Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and regulate a wide array of light-dependent physiological processes. Genetic ablation of ipRGCs eliminates circadian photoentrainment and severely disrupts the pupillary light reflex (PLR). Here we show that ipRGCs consist of distinct subpopulations that differentially express the Brn3b transcription factor, and can be functionally distinguished. Brn3b-negative M1 ipRGCs innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, whereas Brn3b-positive ipRGCs innervate all other known brain targets, including the olivary pretectal nucleus. Consistent with these innervation patterns, selective ablation of Brn3b-positive ipRGCs severely disrupts the PLR, but does not impair circadian photoentrainment. Thus, we find that molecularly distinct subpopulations of M1 ipRGCs, which are morphologically and electrophysiologically similar, innervate different brain regions to execute specific light-induced functions.

Association between obesity and sexual maturation in Chinese children: a muticenter study.

OBJECTIVE: We aimed to evaluate the current status of sexual maturation of Chinese children, to examine the association between obesity and early sexual maturation in boys and compare it with girls and to test the hypothesis that the associations differ by gender. STUDY DESIGN: Cross-sectional study. SUBJECTS: A representative sample involving 9812 boys and 8895 girls aged 6-18 years who participated in the Chinese Children and Adolescent Metabolic Syndrome Epidemiologic Study (July 2009- July 2010) were surveyed. METHODS: All subjects had complete anthropometry and sexual maturation data. SUBJECTS who reached Tanner stage 2 or more (5601 boys and 6538 girls) were divided into tertiles based on the timing of sexual maturation. The subjects in the earliest tertile were included into the early-maturing group, and the middle tertile and the latest tertile into the not early-maturing group. Overweight was defined as a body mass index (BMI) ⩾85th percentile and obesity ⩾95th percentile. Logistic regression analysis was used to test how early maturation affected the risk of overweight. Multiple linear regression was used to examine the association between fatness (BMI Z-score) and sexual maturation. RESULTS: Slightly more boys were obese than girls (P<0.01). The median age for girls of the Tanner stage 2 was 9.69 years, and for boys of Tanner stage 2 was 11.25 years. BMI Z-score were higher (P<0.01) in both early-maturing girls and boys, compared with the non-early maturers, respectively. Early sexual maturation was positively associated with obesity in both girls and boys. With covariates adjusted and using non-early maturing as the reference group, odds ratios for combined overweight were 1.48 for boys and 2.64 for girls, and for obesities were 1.61 for boys and 3.49 for girls, respectively. CONCLUSION: Obesity is positively associated with sexual maturation in both boys and girls, and the association does not differ by gender, but the association is stronger in girls than in boys.

[Relationship between body mass index and sexual development in Chinese children].

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

Pubertal development timing in urban Chinese boys.

We describe current pubertal development in healthy urban Chinese boys. A cross-sectional study of the pubertal development of 18,807 urban Chinese boys aged from 3.50 to 18.49years was conducted between 2003 and 2005. Testicular volume was evaluated with a Prader orchidometer. Pubic hair development was assessed according to the Tanner method. Data on spermarche were collected using the status quo method. Probit analysis was used to calculate the median age and 95% CI at different stages of testicular development, pubic hair development and spermarche. By age 9, 12.99% of the boys had a testicular volume of 4mL or greater. The median age of onset of puberty defined as the age at attainment of testicular volume of 4mL or greater was 10.55 (95% CI 10.27-10.79) years. The median age for onset of pubic hair development (PH(2) ) and spermarche was 12.78 (95%CI 12.67-12.89) years and 14.05 (95%CI 13.80-14.32) years, respectively. Pubertal onset in urban Chinese boys is earlier than currently used clinical norms but their pubic hair development occurs relatively late in comparison with the reported data from numerous other countries. There is also evidence of a secular trend towards an earlier age of spermarche since 1979 in Chinese urban boys.

Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy regulation in human hepatocellular carcinoma cells.

