[Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene].

Objective: The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. Methods: The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (ß3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and ß3 in platelets were analyzed by Western blot. Results: Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and ß3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the ß-propeller domain of the p.S160-S192 deletion lost two ß-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a ß chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of ß3 was 11.36% of the normal level. Conclusion: The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

[CT texture analysis for predicting pseudoprogression in metastatic clear cell renal cell carcinoma during PD-1 inhibitor therapy].

Objective: To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy. Methods: A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis. Results: A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included"original_ngtdm_Strength"(0.49 vs. -0.61,P=0.006), "wavelet-HLH_glszm_ZonePercentage"(0.67 vs. -0.22,P=0.024),"wavelet-LHL_ngtdm_Strength"(1.20 vs. -0.51,P=0.002), "wavelet-HLL_gldm_LargeDependenceEmphasis"(-0.84 vs. 0.19,P=0.002), "wavelet-HLH_glcm_Id" (-0.30 vs. 0.43,P=0.037),"wavelet- HLH_glrlm_RunPercentage"(0.45 vs. -0.01,P=0.032),"wavelet-LHH_firstorder_Skewness"(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95%CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95%CI 0.817-0.997) according to ROC curve analysis. Conclusions: Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.

[Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma].

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

[Effects and mechanism of sodium hydrosulfide on rat epidermal cells intervened with serum from burned rat].

Objective: To investigate the effects and mechanism of sodium hydrosulfide on rat epidermal cells intervened with serum from burned rat (hereinafter referred to as burn serum). Methods: The experimental research method was used. Ten male Sprague-Dawley (SD) rats aged eight months were taken to prepare normal rat serum (hereinafter referred to as normal serum), 30 male SD rats aged eight months were taken to prepare burn serum after full-thickness burn, and epidermal cells (the third passage)isolated from 10 SD rats born one day were used for the experiments. The cells were divided into normal serum group treated with normal serum and burn serum group treated with burn serum. Cell counting kit 8 method was used to detect cell survival rate after 1, 2, 4, 6, and 8 h of culture, respectively, to screen the subsequent intervention time of burn serum. The cells were divided into burn serum control group treated only with burn serum and 50, 100, 150, 200, 250 µmol/L sodium hydrosulfide groups treated with burn serum+ sodium hydrosulfide at corresponding final molarity. After 30 min of culture following the burn serum intervention, the cell survival rate was detected as above to screen the subsequent intervention concentration of sodium hydrosulfide. The cells were divided into burn serum control group treated with burn serum only and sodium hydrosulfide only group, glibenclamide only group, and sodium hydrosulfide+ glibenclamide group treated with burn serum+ corresponding reagents. After 5, 10, 15 min of culture following the burn serum intervention, the cell survival rate was detected as above to screen the subsequent intervention time of glibenclamide. The cells were divided into burn serum control group treated with burn serum and sodium hydrosulfide only group, glibenclamide only group, and sodium hydrosulfide+ glibenclamide group treated with burn serum+ corresponding reagents. After completing corresponding culture time of each reagent, the mitochondria were extracted to detect cytochrome c oxidase (CCO) activity using a spectrophotometer, and the protein expression level of adenosine triphosphate (ATP)-sensitive potassium channel was detected by Western blotting. Except for the number of samples for ATP-sensitive potassium channel protein detection, which was 3, the number of samples for the other indicators was 10. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, least significant difference (LSD)-t test, LSD test, and Bonferroni correction. Results: Compared with that of normal serum group, the cell survival rate was significantly decreased in burn serum group after only 4 and 6 h of culture (t=4.02, 6.42, P<0.05). An overall comparison showed statistically significant differences in cell survival rate among the time points within normal serum group and burn serum group (F=19.74, 4.48, P<0.05 or P<0.01). Four hours of culture was selected as the subsequent intervention time of burn serum. After 30 min of culture following the burn serum intervention, compared with that of burn serum control group, only 150, 200, 250 µmol/L sodium hydrosulfide groups had a significantly higher cell survival rate (P<0.01), thus 150 µmol/L was selected as the subsequent intervention concentration of sodium hydrosulfide. Compared with that of burn serum control group, the cell survival rate decreased significantly in glibenclamide only group after 5 and 15 min of culture following burn serum intervention (P<0.05) and increased significantly in glibenclamide only group after 10 min of culture following the burn serum intervention and sodium hydrosulfide only group at each time point (P<0.05 or P<0.01). The cell survival rate in sodium hydrosulfide+ glibenclamide group was significantly lower than that of sodium hydrosulfide only group at each time point (P<0.05). The difference in cell survival rate was statistically significant among the time points within glibenclamide only group (F=11.81, P<0.01). Five minutes of culture was selected as the subsequent intervention time of glibenclamide. After 35 min of culture following the burn serum intervention, compared with (1.62±0.08) nmol·min(-1)·mg(-1) and 0.682±0.063 in burn serum control group, the CCO activity of cells and the protein expression level of ATP-sensitive potassium channel were significantly increased in sodium hydrosulfide only group ((1.99±0.09) nmol·min(-1)·mg(-1) and 0.932±0.014, P<0.01) and significantly decreased in glibenclamide only group ((1.44±0.09) nmol·min(-1)·mg(-1) and 0.600±0.012, P<0.01); the CCO activity of cells and the protein expression level of ATP-sensitive potassium channel in sodium hydrosulfide+ glibenclamide group ((1.79±0.06) nmol·min(-1)·mg(-1) and 0.744±0.071) was significantly lower than those of sodium hydrosulfide only group (P<0.05 or P<0.01). Conclusions: Sodium hydrosulfide can improve the survival rate of rat epidermal cells after burn serum intervention, by a mechanism which is related to the alleviation of epidermal cell mitochondrial damage and mediated by ATP-sensitive potassium channel.

