Cisplatin combined with gemcitabine, a doublet regimen, is the first-line treatment for patients with advanced lung adenocarcinoma (ADC); however, the treatment response remains poor. This study aimed to identify potential biomarkers for predicting response to cisplatin and gemcitabine. Tissue transcriptome and blood proteome analyses were conducted on 27 patients with lung ADC. Blood-derived proteins that reflected tissue-specific biomarkers were obtained using Venn diagrams. The candidate proteins were validated by Western blotting. Lentivirus-mediated short hairpin RNA interference was used to verify the functional roles of the candidate proteins in human A549 cells. We identified 417 differentially expressed genes, including 52 upregulated and 365 downregulated genes, and 31 differentially expressed proteins, including 26 upregulated and 5 downregulated proteins. Integrative analysis revealed the presence of alpha-1-acid glycoprotein 1 (A1AG1) and fibrinogen alpha chain (FGA or FIBA) in both the tissue and serum. FGA levels were elevated in responders compared to non-responders, and reduced serum FGA levels were correlated with resistance to this regimen. Moreover, FGA knockdown in A549 cells resulted in resistance to the doublet regimen. Our findings indicate that FGA is a tissue-specific serum protein that may function as a blood-based biomarker to predict the response of patients with lung ADC to cisplatin plus gemcitabine chemotherapy.
�Background: Bowen’s disease (BD) is a skin carcinoma in situ occurring over the entire body surface. It shares similar histopathological features with Bowenoid papulosis (BP) of the genitalia, but differs in etiology and clinical course. Increased p16 INK4A (p16) tumor suppressor protein expression has been demonstrated in relation to the progression of cutaneous squamous neoplasms. Objective: To evaluate the difference in p16 expression between Bowen’s disease and Bowenoid papulosis. Material and Method: Biopsies of 46 cases of BD in the period 1994 - 2003 and 14 cases of BP during 1987 - 2003 in the Anatomical Pathology Unit, Department of Pathology, Faculty of Medicine, Prince of Songkla University, Thailand were studied by immunohistochemical methods using the P16 kit (CINTec TM Histology Kit, clone E6H4, Code-Nr. K5334, DakoCytomation, Denmark). Nuclear/cytoplasmic immunoreactivity in more than 10% of neoplastic cells was considered positive. Results: P16 expression was positive in 37 of 46 BD cases (80.4%) which was higher than that of BP (6 of 14 cases or 42.9%) (p value < 0.05, Chi-square test). The expression among the three groups of BD: extragenital (28 of 35), chronic arsenical-related (7 of 8) and genital lesions (2 of 3) was not significantly different (p value = 0.734, Chi-square test). Conclusion: P16 expression was more frequent in BD than BP. This suggests a possible association between p16 expression and tumorigenesis of these lesions.
Carbapenem-resistant Enterobacteriaceae (CRE) is emerging as a major problem in healthcare settings globally, including Thailand, due to limited therapeutic options. We reported the detection, antimicrobial susceptibility profiles, and the presence of carbapenemase genes of CRE isolates obtained from Songklanagarind Hospital between July 2012 and June 2015. A total of 273 non-duplicated CRE isolates was recovered from 248 patients. The predominant organism was Klebsiella pneumoniae (183 [67.0 %]), followed by Escherichia coli (38 [13.9 %]). The susceptibility to 13 antibiotics was performed by disk diffusion assay. Most of the CRE isolates remained susceptible to amikacin. Minimum inhibitory concentrations (MIC) of carbapenems were determined by E-test. The MIC50 and MIC90 were varied among genera and species. Multiplex PCRs for the carbapenemase genes blaIMP, blaVIM, blaOXA-48, blaNDM-1, blaKPC, and blaGES were performed. One hundred and seventy-eight out of these 273 CRE isolates (65.2 %) harbored either single or multiple carbapenemase genes. One hundred and fifty nine isolates harbored the blaNDM-1 gene (113 K. pneumoniae, 25 E. coli, 17 E. cloacae, 2 Citrobacter freundii, 1 Enterobacter aerogenes, and 1 Pantoea agglomerans), 7 isolates carried blaIMP (4 K. pneumoniae, 2 C. freundii, and 1 E. cloacae), 7 isolates possessed blaOXA-48 (1 K. pneumoniae, 5 E. coli, and 1 E. aerogenes), whereas 3 and 2 isolates harbored blaNDM-1 and blaIMP (2 K. pneumoniae and 1 E. cloacae) and blaNDM-1 and blaOXA-48 (1 E. coli and 1 E. cloacae), respectively. In conclusion, this study revealed the detection of CRE, with the majority of K. pneumoniae harboring blaNDM-1 in this setting.