It has been shown that drug resistance is extremely common in hepatocellular carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However, the detailed mechanisms remain largely unknown. We have previously shown that endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here, we demonstrated that the unfolded protein response (UPR) inhibits cisplatin-induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR, which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced apoptosis through autophagy regulation. Furthermore, heat-shock protein 27 (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell death through autophagy activation. Taken together, our results indicate that the UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27-mediated autophagy activation.

[Changing prevalence of overweight and obesity among Chinese children aged 6-15 from 2009-2019].

Objective: To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019. Methods: Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants' data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results: Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% (n=1 773) anel 12.5% (n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% (n=2 496) to 19.1% (n=2 781) (χ²=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 (t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% (n=202) and 3.1% (n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% (n=1 233) to 22.8% (n=1 365) significantly (χ²=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 (t=1.426, P<0.01), and the rate of obesity decreased from 9.8% (n=315) to7.9% (n=256) (χ²=6.46, P<0.05), the overweight rate was not stafistically significant (P=0.10), respectively. The obesity rate of boys had risen from 16.4% (n=1 265) to 18.2% (1 407) (χ²=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% (n=1 393) to 20.5% (n=1 579) (χ²=14.26, P<0.01). The overweight+obesity rate rose from 34.4% (n=2 658) to 38.7% (n=2 986) (χ²=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% (n=468) to 5.9% (n=406) (χ²=4.546, P<0.05), the overweight rate rose from 16.0% (n=1 103) to 17.5% (n=1 202) (χ²=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% (n=1 571) to 23.4% (n=1 608) (χ²=0.53, P>0.05). Conclusions: The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.

[Survey of height and weight of children and adolescents at different Tanner stages in urban China].

Objective: To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight. Methods: A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results: The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion: The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.

PI3K/Akt promotes GRP78 accumulation and inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells.

The potential pro-survival role of phosphatidylinositol 3-kinase (PI3K)/Akt during endoplasmic reticulum stress has been well-characterized. However, the detailed mechanisms remain largely unknown. Here, we showed that PI3K/Akt inhibition promoted endoplasmic reticulum stress-induced apoptosis in a glucose-regulated protein 78 (GRP78)-dependent manner. During endoplasmic reticulum stress, high levels of Akt phosphorylation were sustained for at least 18 h in HEK293 cells. Importantly, PI3K/Akt enhanced GRP78 accumulation through increasing its stability following endoplasmic reticulum stress. Furthermore, Akt1, but not Akt2 or Akt3, was involved in GRP78 stability regulation. These results suggest that PI3K/Akt inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells, at least in part, by promoting GRP78 protein stability.

The association of homeobox gene expression with stem cell formation and morphogenesis in cultured Medicago truncatula.

Somatic embryogenesis (SE) is induced in vitro in Medicago truncatula 2HA by auxin and cytokinin but rarely in wild type Jemalong. The putative WUSCHEL (MtWUS), CLAVATA3 (MtCLV3) and the WUSCHEL-related homeobox gene WOX5 (MtWOX5) were investigated in M. truncatula (Mt) and identified by the similarity to Arabidopsis WUS, CLV3 and WOX5 in amino acid sequence, phylogeny and in planta and in vitro expression patterns. MtWUS was induced throughout embryogenic cultures by cytokinin after 24-48 h and maximum expression occurred after 1 week, which coincides with the induction of totipotent stem cells. During this period there was no MtCLV3 expression to suppress MtWUS. MtWUS expression, as illustrated by promoter-GUS studies, subsequently localised to the embryo, and there was then the onset of MtCLV3 expression. This suggests that the expression of the putative MtCLV3 coincides with the WUS-CLAVATA feedback loop becoming operational. RNAi studies showed that MtWUS expression is essential for callus and somatic embryo production. Based on the presence of MtWUS promoter binding sites, MtWUS may be required for the induction of MtSERF1, postulated to have a key role in the signalling required for SE induced in 2HA. MtWOX5 expressed in auxin-induced root primordia and root meristems and appears to be involved in pluripotent stem cell induction. The evidence is discussed that the homeobox genes MtWUS and MtWOX5 are "hijacked" for stem cell induction, which is key to somatic embryo and de novo root induction. In relation to SE, a role for WUS in the signalling involved in induction is discussed.

