a Radiation Pneumonia Prediction Model Based on Multiple Parameters.

OBJECTIVE: Patients with lung cancer are at risk of radiation pneumonia (RP) after receiving radiotherapy. We established a prediction model according to the critical indicators extracted from radiation pneumonia patients. MATERIALS AND METHODS: 74 radiation pneumonia patients were involved in the training set. Firstly, the clinical data, hematological and radiation dose parameters of the 74 patients were screened by Logistics regression univariate analysis according to the level of radiation pneumonia. Next, Stepwise regression analysis was utilized to construct the regression model. Then, the influence of continuous variables on RP was tested by smoothing function. Finally, the model was externally verified by 30 patients in validation set and visualized by R code. RESULTS: In the training set, there was 40 patients suffered≥ level 2 acute radiation pneumonia. Clinical data (diabetes), blood indexes (lymphocyte percentage, basophil percentage, platelet count) and radiation dose (V15 > 40%, V20 > 30%, V35 >18%, V40 > 15%) were related to radiation pneumonia (P < 0.05). Particularly, stepwise regression analysis indicated that the history of diabetes, the basophils percentage, platelet count and V20 could be the best combination used for predicting radiation pneumonia. The column chart was obtained by fitting the regression model with the combined indicator. The receiver operating characteristic (ROC) curve showed that the AUC in the development term was 0.853, the AUC was 0.656 in the validation term. And calibration curves of both groups showed the high stability in efficiently diagnostic. Furthermore, the DCA curve showed that the model had a satisfactory positive net benefit. CONCLUSION: The combination of the basophils percentage, platelet count and V20 is available to build a predictive model of radiation pneumonia for patients with advanced lung cancer.

Effects of latanoprost on the expression of TGF-ß1 and Wnt / ß-catenin signaling pathway in the choroid of form-deprivation myopia rats.

In this study, we investigated the effect of latanoprost on the expression of TGF- ß1 and Wnt / ß - Catenin signal pathway in the choroid of form-deprivation myopia model rats. Forty rats were randomly divided into two groups: the control group and the FDM model group. Each group had 20 rats. The FDM model group was established by feeding latanoprost daily for 28 days. 15 rats in each group were used to measure the length of the ocular axis and the level of TGF-ß1 in choroidal tissue; the remaining 5 rats in each group were used for choroidal fibroblast culture. After modeling, the rats were killed, the length of the ocular axis was measured with a vernier caliper, and the level of TGF - ß1 protein and mRNA in the choroidal tissue of each group were measured with RT-PCR method. Results showed that compared with the control group, there was a significant difference in the axial length of the FDM model group (P< 0.05). There was a significant difference in the expression of TGF- ß1 protein and mRNA between the two groups (P<0.05). The cultured cells were identified as choroidal fibroblasts by immunocytochemistry. There was no significant difference (P>0.05) in the comparison of GSK3 ß protein in choroidal fibroblasts of rats in each group. TGF-ß 1 and APC protein in FDM group were significantly lower than those in the control group (P<0.05), while dcl3, p21-gsk3 ß and ß - Catenin proteins were significantly higher (P<0.05), and there was no significant difference (P>0.05) in the ratio of various indexes protein in FDM + ddk1 group and the comparison of TGF - ß1 and APC protein in FDM + ddk1 group and FDM group The expression of dcl3, p21-gsk3 ß and ß - Catenin decreased significantly (P<0.05). There was no significant difference in the expression of GSK3 ß mRNA in the choroidal fibroblasts of each group (P>0.05). The expression of TGF - ß 1 and APC mRNA in FDM group was significantly lower than that in the control group (P<0.05), while the expression of dcl3, p21-gsk3 ß and ß-catenin mRNA in FDM + ddk1 group was significantly higher than that in the control group (P<0.05) >In FDM + ddk1 group, TGF-ß 1 and APC mRNA were significantly lower than those in FDM group (P<0.05), while dcl3, p21-gsk3 ß and ß-Catenin mRNA were significantly higher (P<0.05).

[Absorption mechanism of dragon's blood phenolic extracts in Caco-2 cells].