Pressure-induced enhancement of thermoelectric power factor in pristine and hole-doped SnSe crystals.

We evaluate the influence of pressure on the thermoelectric power factors PF ≡ S 2 σ of pristine and Na-doped SnSe crystals by measuring their electrical conductivity σ(T) and Seebeck coefficient S(T) up to ∼22 kbar with a self-clamped piston-cylinder cell. For both cases, σ(T) is enhanced while S(T) reduced with increasing pressure as expected, but their imbalanced variations lead to a monotonic enhancement of PF under pressure. For pristine SnSe, σ(290 K) increases by ∼4 times from ∼10.1 to 38 S cm-1, while S(290 K) decreases by only ∼12% from 474 to 415 µV K-1, leading to about three-fold enhancement of PF from 2.24 to 6.61 µW cm-1 K-2, which is very close to the optimal value of SnSe above the structural transition at ∼800 K at ambient pressure. In comparison, the PF of Na-doped SnSe at 290 K is enhanced moderately by ∼30% up to 20 kbar. In contrast, the PF of isostructural black phosphorus with a simple band structure was found to decrease under pressure. The comparison with black phosphorus indicates that the multi-valley valence band structure of SnSe is beneficial for the enhancement of PF by retaining a large Seebeck coefficient under pressure. Our results also provide experimental confirmation on the previous theoretical prediction that high pressure can be used to optimize the thermoelectric efficiency of SnSe.

[Classification of sudden deafness prognosis based on deep learning method].

Objective:This study aimed to develop predictive models for sudden sensorineural hearing loss through deep belief network (DBN) and explore whether the model performances differ when adopting different outcome criteria. Method: 228 potential predictors involving the clinical characteristics, audio logical data, and serological parameters out of 1 220 hospitalized SSHL patients who were admitted from June 2008 to December 2015 were analyzed retrospectively. The hearing data of sudden deafness were classified into two or four categories based on Chinese criteria and Siegel criteria, which were used to develop the DBN models. The area under the receiver operating characteristic curve (ROC-AUC) and accuracy were used to compare the predictive performance of different models. Result: The DBN model developed for predicting the dichotomized outcomes had better performance than that of the fourcategory outcomes. When the iteration number reached 500 times, DBN model constructed for prediction of dichotomized outcomes based on Siegel's criteria had demonstrated the best performance with an accuracy of 76.25% and an AUC of 0.81. According to indices from first layer weights, DBN gave a rank of top 10 sensitive features for hearing outcome prediction focusing on indicators regarding coagulation, demographics and pre-treatment hearing levels independent of the outcome assessment criteria. Conclusion: DBN provides a robust outcome prediction ability in SSHL datasets with rich and complex variables, especially when utilized to predict dichotomized outcomes based on the Siegel criteria. In addition, this advanced deep learning technique can automatically extract valuable predictors, which is consistent with those that had been verified in previous studies by traditional statistical methods. This study provides further evidence for extending the use of DBN algorithm to the field of developing prediction or classification models for other otological diseases in the future..

Retinal vasculopathy in patients with systemic lupus erythematosus.

