Predicting the therapeutic response to valproic acid in childhood absence epilepsy through electroencephalogram analysis using machine learning.

Childhood absence epilepsy (CAE) is a common type of idiopathic generalized epilepsy, manifesting as daily multiple absence seizures. Although seizures in most patients can be adequately controlled with first-line antiseizure medication (ASM), approximately 25 % of patients respond poorly to first-line ASM. In addition, an accurate method for predicting first-line medication responsiveness is lacking. We used the quantitative electroencephalogram (QEEG) features of patients with CAE along with machine learning to predict the therapeutic effects of valproic acid in this population. We enrolled 25 patients with CAE from multiple medical centers. Twelve patients who required additional medication for seizure control or who were shifted to another ASM and 13 patients who achieved seizure freedom with valproic acid within 6 months served as the nonresponder and responder groups. Using machine learning, we analyzed the interictal background EEG data without epileptiform discharge before ASM. The following features were analyzed: EEG frequency bands, Hjorth parameters, detrended fluctuation analysis, Higuchi fractal dimension, Lempel-Ziv complexity (LZC), Petrosian fractal dimension, and sample entropy (SE). We applied leave-one-out cross-validation with support vector machine, K-nearest neighbor (KNN), random forest, decision tree, Ada boost, and extreme gradient boosting, and we tested the performance of these models. The responders had significantly higher alpha band power and lower delta band power than the nonresponders. The Hjorth mobility, LZC, and SE values in the temporal, parietal, and occipital lobes were higher in the responders than in the nonresponders. Hjorth complexity was higher in the nonresponders than in the responders in almost all the brain regions, except for the leads FP1 and FP2. Using KNN classification with theta band power in the temporal lobe yielded optimal performance, with sensitivity of 92.31 %, specificity of 76.92 %, accuracy of 84.62 %, and area under the curve of 88.46 %.We used various EEG features along with machine learning to accurately predict whether patients with CAE would respond to valproic acid. Our method could provide valuable assistance for pediatric neurologists in selecting suitable ASM.

The Diagnostic and Prognostic Value of EBUS-TBNA for Intrathoracic Metastasis in Previously Treated Patients With Head and Neck Cancer.

OBJECTIVE: The present study assessed the diagnostic and prognostic significance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for suspected intrathoracic metastasis after HNC treatment. METHODS: A retrospective analysis was conducted on 75 patients with a prior history of head and neck cancer treatment who underwent EBUS-TBNA for suspected intrathoracic metastases between March 2012 and December 2021. RESULTS: A total of 126 targeted lesions, including 107 mediastinal/hilar lymph nodes and 19 intrapulmonary/mediastinal masses, were sampled. The metastatic head and neck cancer (HNC) cases detected by EBUS-TBNA consisted of nasopharyngeal carcinoma (n = 24), oropharyngeal carcinoma (n = 3), hypopharynx carcinoma (n = 6), laryngeal carcinoma (n = 6), and oral cavity carcinoma (n = 6). Cases with negative EBUS-TBNA results consisted of tuberculosis (n = 9), sarcoidosis (n = 3), anthracosis (n = 9), and reactive lymphadenitis (n = 9). Six false-negative cases were found among the 75 patients with suspected intrathoracic metastases. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the EBUS-TBNA procedure for metastatic HNC were 88.2, 100.0, 100.0, 80, and 92.0%, respectively. The diagnosis of HNC intrathoracic metastasis by EBUS-TBNA correlated with an adverse prognosis in terms of overall survival (OS) (P = .008). The log-rank univariate analysis and Cox regression multivariate analysis results indicated that the detection of metastatic HNC through EBUS-TBNA was a significant independent prognostic factor for patients with HNC who had received prior treatment. CONCLUSIONS: Endobronchial ultrasound-guided transbronchial needle aspiration is a safe, effective, and minimally invasive procedure for assessing suspected intrathoracic metastasis in HNC patients after treatment. The intrathoracic metastasis detected by EBUS-TBNA has crucial prognostic significance in previously treated HNC patients.

Molecular genetic mechanisms of interaction between host plants and pathogens.

In recent years, a great number of plant resistance (R) genes and pathogen avirulence (Avr) genes were identified. Exciting breakthroughs were also made on the structural and functional analysis of R proteins and Avr proteins, and the mechanistic interaction between them. Plants have evolved two layers of the immune system to cope with pathogens in the evolutionary processes, which are pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI). In PTI responses, conserved PAMPs are recognized by plant plasma membrane-localized pattern recognition receptors (PRRs) and disease resistance is activated. Furthermore, the ETI immune signaling is activated by the recognition of pathogen Avr proteins by the host R proteins, which usually results in hypersensitive responses at the infection site. In this review, we summarize the progresses on PTI and ETI, and discuss the genetic mechanism of the interaction between plant R gene and pathogen Avr gene in detail. We also envision the new challenges and propose the new strategies for the future investigations on plant resistance molecular breeding.