[Research progress in saliva collection, analysis and its relationship with oral diseases].

As one of the major body fluid, saliva has various components that can shift according to the systemic health state. With the atraumatic way of collection, saliva can be a promising media to help the detection of oral diseases. With the development of salivaomics and the application of unbiased, highly sensitive, and high throughout separation techniques for salivary components, there's now more possibilities for effective identification of biomarkers correlated with oral diseases. This review aimed to introduce the current state of saliva collection and detection techniques as well as their correlation with oral diseases, hoping to provide evidence for further research.

[Analysis of four carnitine-acylcarnitine translocase deficiency cases caused by homozygous mutation of SLC25A20 c.199-10T> G].

Objective: To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases. Methods: Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases. Results: Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 µmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 µmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype. Conclusion: The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.

High frequency of deletion mutations in p53 gene from squamous cell lung cancer patients in Taiwan.

Lung cancer is the leading and second-leading cause of cancer deaths among women and men in Taiwan, respectively. However, the molecular mechanisms involved in lung tumorigenesis in Taiwan remain poorly defined. A study that analyzed the mutation spectrum of the p53 tumor suppressor gene in 35 female lung cancer patients in Hong Kong showed that a high proportion of the mutations observed were deletions, suggesting the possible involvement of a distinct mutagenic factor(s) in Chinese female lung cancer patients (Y. Takagi et al., Cancer Res., 55: 5354-5357, 1995). Therefore, to gain insight into the role of the p53 tumor suppressor gene and possible etiological factors in lung tumorigenesis in Taiwan, we investigated the mutation spectra of exons 4-11 in the p53 tumor suppressor gene of 60 lung cancer patients in Taiwan. These data were also correlated with clinical pathological characteristics of patients. Lung tumors were surgically resected, genomic DNA was isolated, and their mutation spectra were examined using PCR/single-strand conformational polymorphism analysis and direct sequencing. The frequency of p53 gene mutation was 18% (11 of 60). However, distinct patterns of p53 gene mutation were observed. Seven of 11 mutations detected (64%) were deletions of 1-12 bp at G:C bp or at bp in the immediate vicinity of repetitive sequences and/or tandem repeat sequences. In addition, two patients (2 of 11, 18%) exhibited nonsense mutations. In contrast to the frequent occurrence of missense mutations in the p53 gene reported in the literature, the majority (82%) of the mutations in lung cancer patients in Taiwan were nonmissense mutations, ie., deletions and nonsense mutations. Immunohistochemical staining indicated that p53 mutations including non-in-frame deletions and nonsense mutations all resulted in no expression of p53 protein. Notably, mutations occurred more frequently in patients suffering from squamous cell carcinoma (SQ). Nine of 31 SQ patients (29%) exhibited deletions or nonsense mutations, suggesting that deletions and nonsense mutations in the p53 gene are involved in the formation of SQ in Taiwan. In addition, mutations occurred more frequently in patients with stage III or IV lung cancer. However, mutations were not correlated with patients' smoking habits. Our data suggest that p53 gene mutation involved in the formation of SQ and distinct environmental factor(s) and/or genetic factor(s) that induced specific short deletions in repeat sequences may be involved in lung tumorigenesis in Taiwan.

[Genetic analysis for 5 congenital hypothyroidism patients due to dyshormonogenesis].