A retrospective case control study was conducted in the Peking Union Medical College Hospital. Medical records were reviewed for demographic data, clinical features, laboratory results, systemic lupus erythematosus (SLE) disease activity evaluations, and ophthalmic examinations to investigate the clinical characteristics and significance of retinal vasculopathy (RV) in Chinese patients with systemic lupus erythematosus. The prevalence of RV was approximately 0.66% (35/5298) in SLE patients. A total of 60 eyes were involved. The ocular presentations included decrease of visual acuity (48/60, 80%), visual field loss (7/60, 11.7%), and diplopia (3/60, 5%). Ophthalmic fundoscopic examination revealed cotton-wool spots (30/60, 50%), retinal vascular attenuation (31/60, 51.6%), and hemorrhages (41/60, 68.3%). Retinal angiogram showed that 72.7% (16/22) eyes had vaso-occlusion. The ophthalmic episodes could occur at any stage of SLE duration, with a median of 12 months (0-168 months) following SLE onset. Twenty-one (35%) eyes did not recover, or even worsened, during hospital stay. RV was found to be significantly associated with neuropsychiatric lesions (51.4% vs. 21.3%, p = .005) and hematological disturbance (62.9% vs. 34.3%, p = .005). SLE patients with RV had significantly higher SLE disease activity index scores than controls (19.9 ± 0.9 vs. 10.2 ± 0.7, p < .001). An inverse association of anti-SSA antibody with RV was detected (34.3% vs. 67.1%, p = .001). Nervous system disturbance (odds ratio (OR) = 4.340, 95% confidence interval (CI) 1.438, 13.094, p = .009) and leukocytopenia (OR = 6.385, 95% CI 1.916, 21.278, p = .003) were independent risk factors, while anti-SSA antibody positivity (OR = 0.249, 95% CI 0.087, 0.710, p = .009) was a protective factor for RV in SLE patients. In certain cases, RV is a threatening condition for SLE patients presenting with clinical ocular manifestations. Ophthalmo-fundoscopic detection is recommended as soon as SLE is diagnosed.

[Effect of serum interleukin-21 on B cell secretory capacity and apoptosis in patients with systemic lupus erythematosus].

Objective: To investigate the secretory capacity and apoptosis of interleukin (IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE). Methods: Serum from twenty new-onset SLE patients and 20 healthy donors were collected. CD(19)(+) B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 µg/ml). Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5. Supernatant anti-dsDNA level was determined by ELISA. The percentage of apoptotic cells was detected by flow cytometer. Results: IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum were significantly higher than those in the serum of SLE patients alone [(5.84±1.79)g/L vs (4.25±1.48)g/L, P=0.000; (0.46±0.21)g/L vs (0.43±0.21)g/L, P=0.003; (127.76±70.24)IU/ml vs (115.15±63.88) IU/ml, P=0.014 respectively]. However, no significant differences were found in the group of normal B cells with non-homologous serum from normal controls (P>0.05). Supernatant IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum significantly decreased while IL-21R-fusion protein was added [(5.26±1.62)g/L vs (5.84±1.79)g/L, P=0.006; (0.42±0.20)g/L vs (0.46±0.21)g/L, P=0.002; (118.00±69.62)IU/ml vs (127.76±70.24)IU/ml, P=0.012 respectively]. The apoptotic rate of B cells with SLE serum was significantly higher than that with normal serum [(47.88±12.65)% vs (38.86±10.32)%, P=0.004]. But adding IL-21R-fusion conversed the apoptotic rates [(42.08±12.52)% vs (47.88±12.65)%, P=0.001]. Conclusions: SLE serum could induce normal B cells to form immunoglobulin secreting cells and producing autoantibodies, or apoptosis in pathological conditions. IL-21 might be considered as a potential therapeutic target of SLE.

[Platelet to lymphocyte ratio in peripheral blood and body mass index: novel independent prognostic factors in patients with melanoma].

Objective: To investigate whether platelet to lymphocyte ratio (PLR) in peripheral blood and body mass index (BMI) can be independent prognostic factors in patients with melanoma. Methods: Clinical date of 140 patients with melanoma in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from January 1, 2010 to December 31, 2015 were analyzed retrospectively.Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR.The 140 patients were divided into high PLR group and low PLR group.According to "Guidelines for prevention and control of overweight and obesity in Chinese adults" , the patients were divided into high BMI group and low BMI group.The relationship between PLR, BMI with overall survival (OS), progression free survival (PFS) and disease free survival (DFS) were analyzed.The Kaplan-Meier method and Log rank test was used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. Results: The optimal cut-off value of PLR determined by ROC curve was PLR=120.15, and BMI threshold was 24.Univariate survival analysis showed that PLR, BMI and clinical stage were the factors affecting the OS in patients (P<0.05). The median survival time (MST) was 21 months in the whole group and 17 months in the high PLR group, 34 months in the low PLR group, respectively; the MST in the high and low BMI group were 29 months and 13 months, respectively.The difference was statistically significant (P<0.05). The effects of PLR and BMI on PFS and DFS were not statistically significant.Cox multivariate analysis showed that PLR, BMI and clinical stage were independent prognostic factors of OS (P<0.05). And BMI was the only independent protective factor for OS, the risk of death decreased by 0.611 times, with each unit increased for BMI.Clinical subgroup analysis showed that PLR also was risk factor to the prognosis of patients with stage Ⅱ, Ⅲ, and Ⅳ (P<0.05). Conclusions: PLR is an independent prognostic risk factor for patients with melanoma, and BMI is an independent protective factor.PLR and BMI are important factors in prognostic evaluation of melanoma.

