Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents ...use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia.
Sp1, an important transcription factor, is involved in the progression of various cancers. Our previous studies have indicated that Sp1 levels are increased in the early stage of lung cancer ...progression but decrease during the late stage, leading to poor prognosis. In addition, estrogen has been shown to be involved in lung cancer progression. According to previous studies, Sp1 can interact with the estrogen receptor (ER) to coregulate gene expression. The role of interaction between Sp1 and ER in lung cancer progression is still unknown and will be clarified in this study.
The clinical relevance between Sp1 levels and survival rates in young women with lung cancer was studied by immunohistochemistry. We validated the sex dependence of lung cancer progression in EGFR
-induced lung cancer mice. Wound healing assays, chamber assays and sphere formation assays in A549 cells, Taxol-induced drug-resistant A549 (A549-T24) and estradiol (E2)-treated A549 (E2-A549) cells were performed to investigate the roles of Taxol and E2 in lung cancer progression. Luciferase reporter assays, immunoblot and q-PCR were performed to evaluate the interaction between Sp1, microRNAs and CD44. Tail vein-injected xenograft experiments were performed to study lung metastasis. Samples obtained from lung cancer patients were used to study the mRNA level of CD44 by q-PCR and the protein levels of Sp1 and CD44 by immunoblot and immunohistochemistry.
In this study, we found that Sp1 expression was decreased in premenopausal women with late-stage lung cancer, resulting in a poor prognosis. Tumor formation was more substantial in female EGFR
mice than in male mice and ovariectomized female mice, indicating that E2 might be involved in the poor prognosis of lung cancer. We herein report that Sp1 negatively regulates metastasis and cancer stemness in E2-A549 and A549-T24 cells. Furthermore, E2 increases the mRNA and protein levels of RING finger protein 4 (RNF4), which is the E3-ligase of Sp1, and thereby decreases Sp1 levels by promoting Sp1 degradation. Sp1 can be recruited to the promoter of miR-3194-5p, and positively regulate its expression. Furthermore, there was a strong inverse correlation between Sp1 and CD44 levels in clinical lung cancer specimens. Sp1 inhibited CD44 expression by increasing the expression of miR-3194-5p, miR-218-5p, miR-193-5p, miR-182-5p and miR-135-5p, ultimately resulting in lung cancer malignancy.
Premenopausal women with lung cancer and decreased Sp1 levels have a poor prognosis. E2 increases RNF4 expression to repress Sp1 levels in premenopausal women with lung cancer, thus decreasing the expression of several miRNAs that can target CD44 and ultimately leading to cancer malignancy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Previous studies indicate that estrogen positively regulates lung cancer progression. Understanding the reasons will be beneficial for treating women with lung cancer in the future. In this study, we ...found that tumor formation was more significant in female EGFR
mice than in male mice. P53 expression levels were downregulated in the estradiol (E2)-treated lung cancer cells, female mice with EGFR
-induced lung cancer mice, and premenopausal women with lung cancer. E2 increased DNA methyltransferase 1 (DNMT1) expression to enhance methylation in the TP53 promoter, which led to the downregulation of p53. Overexpression of GFP-p53 decreased DNMT1 expression in lung cancer cells. TP53 knockout in mice with EGFR
-induced lung cancer not only changed gene expression in cancer cells but also increased the polarization of M2 macrophages by increasing C-C motif chemokine ligand 5 (CCL5) expression and decreasing growth differentiation factor 15 (GDF15) expression. The TP53 mutation rate was increased in females with late-stage but not early-stage lung cancer compared to males with lung cancer. In conclusion, E2-induced DNMT1 and p53 expression were negatively regulated each other in females with lung cancer, which not only affected cancer cells but also modulated the tumor-associated microenvironment, ultimately leading to a poor prognosis.
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, a small bloodsucking midge, thrives in moderately moist habitats and is commonly found in grassy and bushy areas at an elevation below 250 m. This species exhibits a diurnal biting pattern and ...shows a marked preference for human blood. Although not known to transmit arthropod-borne diseases, the bites of
can induce severe allergic reactions in some individuals. As a significant nuisance in Taiwan, affecting both daily life and the tourism industry, comprehensive studies on its population genetics across different geographical regions remain scarce. The central mountain ranges in Taiwan, comprising more than two hundred peaks above 3000 m in elevation, extend from the north to the south of the island, creating distinct eastern and western geographical divisions. This study utilizes microsatellite markers to explore the genetic differentiation of
populations located in the eastern and western regions of the mountain ranges. Our findings reveal substantial genetic differentiation among populations inhabiting Taiwan's western region compared to those in the eastern region. This indicates that the topographical barriers presented by the mountain ranges significantly restrict gene flow, particularly given the species' limited active flight ability and habitat preferences. Although passive dispersal mechanisms, like wind or human activity, could contribute, this study concludes that the gene flow of
between the western and eastern regions is primarily influenced by topographical constraints.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Hirschsprung's disease (HSCR) is a congenital disorder with the absence of myenteric and submucosal ganglion cells within distal gut. Due to multigenic inheritance and interactions, we ...employed next‐generation sequencing (NGS) to investigate genetic backgrounds of long‐segment HSCR (L‐HSCR) in Taiwan.
Methods
Genomic DNA extracted from peripheral blood of L‐HSCR patients was subjected to capture‐based NGS, based on a 31‐gene panel. The variants with allele frequency <0.05 and predicted by computational methods as deleterious were further validated by Sanger sequencing in patients and their family as well to tell de novo from inherited variants.