The purpose of this study was to study the absorption characteristics of eight main components from dragon's blood phenolic extracts in Caco-2 cells based on the humancolon cancer cell Caco-2 model, and to clarify the oral absorption mechanism of such phenolic extracts. UPLC-MS/MS was used in this study to determine the content of 8 active ingredients including thevetiaflavone, 7,4'-dihydroxyflavone, 7,4'-dihydroxy-5-methoxyhomoisoflavanone, 7,4'-dihydroxyhomoisoflavanone, loureirin C, loureirin A, loureirin B and pterostilbene from dragon's blood phenolic extracts, and Caco-2 cells were used to investigate the effects of incubation time, concentration, temperature, P-gp inhibitor, MRP inhibitor, OCTN1 inhibitor and OCTN2 inhibitor on the absorption of each component. In addition, the transport experiment was conducted to measure the apparent permeability coefficient P_(app) and transport rate of the eight main components to predict the oral absorption mechanism of dragon's blood phenolic extracts. The experimental results showed that the cell uptake of the eight main components in dragon's blood phenolic extracts was time-dependent and concentration dependent, and the uptake of each component did not need to consume energy, which was consistent with the passive diffusion process. P-gp inhibitor, MRP inhibitor and OCTN1 inhibitor had no effect on the cell uptake of each component, only the addition of OCTN2 inhibitor significantly reduced the uptake of pterostilbene(P<0.05). In the transport results, the ER values of the outflow rates of the eight components were all less than 1.5. The above results show that the absorption mechanism of the eight components in Draconis resina phenolic extract may be passive diffusion, and pterostilbene may be the substrate of OCTN2.

[Autophagic activity of piperine on small intestine in dementia model mice with Parkinson's disease].

This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of ß-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduced(P<0.05), and the APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). As compared with the 3 MA group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in the low and medium dose piperine groups and rapamycin group(P<0.05); howe-ver, their first foot licking time was significantly prolonged, APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were increased significantly(P<0.05). As compared with the medopar group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in low dose piperine group and rapamycin group(P<0.05), but their first foot licking time was significantly extended, and APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). In addition, as compared with the normal group, the small intestinal epithelial cells of the model group and the rapamycin group were shed off a lot, with severe damages of intestinal mucosa as well as edema and shedding of the small intestine villi. After administration of the therapeutic interventions, the small intestinal epithelial cells of the 3 MA group, each dose group of piperine, and the medopa group were slightly damaged and the villi were slightly shed off. In summary, piperine has a protective effect on the small intestine of PDD model mice, showing reduced expression of mmu-miR-99 a-5 p, pro-inflammatory factors and autophagy factors, and the mechanism of slowing PDD pathological symptoms may be related to the inhibition of autophagy.

[Study on quality standard of fried Vaccariae Semen standard decoction].

According to the preparation principle of standard decoction of Chinese herbal medicines, fourteen batches of fried Vaccariae Semen decoction were prepared in this study and the quality research was carried out to establish a quality evaluation method for the standard decoction of fried Vaccariae Semen. The contents of vaccarin were determined, and its transfer rate from decoction piece to standard decoction was calculated. The extract rate and pH value were measured, and HPLC fingerprint method was established for analysis. The results of the 14 batches of samples revealed that the transfer rates of vaccarin were between 58.98%-93.94%; the extract rates were between 8.67%-17.83%, and the pH values were between 5.55-6.44. Moreover, 9 common chromatographic peaks were identified in fingerprints analysis. The similarities of the 14 batches of samples were analyzed and compared, and the results showed that the similarities were all higher than 0.96. In this study, the preparation process for fried Vaccariae Semen standard decoction was standard, with high similarities in fingerprint. A convenient and reliable method of comprehensive quality evaluation was established in this study, with a high precision, stability and repeatability, which can provide a reference for the quality control of fried Vaccariae Semen standard decoction, dispensing granule and related Chinese classical formulas(decoction).

[Recommendations on quality standards of Andrographis Herba and its processed slices in Chinese Pharmacopoeia (2020 edition)].