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and it is the leading cause of cancer death globally. Vascular endothelial growth factor (VEGF) plays an important role in cancer progression, including lung cancer. Therefore, it would be interesting to determine key modulators that can suppress VEGF production. This study aimed to identify miRNAs regulating VEGF using systematic reviews and bioinformatics tools. We further validated miRNA expression and VEGF level using qRT-PCR and ELISA, respectively. A total 17 studies were selected using systematic review. 97 miRNAs were found to be up-regulated in serum of NSCLC compared to controls. miR-145 was selected to further validate in clinical samples. Serum miR-145 expression in NSCLC (10.77±3.40) was lower than patient with other lung diseases (25.10±7.90) with p-value of 0.019. The VEGF level in serum of NSCLC was significantly higher than other lung diseases and healthy persons with p-value of 0.003 and 0.002, respectively. However, a weak negative correlation of miR-145 and VEGF in serum of NSCLC was observed without significant difference. In conclusion, the expression of miR-145 and VEGF in NSCLC patients may be involved with lung tumorigenesis; however, the VEGF is not regulated by miR-145 in lung cancer.
Objective: The aim of this study was to describe associated factors of patients with moderate to severe pain after laparoscopic abdominal surgery in Post Anesthetic Care Unit.Material and Methods: This retrospective study included patients who underwent laparoscopic abdominal surgeries (bariatric, colorectal, gynecological, urological, and upper gastrointestinal surgery) between February and July 2019. Demographic data were retrieved from the anesthetic records. Pain score was evaluated by self- rating using verbal numerical rating scale (0-10). Logistic regression was used to obtain independent risk factors of moderate to severe (score 4-10) pain against no or mild pain.Results: Two-hundred and ten patients were included. The incidence of moderate (score 4-6) to severe pain (score 7-10) was 50.0%. Those who suffered from moderate to severe pain required higher consumption of analgesic drugs in recovery room than the other groups, however durations of hospitalization were not different between the two groups (p-value=0.329). This was because the highest intensity of pain was in the first postoperative day. A multivariate logistic regression analysis revealed that abdominal pressure more than 12 mmHg (odd ratio (OR)=1.84, 95% confidence interval (CI) 0.8-4.22, p-value=0.153), and operation time more than 3 hours (OR 1.49, 95% CI 0.86-2.61, p-value=0.158) were independent risk factors of moderate to severe pain after laparoscopic procedureConclusion: High intra-abdominal pressure (≥12 mmHg) and prolonged operation time (>3 hours) are the independent risk factors of moderate and severe pain in laparoscopic surgery.
Introduction This study aimed to investigate factors associated with time-to-referral due to worsening symptoms in patients with laboratory-confirmed COVID-19 in southern Thailand. While underlying diseases have been evaluated to assess COVID-19 severity, the influence of vaccinations and treatments is also crucial. Methods A cohort of 8,638 patients quarantined in home or community isolation with laboratory-confirmed COVID-19 was analyzed. Survival analysis and the Cox proportional hazard ratio were employed to assess factors influencing time-toreferral. Results Age ≥ 60 years, neurologic disorders, cardiovascular disease, and human immunodeficiency virus infection were identified as significant risk factors for severe COVID-19 referral. Patients who received full- or booster-dose vaccinations had a lower risk of experiencing severe symptoms compared to unvaccinated patients. Notably, individuals vaccinated during the Omicron-dominant period had a substantially lower time-to-referral than those unvaccinated during the Delta-dominant period. Moreover, patients vaccinated between 1 and 6 months prior to infection had a significantly lower risk of time-to-referral than the reference group. Discussion These findings demonstrate early intervention in high-risk COVID-19 patients and the importance of vaccination efficacy to reduce symptom severity. The study provides valuable insights for guiding future epidemic management strategies and optimising patient care during infectious disease outbreaks.
An intravenous anesthetic drug, propofol was considered to pose antiemetic action. A randomized controlled trial was conducted to evaluate whether propofol could effectively reduce post-operative nausea and vomiting (PONV) compared to thiopental-nitrous oxide (N2O). One-hundred and eight patients undergoing outpatient gynecologic laparoscopy were assigned to receive 3 techniques of anesthesia; thiopental-N2O (T/N), propofol-N2O (P/N) and total intravenous anesthesia (TIVA) using propofol (P/P). The results showed that in the early period (0-5 hours), post-operative nausea in T/N, P/N and P/P groups was 72 per cent, 44 per cent and 31 per cent, respectively (P = 0.002), and post-operative vomiting was 58 per cent, 36 per cent and 11 per cent respectively (P = 0.00014). Patients in the P/N and P/P groups experienced nausea less frequently than the T/N group [relative risk (RR) = 0.62, (95% CI 0.41-0.93) and RR = 0.42 (0.25-0.72) respectively]. Patients in the P/N and P/P groups experienced vomiting less frequently than the T/N group [RR = 0.62 (0.37-1.04) and RR = 0.19 (0.07-0.5) respectively]. Two patients in the T/N group were admitted because of severe nausea and vomiting. In conclusion, TIVA using propofol and propofol-N2O anesthesia can significantly reduce the incidence of PONV in the early period. Concerning the economic crisis of the country as well as the quality of care, propofol-N2O would be the most appropriate anesthetic of choice.
MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Since aberrant expression of miRNAs has been proposed as usage for blood-based biomarkers, hence reliable techniques for miRNA isolation as well as stability of miRNAs in various stored conditions needs to be explored. This present study aimed to investigate the efficacy of the Trizol-based isolation technique and the stability of miRNAs in stored serum and cDNA derivatives. Total RNA, including miRNAs, was isolated from human serum and a comparison of the efficiency of the Trizol®LS reagent isolation method against the miRNeasy®mini kit was conducted. Expression of RNU6, miR-145, and miR-20a was determined by quantitative real-time polymerase chain reaction (qRT-PCR). We showed that Trizol®LS isolation yielded significantly lower RNA concentrations than that of the miRNeasy®mini kit by approximately 35%. Purity of the isolated RNAs by both methods was similar. RNU6, miR-145, and miR-20a degraded at room temperature, but all genes were stable at 4ºC, -20ºC and -80ºC for a 72-hrs period, in both serum and cDNA storage conditions. In the stored cDNA derivatives, we observed the stability of RNU6, miR-145, and miR-20a for 3 months at -20ºC, and all genes also resisted 4 repeated freeze-thaw cycles at -20ºC. In conclusion, the Trizol-based method is efficient as well as economical to use for quantification of circulating miRNAs. In addition, we proposed that the storage of miRNA-derived cDNAs may be an alternative choice to avoid the stability effect.
MicroRNA (miRNA), a short noncoding RNA, is claimed to be a potential blood-based biomarker. We aimed to identify and evaluate miRNAs as diagnostic biomarkers for non-small cell lung cancer (NSCLC).
Methods:
Profiles of 745 miRNAs were screened in the serum of 8 patients with NSCLC and 8 age- and sex-matched controls using TaqMan low-density arrays (TLDAs) and validated in 25 patients with NSCLC and 30 with other lung diseases (OLs) as well as in 19 healthy persons (HPs). The diagnostic performance of the candidate miRNAs was assessed in 117 cases of NSCLC and 113 OLs using quantitative real-time polymerase chain reaction (qRT-PCR). Differences in miRNA expression between patients with NSCLC and controls were assessed using the Mann–Whitney U test. The area under receiver operating characteristic (ROC) curve (AUC) was obtained based on the logistic regression model.
Results:
Ten miRNAs were found to be differentially expressed between patients with NSCLC and controls, including miR-769, miR-339-3p, miR-339-5p, miR-519a, miR-1238, miR-99a#, miR-134, miR-604, miR-539, and miR-342. The expression of miR-339-3p was significantly higher in patients with NSCLC than in those with OLs (P < 0.001) and HPs (P = 0.020). ROC analysis revealed an miR-339-3p expression AUC of 0.616 [95% confidence interval (CI): 0.561–0.702]. The diagnostic prediction was increased (AUC = 0.706, 95% CI: 0.649–0.779) in the model combining miR-339-3p expression and other known risk factors (i.e., age, smoking status, and drinking status).
Conclusions:
MiR-339-3p was significantly upregulated in patients with NSCLC compared with participants without cancer, suggesting a diagnostic prediction value for high-risk individuals. Therefore, miR-339-3p expression could be a potential blood-based biomarker for NSCLC.
To determine whether the p53 protein expression which is involved in the genesis and progression of various malignant tumours may relate to age, sites or the aggressive histopathological feature of the basal cell carcinoma. METHODS ADN RESULTS: One hundred and fifty-eight basal cell carcinoma specimens from Songklanakarind Hospital, southern Thailand, collected from January 1992 to December 2000, were examined by immunohistochemistry using polyclonal anti-p53-CM1 (Novocastra Laboratories, Newcastle, UK; dilution 1:700). p53 protein expression was demonstrated in 48.7% of cases. The multivariate analysis showed that the aggressive infiltrative histopathological type was significantly associated with p53 expression (odds ratio 2.95, 95% confidence interval 1.10-7.90), whereas age, sun-exposure site, cellular response and fibrosis were not.The p53 expression is found to be related to the aggressive histopathological feature, which may be of predictive value for the behaviour of basal cell carcinoma. However, this result does not support the relation between sun exposure inducing basal cell carcinoma and p53 protein expression.