[Cerebral infarction in a patient with primary Sjogren's syndrome: a case report and literature review].

Sjogren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytes infiltration in the exocrine glands. Central nervous system complications of primary SS are not rare, but ischemic stroke has been rarely reported. Here we report a 43-year-old female with a two-year history of primary SS, presenting with sudden cerebral infarction. Her primary SS was diagnosed on the basis of clinical features, high levels of serum anti-SSA and anti-SSB antibodies, salivary gland secretion evaluation and positive sublingual gland biopsy results. Magnetic resonance imaging revealed infarct lesions in the parietal and occipital lobes, as well as in the left basal ganglia. Magnetic resonance angiography showed a remarkable stenosis in the left middle cerebral artery. Other differential diagnoses were ruled out. Corticosteroid and immunosuppressor, together with anti-platelet and statin were effective, and the patient recovered quickly without sequelae. Based on these findings, vasculitis due to primary SS should be considered among the causes of stroke. The literature was reviewed and the relationship between primary SS and cerebral infarction explored. The pathogenesis of ischemic stroke in primary SS is still unknown and warrants further studies.

PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Roles for insulin-supported skeletal muscle growth.

Basic principles governing skeletal muscle growth and development, from a cellular point of view, have been realized for several decades. Skeletal muscle is marked by the capacity for rapid hypertrophy and increases in protein content. Ultimately, skeletal muscle growth is controlled by 2 basic means: 1) myonuclear accumulation stemming from satellite cell (myoblast) proliferation and 2) the balance of protein synthesis and degradation. Each process underlies the rapid changes in lean tissue accretion evident during fetal and neonatal growth and is particularly sensitive to nutritional manipulation. Although multiple signals converge to alter skeletal muscle mass, postprandial changes in the anabolic hormone insulin link feed intake with enhanced rates of protein synthesis in the neonate. Indeed, a consequence of insulin-deficient states such as malnutrition is reduced myoblast activity and a net loss of body protein. A well-characterized mechanism mediating the anabolic effect of insulin involves the phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling pathway. Activation of mTOR leads to translation initiation control via the phosphorylation of downstream targets. Modulation of this pathway by insulin, as well as by other hormones and nutrients, accounts for enhanced protein synthesis leading to efficient lean tissue accretion and rapid skeletal muscle gain in the growing animal. Dysfunctional insulin activity during fetal and neonatal stages likely alters growth through cellular and protein synthetic capacities.

Skeletal muscle and hepatic insulin signaling is maintained in heat-stressed lactating Holstein cows.

Multiparous cows (n=12; parity=2; 136±8 d in milk, 560±32kg of body weight) housed in climate-controlled chambers were fed a total mixed ration (TMR) consisting primarily of alfalfa hay and steam-flaked corn. During the first experimental period (P1), all 12 cows were housed in thermoneutral conditions (18°C, 20% humidity) with ad libitum intake for 9 d. During the second experimental period (P2), half of the cows were fed for ad libitum intake and subjected to heat-stress conditions [WFHS, n=6; cyclical temperature 31.1 to 38.9°C, 20% humidity: minimum temperature humidity index (THI)=73, maximum THI=80.5], and half of the cows were pair-fed to match the intake of WFHS cows in thermal neutral conditions (TNPF, n=6) for 9 d. Rectal temperature and respiration rate were measured thrice daily at 0430, 1200, and 1630 h. To evaluate muscle and liver insulin responsiveness, biopsies were obtained immediately before and after an insulin tolerance test on the last day of each period. Insulin receptor (IR), insulin receptor substrate 1 (IRS-1), AKT/protein kinase B (AKT), and phosphorylated AKT (p-AKT) were measured by Western blot analyses for both tissues. During P2, WFHS increased rectal temperature and respiration rate by 1.48°C and 2.4-fold, respectively. Heat stress reduced dry matter intake by 8kg/d and, by design, TNPF cows had similar intake reductions. Milk yield was decreased similarly (30%) in WFHS and TNPF cows, and both groups entered into a similar (-4.5 Mcal/d) calculated negative energy balance during P2. Insulin infusion caused a less rapid glucose disposal in P2 compared with P1, but glucose clearance did not differ between environments in P2. In liver, insulin increased p-AKT protein content in each period. Phosphorylation ratio of AKT increased 120% in each period after insulin infusion. In skeletal muscle, protein abundance of the IR, IRS, and AKT remained stable between periods and environment. Insulin increased skeletal muscle p-AKT in each period, but the phosphorylation ratio (abundance of phosphorylated protein:abundance of total protein) of AKT was decreased in P2 for TNPF animals, but not during WFHS. These results indicate that mild systemic insulin resistance during HS may be related to reduced nutrient intake but skeletal muscle and liver insulin signaling remains unchanged.