To improve and perfect the quality standards and propose recommendations for the revision of quality standards for Andrographis Herba and its processed slices in Chinese Pharmacopoeia(ChP)(2020 edition) based on the problems and limitations in ChP(2015 edition). TLC identification method with andrographolide and control herbs as references was established using silica gel G thin layer plate, with chloroform-methylbenzene-methanol(8∶1∶1) as developing solvent, and 10% sulfuric acid ethanol solution as colour-developing agent. This method has good reproducibility, strong specificity and high sensitivity. As compared with the original method in ChP 2015, this method has better development effect and clearer spots. Based on the previous research, a quantitative analysis of multi-components by single-marker(QAMS) method with andrographolide as the internal reference substance was developed to simultaneously determine the contents of 4 diterpene lactones: andrographolide(S), neoandrographolide(A), 14-deoxyandrographolide(B), and dehydroandrographolide(C). The relative correction factors of f_(A/S), f_(B/S), and f_(C/S) were determined as 1.12, 0.79, and 0.63, respectively. The relative retention time of t_(A/S), t_(B/S), and t_(C/S) was 1.95, 2.18, and 2.25, respectively. According to the content determination results in 46 batches of crude drugs and 38 batches of processed slices, it was stipulated that the total contents of 4 diterpene lactones should not be less than 1.5% and 1.2% in crude drugs and processed slices, respectively. As compared with the original method in ChP 2015, the present QAMS method could not only reduce the detection cost and improve the efficiency, but also can be used to evaluate the quality of Andrographis Herba and its processed slices more comprehensively and objectively. Diterpene lactones are generally recognized as the effective components in Andrographis Herba, and their contents in leaves were much higher than those in stems. However, almost all of the current commercial processed slices are processed from stems, so their quality is gene-rally poor and the efficacy is hard to be guaranteed. Therefore, the weight percentage of leaves should be added into the inspection items of the processed slices and it should not be less than 25%.

Predictive Value of Head-Neck CTA Combined with ABCD2 Scale Score for Patients with Cerebral Infarction of Vertebrobasilar Transient Ischemic Attack (TIA).

BACKGROUND The present study was designed to evaluate the predictive value of head-neck computed tomography angiography (CTA) combined with ABCD2 score scale for patients with cerebral infarction of vertebrobasilar transient ischemic attack (TIA). MATERIAL AND METHODS A total of 92 patients with TIA who were admitted to our hospital from January 2014 to June 2015 were enrolled in this study. ABCD2 score and CTA combined with ABCD2 score were assessed. RESULTS The incidence of cerebral infarction was highest in the high-risk group, followed by the middle-risk group and low-risk group. The incidence of cerebral infarction was related to the degree of stenosis in head-neck CTA, which was highest in the severe stenosis group, followed by the moderate stenosis group and mild stenosis/normal group, with significant differences. The incidence of cerebral infarction in patients with cerebral artery stenosis was correlated with the incidence of cerebral infarction in the head and neck CTA, which was severe > medium > normal/low (P<0.05). CONCLUSIONS The ABCD2 score can accurately predict the early development from TIA to cerebral infarction. If it is used in combination with head-neck CTA; CTA combined ABCD2 score can further improve the accuracy of prediction, which makes it feasible for use in prediction of the development of vertebrobasilar TIA to cerebral infarction.

Etiology and Clinical Characteristics of Community-Acquired Pneumonia with Airway Malacia in Children.

Objective: The objective of this article is to study the etiology of community-acquired pneumonia in children with airway malacia. Methods: We retrospectively reviewed the medical records of 428 pneumonia patients. All patients underwent bronchoscopy, and bronchoalveolar lavage samples were processed for microbiological assessment. Results: In a total of 428 cases reviewed, 60 were found to have airway malacia. Pathogens were identified in 44 of the 60 specimens (73.3%), with 32 being single-pathogen infections. The most common pathogen was respiratory syncytial virus (RSV; 20%). Mixed-pathogen infections were observed in 12 patients. Airway malacia patients were younger than those without malacia (10.5 vs. 50 months, respectively; p < 0.001). Compared with those without airway malacia, wheezing, cyanosis and admission to the pediatric intensive care unit were more common in children with airway malacia and their hospital stay was longer. Conclusion: RSV was the most common pathogen in those with airway malacia. Airway malacia was found to aggravate infectious pneumonia.