OBJECTIVE: To analyze molecular characteristics of 5 congenital hypothyroidism (CH) patients due to dyshormonogenesis. METHOD: We enrolled 5 CH patients due to dyshormonogenesis who were identified in Newborn Screening Center of Guangxi Zhuang Autonomous Region, China. Blood samples were collected from the patients and their parents, and genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2, TG, TPO and NIS gene together with their exon-intron boundaries were screened by next-generation sequencing. Specimens from 100 normal controls were tested for these novel variations. RESULT: No TPO, NIS or TG gene mutations were identified. Direct sequencing of the DUOX2 gene revealed that patient 1 had a compound heterozygote for c. 3340delC and p. R683L, patient 2 was homozygous for p. K530X and patient 3 was a heterozygote for p. E879K. Both biallelic and monoallelic heterozygous mutations in DUOX2 were associated with transient CH. Novel mutations included c. 3340delC and p. R683L, analysis of 100 healthy subjects without thyroid disease did not show the same change. CONCLUSION: Genetic analysis of TPO, NIS, DUOX2 and TG gene in 5 unrelated CH patients with thyroid dyshormonogenesis revealed two novel DUOX2 mutations, both were biallelic and monoallelic heterozygous mutations in DUOX2 associated with transient CH.

p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis.

An association between the BstUI (Pro/Pro) genotype of the p53 codon 72 polymorphism and lung cancer has been reported previously (X. Jin et al., Carcinogenesis (Lond.), 16: 2205-2208, 1995). However, the genotype distribution of p53 codon 72 polymorphism as well as the association of this polymorphism with lung cancer risk and prognosis remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of p53 codon 72 polymorphism in 194 lung cancer patients and 152 noncancer controls. The genotype frequencies in Taiwanese noncancer controls were 0.56 (Arg) and 0.44 (Pro). Chi2 analysis indicated significant differences in genotype distribution of p53 from other reports in Swedish (P < 0.001), Spanish (P < 0.001), Caucasians in the United States (P = 0.002), and African-Americans (P = 0.027). In addition, our data suggest that the Pro allele of the p53 codon 72 polymorphism increased the risk of lung cancer among female Taiwanese. The female patients with genotype Pro/Pro showed a significantly increased odds ratio (3.14; confidence interval, 1.48-6.64; P = 0.003) of having lung adenocarcinoma, compared with normal controls with the other genotypes. Patients with the Pro/Pro genotype had an odds ratio of 2.63 (confidence interval, 1.22-5.68; P = 0.01) higher than those with the other genotypes to be diagnosed with lung cancer at the early ages. We further investigated the association of p53 codon 72 polymorphism with prognosis in 133 lung cancer patients. Patients with the Pro/Pro genotype tended to have poorer prognosis than those with the Arg/Pro genotype (P = 0.05, by the log-rank test). Our data suggested that p53 codon 72 polymorphism may play a role in cancer susceptibility and prognosis in specific classes of lung cancer patients in Taiwan.

Correlation of genetic instability with mismatch repair protein expression and p53 mutations in non-small cell lung cancer.

To examine the etiological association of genetic instability in lung tumorigenesis, we investigated the frequency of microsatellite instability (MI) of eight dinucleotide repeat markers in 68 patients with non-small cell lung cancer. Twenty-eight patients (41.2%) evidenced instability in multiple tested microsatellite markers ranging from 3-7 and were defined as MI-positive patients. MI occurred more frequently in patients suffering from squamous cell lung carcinoma (P = 0.004). We examined the association between MI and expression of hMLH1 mismatch repair protein by immunohistochemical analysis of hMLH1 protein in paraffin-embedded tumors from 64 patients. Twenty MI-positive patients (76.9%) had no expression of hMLH1 protein. The data showed that MI was associated with altered hMLH1 expression (P = 0.03). To examine the role of genetic instability in the previous identified small intragenic deletion of the p53 gene, we explored the association between MI and p53 gene mutations. All patients, except one, containing small intragenic deletion in p53 gene showed MI (P = 0.018). In addition, we found that MI was not associated with the prognosis. Our data suggest that MI plays a significant role in non-small cell lung cancer tumorigenesis in Taiwan and that MI is associated with the altered expression of hMLH1 mismatch repair protein. In addition, MI may be involved in frequent small intragenic deletions of p53 gene.