Results
Between 2015/04 and 2018/05, this study enrolled 23 L‐HSCR patients, including 15 (65.2%) sporadic cases and 8 (34.8%) familial patients in 4 different families. Six sporadic and seven familial cases showed possible harmful variants across eight different genes, accounting for an overall detection rate of 56.5%. These variants mainly resided in SEMA3C, followed by RET, NRG1, and NTRK1. Three sporadic and 2 familial cases exhibited strong pathogenic variants as a deletional frameshift or stop codon in RET, L1CAM or NRG1. In a HSCR family, the father passed on a pathogenic RET frameshift to two daughters; however, only one developed HSCR.
Conclusion
Using NGS, we disclosed deleterious mutations such as a frameshift or stop codon in either familial or sporadic patients. Our cases with isolated L‐HSCR or even total colonic aganglionosis appeared to exhibit complex patterns of inheritance and incomplete penetrance even in families with the same genetic variants, reflecting the possible effects of environmental factors and genetic modifiers.
Using NGS in this study, we disclosed some definite harmful mutations such as a frameshift or stop codon in either familial or sporadic patients. Our cases with isolated L‐HSCR or even TCA appeared to exhibit complex patterns of inheritance and incomplete penetrance even in families with the same genetic variants, reflecting the possible effects of environmental factors and genetic modifiers.
Exendin-4 is a long acting glucagon-like peptide 1 (GLP-1) analogue that is an agonist for the GLP-1 receptor, a G-protein coupled receptor (GPCR). Exendin-4 is used to clinically improve glucose ...tolerance in diabetic patients due to its ability to enhance insulin secretion. In rodents, and possibly in humans, exendin-4 can stimulate β-cell proliferation. The exact mechanism of action to induce β-cell proliferation is not well understood. Here, using a β-cell specific epidermal growth factor receptor (EGFR) null mouse, we show that exendin-4 induced an increase in proliferation and β-cell mass through EGFR. Thus, our study sheds light on the role of EGFR signaling in the effects of exendin-4 on the control of blood glucose metabolism and β-cell mass.
Drug resistance in cancer therapy is the major reason for poor prognosis. Addressing this clinically unmet issue is important and urgent. In this study, we found that targeting USP24 by the specific ...USP24 inhibitors, USP24-i and its analogues, dramatically activated autophagy in the interphase and mitotic periods of lung cancer cells by inhibiting E2F4 and TRAF6, respectively. USP24 functional knockout, USP24
, or targeting USP24 by USP24-i-101 inhibited drug resistance and activated autophagy in gefitinib-induced drug-resistant mice with doxycycline-induced EGFR
lung cancer, but this effect was abolished after inhibition of autophagy, indicating that targeting USP24-mediated induction of autophagy is required for inhibition of drug resistance. Genomic instability and PD-L1 levels were increased in drug resistant lung cancer cells and were inhibited by USP24-i-101 treatment or knockdown of USP24. In addition, inhibition of autophagy by bafilomycin-A1 significantly abolished the effect of USP24-i-101 on maintaining genomic integrity, decreasing PD-L1 and inhibiting drug resistance acquired in chemotherapy or targeted therapy. In summary, an increase in the expression of USP24 in cancer cells is beneficial for the induction of drug resistance and targeting USP24 by USP24-i-101 optimized from USP24-i inhibits drug resistance acquired during cancer therapy by increasing PD-L1 protein degradation and genomic stability in an autophagy induction-dependent manner.
Hybridization between invasive pest species may lead to significant genetic and economic impacts that require close monitoring. The two most invasive and destructive termite species worldwide, ...Coptotermes formosanus Shiraki and Coptotermes gestroi (Wasmann), have the potential for hybridization in the field. A three-year field survey conducted during the dispersal flight season of Coptotermes in Taiwan identified alates with atypical morphology, which were confirmed as hybrids of the two Coptotermes species using microsatellite and mitochondrial analyses. Out of 27,601 alates collected over three years, 4.4% were confirmed as hybrid alates, and some advanced hybrids (>F1 generations) were identified. The hybrid alates had a dispersal flight season that overlapped with the two parental species 13 out of 15 times. Most of the hybrid alates were females, implying that mating opportunities beyond F1 may primarily be possible through female hybrids. However, the incipient colony growth results from all potential mating combinations suggest that only backcross colonies with hybrid males could sometimes lead to brood development. The observed asymmetrical viability and fertility of hybrid alates may critically reduce the probability of advanced-hybrid colonies being established in the field.
Amyand's hernia (AH) is a rare type of inguinal hernia that occurs when the appendix is trapped within the hernia sac. AH accounts for approximately 1% of all inguinal hernias. However, there is ...currently no comprehensive review on the manifestation of AH in preterm infants.
A male preterm infant, born at 31+5 weeks’ gestational age with a birthweight of 1040 g, presented with a right inguinal mass at 39 days of life. The inguinal mass was firm, irreducible and erythematous. The infant also exhibited symptoms of fever and poor feeding. An abdominal X-ray showed an obstructive ileus consistent with clusters of cyst-like gas bubbles suggesting pneumatosis intestinalis. Recognizing the urgent need for intervention, emergent surgery was performed. A transverse incision along the right inguinal crease. An intraoperative exploration revealed a gangrenous appendix within the hernia which indicating AH. Herniorrhaphy and appendectomy were successfully performed without any postoperative complications. Feeding was resumed 8 days after the surgery, and the infant was discharged soon with full recovery.
AH is characterized by an irreducible inguinal mass that is predominantly found on the right side in preterm infants, especially males. In less mature infants, the manifestation of AH may be more severe. Therefore, AH should be considered in the differential diagnosis of infants with abdominal emergencies, and careful intra-operative assessment is essential. AH typically requires less complex treatment and has a favorable prognosis compared to other abdominal conditions in preterm infants.
Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical ...coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy.
We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA).
Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant.
Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response.
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