Exome sequencing identifies POU4F3 as the causative gene for a large Chinese family with non-syndromic hearing loss.

Hearing impairment, or deafness (in its most severe form), is one of the most common human sensory disorders. There have been several reports of autosomal dominant mutations in the POU4F3 gene, which is associated with non-syndromic hearing loss. In this study, we identified a novel heterozygous mutation (c.602delT, p.L201fs) in the gene POU4F3 by taking advantage of whole-exome sequencing, which was validated by Sanger sequencing and completely co-segregated within a large hearing impaired Chinese family. We have focused on this pedigree since 2002, and we have mapped a deafness locus named DFNA42 (which has been renamed DFNA52, OMIM entry 607683) via a genome-wide scan. Furthermore, we analyzed this mutational variant and found that it was located at the beginning of the first functional domain of POU4F3, which could theoretically impair the function of POU4F3. We have identified a novel frameshift mutation in the POU4F3 gene. Further functional studies of variants of this specific gene are needed to illustrate the pathogenic mechanism(s) that underlie hearing impairment.

Evaluation of the impact of a chronic disease scheme reimbursing medical costs of patients with diabetes in Anhui province, China: a follow-up study.

BACKGROUND: Although many studies have investigated the relationship between the introduction of the New Cooperative Medical Scheme (NCMS) in rural China in 2003 and increased use of medical services, the effect on health status, objectively measured, is seldom reported. In Anhui Province a chronic disease scheme (CDS) for reimbursing part of the cost of outpatient care is designed to improve management of those with chronic conditions, including diabetes. METHODS: A follow-up study was designed in which patients with diabetes aged 40-70 years who had recently (in 2010) been granted a chronic disease card were individually matched on age, sex and village with a patient with diabetes not yet in the scheme. Each subject gave a fingertip sample of blood to give the concentration of glycosylated hemoglobin (HbA1c), a measure indicating blood glucose control during the previous 3 months. This measure was made on recruitment and at 12 month follow-up: information on use of health services, quality of life and financial burden was also collected at the two contacts. RESULTS: Of 602 pairs initially recruited, 528 pairs were contacted at follow-up and are the subject of this report. To distinguish between outcomes associated with application and those of membership of the scheme, the primary analysis was of 256 pairs in which one had been a member of the CDS throughout and the other never applied. No difference between pairs on HbA1c was found either at recruitment or follow-up but those in the CDS reported more hospital visits, more tests and more use of high level hospitals. However they had poorer scores on quality of life scales (SF-12, EQ-5D) and were more likely to report that the financial costs were very burdensome. Those recently applying for the scheme, or being accepted since recruitment, had lower HbA1c scores. CONCLUSIONS: On-going membership of the CDS was associated with increased use of services but this did not appear to result in better management of blood glucose or improved quality of life. Those who had recently joined the scheme had signs of improvement, suggesting a need for active follow-up to maintain and reinforce early gains.

iTRAQ-Based Quantitative Proteomic Analysis of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a common disease in the southern provinces of China with a poor prognosis. To better understand the pathogenesis of NPC and identify proteins involved in NPC carcinogenesis, we applied iTRAQ coupled with two-dimensional LC-MS/MS to compare the proteome profiles of NPC tissues and the adjacent non-tumor tissues. We identified 54 proteins with differential expression in NPC and the adjacent non-tumor tissues. The differentially expressed proteins were further determined by RT-PCR and Western blot analysis. In addition, the up-regulation of HSPB1, NPM1 and NCL were determined by immunohistochemistry using tissue microarray. Functionally, we found that siRNA mediated knockdown of NPM1 inhibited the migration and invasion of human NPC CNE1 cell line. In summary, this is the first study on proteome analysis of NPC tissues using an iTRAQ method, and we identified many new differentially expressed proteins which are potential targets for the diagnosis and therapy of NPC.