In-vitro Activity of Honey and Topical Silver in Wound Care Management.

BACKGROUND: With the rise of multidrug resistance among pathogens, especially in wound care management is of great concern. Hence, we designed to study the in-vitro activity of topical agents honey and silver against wound infection and compares silver and honey dressings used in wound care. METHODS: 172 isolates from burn and surgical wounds were isolated from patients admitted to Nursing College, Changchun University Of Chinese Medicine, China during 2013-2014 are included in the study. 59 Pseudomonas, 41 E.coli, 28 S aureus, 25 Klebsiella pneumoniae, 11 Proteus, 8 Acinetobacter were isolated. Susceptibility testing for honey and silver nitrate was done using the agar dilution method. 80 patients were divided into 2 groups. Type 1 used Algivon with UMF12 honey coated dressing for 40 patients and the other 40 patients received Type II used Acti-coat silver absorbent dressings. 30 patients received ordinary dressings were included as control group patients. RESULTS: 50/59 (84.7%) Pseudomonas spp, 39 (95.1%) of E.coli and 26/28 (92.9%) S. aureus were sensitive for silver nitrate. K. pneumoniae, Proteus spp and Acinetobacter spp showed 100% sensitivity for silver nitrate by agar dilution method. All the isolates showed 100% sensitivity for honey at concentration. In type I - honey coated dressings consist of 40 patients with 18 (45%) male and 22 (55%) female patients. Type II - silver-coated dressings consist of 40 patients with 24 (60%) females and 16 (40%) male patients. CONCLUSION: This study results showed positive efforts on improvising in wound dressings as a replacement to lower antimicrobial resistance and limit racial use of antibiotics.

Prognostic significance of p53 codon 72 polymorphism in lung carcinomas.

Lung cancer is the leading cause of cancer death in Taiwan. Potential molecular markers associated with cancer susceptibility and prognosis are the genes involved in tumorigenesis. Therefore, we investigated the association of p53 codon 72 polymorphism with prognosis in 114 lung cancer patients. The estimated median survival times for patients with proline (Pro)/Pro, arginine (Arg)/Arg, and Arg/Pro genotypes were 25, 26 and 36 months, respectively. We also found that patients with the Pro/Pro genotype had a worse prognosis compared with those with Arg/Pro genotypes, especially for patients with squamous cell lung cancer (P = 0.013), male patients (P = 0.028) and those aged 60-69 years (P = 0.052). In patients with early stage lung cancer, patients with Pro/Pro and Arg/Arg genotypes had a tendency for a worse prognosis than those with the Arg/Pro genotype (P = 0.057). Our data suggest that p53 codon 72 polymorphism may be a potential prognostic factor in certain sub groups of lung cancer patients in Taiwan.

Analysis of K-ras gene mutations in lung carcinomas: correlation with gender, histological subtypes, and clinical outcome.