[Characteristics of tinnitus related to idiopathic suddensensorineural hearing loss in 272 patients].

Objective:To investigate the characteristics of sudden sensorineural hearing loss (SSHL) patients with tinnitus.Method:Two-hundred and seventy two SSHL patients with tinnitus underwent evalution through Tinnitus Handicap Inventory(THI) and Tinnitus Questionnaire(TQ).Demographic data and tinnitus characteristics were analyzed.Result:In 272 patients,41.6% of patients suffered from low frequency tinnitus,2.0% with medium frequency tinnitus,56.4% with high frequency tinnitus.There were 79% patients whose tinnitus were continous,while 21% were intermittent;From the view point of daily life compromising,37.4% were minor,44.8% were moderate,17.8% were serious.The most important factors that deteriorate tinnitus were bad sleep,noise,life pressure and tiredness.Conclusion:There were individual differences among patients with sudden deafness and tinnitus.Enough evaluation should be made to decrease the infection of tinnitus.

Broad temperature plateau for thermoelectric figure of merit ZT>2 in phase-separated PbTe0.7S0.3.

Thermoelectrics interconvert heat to electricity and are of great interest in waste heat recovery, solid-state cooling and so on. The efficiency of thermoelectric materials depends directly on the average ZT (dimensionless figure of merit) over a certain temperature range, which historically has been challenging to increase. Here we report that 2.5% K-doped PbTe0.7S0.3 achieves a ZT of >2 for a very wide temperature range from 673 to 923 K and has a record high average ZT of 1.56 (corresponding to a theoretical energy conversion efficiency of ~20.7% at the temperature gradient from 300 to 900 K). The PbTe0.7S0.3 composition shows spinodal decomposition with large PbTe-rich and PbS-rich regions where each region exhibits dissimilar types of nanostructures. Such high average ZT is obtained by synergistically optimized electrical- and thermal-transport properties via carrier concentration tuning, band structure engineering and hierarchical architecturing, and highlights a realistic prospect of wide applications of thermoelectrics.

Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

Expressions of BAFF/BAFF receptors and their correlation with disease activity in Chinese SLE patients.

B-cell activating factor belonging to tumour necrosis factor family (BAFF) is essential for B-cell survival and function through interaction with its receptors BAFF receptor 3 (BR3), B-cell maturation antigen (BCMA) and/or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), though BCMA and/or TACI can also bind to a proliferation-inducing ligand (APRIL). We evaluate the correlation of the expressions of these ligands/receptors with different clinical manifestations of systemic lupus erythematosus (SLE). Levels of BAFF and APRIL in plasma from 73 SLE patients were determined by enzyme-linked immunosorbent assay. Expressions of BR3, TACI and BCMA on CD19+ B cells were detected by flow cytometry. Clinical data were collected and disease activity was evaluated using SLEDAI-2000. SLE patients had elevated BAFF and APRIL levels in their plasma. BAFF levels correlated positively with SLEDAI while negatively with the BR3 protein expression on CD19+ B cells (p < .05). The detected BR3 protein expression in SLE patients was reduced on CD19+IgD+CD27-, CD19+IgD+CD27+ as well as CD19+IgD-CD27+ B cells compared to the counterparts of healthy controls (p < .001), whereas SLE patients did not differ from healthy controls in BR3 mRNA levels. In untreated new-onset patients, the expression rate of BR3 on CD19+ B cells correlated negatively with SLEDAI (p < .05). Elevation of BAFF and reduction of BR3 on CD19+ B cells were more obvious in those with lupus nephritis (LN, p < .05). TACI expression on CD19+ B cells was up-regulated only in those subjects with LN (p < .05). Elevated plasma BAFF and reduced BR3 protein expression on peripheral B cells could act as biomarkers for active disease in SLE patients. High expression of TACI may indicate the occurrence of LN.