PURPOSE: Lung cancer is respectively the leading and second-leading cause of cancer deaths among women and men in Taiwan. The commonest pathological type of lung carcinoma found in Taiwan is adenocarcinoma. and it has been documented that K-ras oncogene mutation occurs in a subset of lung adenocarcinoma. We therefore investigated the mutation spectrum and clinicopathological significance of K-ras oncogene mutations in lung cancer patients in Taiwan. METHODS: The lung tumors were surgically resected from 84 lung cancer patients. DNA was isolated and the mutation spectrum was examined by direct sequencing. These data were also correlated with the clinicopathological characteristics of patients. RESULTS: K-ras gene mutations were detected in 5 cases among the 84 patients investigated (6.0%). The majority of mutations occurred in exon 1 (80%, 4 of 5) and were located mainly in codons 12 and 13. Two patients had G x C --> T x A transversions and 2 patients had G x C --> A x T transitions. Notably, 1 patient had a G x C base-pair deletion from the contiguous G x C base pairs located between codons 68 and 69. All mutations occurred in male patients who were smokers. The incidences of K-ras gene mutation among male and female patients with adenocarcinoma were 13% and 0% respectively. Patients with K-ras gene mutation survived for shorter periods than those without mutations (P = 0.08, by the log-rank test). CONCLUSIONS: The incidence of K-ras gene mutations for male and female patients with adenocarcinoma was 13% and 0% respectively. Thus, the role of K-ras in the development of lung adenocarcinoma among Chinese men who are predominantly smokers is not significantly different from that in other populations worldwide. However, K-ras mutations may not be associated with adenocarcinoma among women in Taiwan, who are virtually all nonsmokers.

Determination of 8-oxoguanine in individual cell nucleus of gamma-irradiated mammalian cells.

8-Oxoguanine, through its ability to mispair bases other than cytosine, is assumed to be one of the most potent premutagenic lesions in nuclear DNA damaged by reactive oxygen radicals. In this study, we examine whether the presence of residual 8-oxoguanine can be detected in mammalian cells after exposure to ionizing radiation. MOLT-4 human leukemia cells and CHO-K1 Chinese hamster cells were acutely irradiated in vitro with 0, 0.2, 0.4, 0.6 and 1.0 Gy gamma radiation at room temperature. The amounts of 8-oxoguanine and total DNA in the cell nucleus were detected by fluorescein-isothiocyanate (FITC)-labeled avidin, which binds specifically and directly to 8-oxoguanine, and propidium iodide, respectively. The intensity ratios between these two fluorescent dyes were then taken as indices to measure the content of 8-oxoguanine within individual cells. We found an apparent dose-dependent increase in the amount of 8-oxoguanine accumulated in cells of both lines. Moreover, the content of 8-oxoguanine decreased from 2 to 20 h after irradiation in CHO-K1 cells, which may reflect the time-dependent repair processes at the 8-oxoguanine lesions. This novel approach may provide a sensitive tool for in situ measurement of 8-oxoguanine in cells or even in the human body after exposure to ionizing radiation.

Evaluation of single-use masks and respirators for protection of health care workers against mycobacterial aerosols.

BACKGROUND: The recent increase in multidrug-resistant tuberculosis has spawned a major controversy concerning the degree of respiratory protection needed by health care workers, particularly during sputum-inducing procedures. The objective of this study was to measure the filtration efficiencies of a single-use submicron surgical mask, two disposable dust/mist respirators, a dust/mist/fume respirator, and a high-efficiency particulate air respirator against aerosolized mycobacteria. Facial fit was not addressed. METHODS: In a specially designed enclosed test apparatus, an aerosol was generated with a Collison nebulizer from a known concentration of Mycobacteria chelonae, used as a surrogate for Mycobacterium tuberculosis. Aerosol concentrations were measured with Anderson samplers upstream and downstream of the test masks and respirators, which were heat sealed to a metal plate. RESULTS: Mean efficiencies ranged from approximately 97% for the surgical mask and a dust/mist respirator to more than 99.99% for the high-efficiency particulate air respirator. Measurements of filter efficiency with an Aerodynamic Particle Sizer for the M. chelonae aerosol and independent challenge tests with latex spheres correlated closely with measurements of M. Chelonae collection efficiency determined with Andersen samplers. CONCLUSIONS: Analysis of variance and Tukey's method for multiple comparisons indicated that the dust/mist/fume respirator and the HEPA respirator collected M. chelonae with significantly greater efficiency than did either the surgical mask or the dust/mist respirator. Even the least efficient mask tested, however, had a filter efficiency of more than 97% against particles averaging less than 1 micron in aerodynamic diameter.