Clinical practice of basin-shaped hepaticojejunostomy following hilar resection of stage III/IV hilar cholangiocarcinoma.

BACKGROUND: Radical surgery for Bismuth type III/IV hilar cholangiocellular carcinoma, which was usually considered unresectable, seems to improve prognosis by increasing the surgical curability rate. However, the dilemma of multiple billiary stumps and high postoperative complication rate caused by hepato-enteric anastomosis has been the main impediment. Thus, we practiced and introduce a new technique called "basin-shaped" hepaticojejunostomy to improve the treatment. METHODS: Thirty-two cases with Bismuth type III/IV hilar cholangiocarcinoma admitted to our department from Aug. 2013 to Dec. 2015 and who underwent hilar resection and resection segment 4(or plus resection segment 1) were reconstructed by "basin-shaped" hepaticojejunostomy. The clinical data were collected and analyzed. RESULTS: All patients underwent successful R0 high hilar resection following basin-shaped hepaticojejunostomy and were discharged from the hospital without severe postoperative complications. The average operation time for hepato-enteric anastomosis was 42.1 ± 8.5 min. The postoperative bile leakage rate was 3.1% (1/32), and the biliary infection rate was 6.2% (2/32). Within a median follow-up of 25.6 months, none of the patients developed local recurrence around the hepato-enteric anastomosis. CONCLUSIONS: For patients with Bismuth type III/IV hilar cholangiocellular carcinoma who underwent resection segment 4(or plus resection segment 1), basin-shaped hepaticojejunostomy was a safe, simple and valid method for bile duct reconstruction, with a relatively low incidence of postoperative complications.

The efficacy of combination of induction chemotherapy and irreversible electroporation ablation for patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). METHODS: From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. RESULTS: No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. CONCLUSIONS: Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.

Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment.

Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.

A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study.

BACKGROUND: The ability of circulating microRNAs (miRNAs) to detect preclinical hepatocellular carcinoma has not yet been reported. We aimed to identify and assess a serum miRNA combination that could detect the presence of clinical and preclinical hepatocellular carcinoma in at-risk patients. METHODS: We did a three-stage study that included healthy controls, inactive HBsAg carriers, individuals with chronic hepatitis B, individuals with hepatitis B-induced liver cirrhosis, and patients with diagnosed hepatocellular carcinoma from four hospitals in China. We used array analysis and quantitative PCR to identify 19 candidate serum miRNAs that were increased in six patients with hepatocellular carcinoma compared with eight control patients with chronic hepatitis B. Using a training cohort of patients with hepatocellular carcinoma and controls, we built a serum miRNA classifier to detect hepatocellular carcinoma. We then validated the classifiers' ability in two independent cohorts of patients and controls. We also established the classifiers' ability to predict preclinical hepatocellular carcinoma in a nested case-control study with sera prospectively collected from patients with hepatocellular carcinoma before clinical diagnosis and from matched individuals with hepatitis B who did not develop cancer from the same surveillance programme. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared the miRNA classifier with α-fetoprotein at a cutoff of 20 ng/mL (AFP20). FINDINGS: Between Aug 1, 2009, and Aug 31, 2013, we recruited 257 participants to the training cohort, and 352 and 139 participants to the two independent validation cohorts. In the third validation cohort, 27 patients with hepatocellular carcinoma and 135 matched controls were included in the nested case-control study, which ran from Aug 1, 2009, to Aug 31, 2014. We identified a miRNA classifier (Cmi) containing seven differentially expressed miRNAs (miR-29a, miR-29c, miR-133a, miR-143, miR-145, miR-192, and miR-505) that could detect hepatocellular carcinoma. Cmi showed higher accuracy than AFP20 to distinguish individuals with hepatocellular carcinoma from controls in the validation cohorts, but not in the training cohort (AUC 0·826 [95% CI 0·771-0·880] vs 0·814 [0·756-0·872], p=0·72 in the training cohort; 0·817 [0·769-0·865] vs 0·709 [0·653-0·765], p=0·00076 in validation cohort 1; and 0·884 [0·818-0·951] vs 0·796 [0·706-0·886], p=0·042 for validation cohort 2). In all four cohorts, Cmi had higher sensitivity (range 70·4-85·7%) than did AFP20 (40·7-69·4%) to detect hepatocellular carcinoma at the time of diagnosis, whereas its specificity (80·0-91·1%) was similar to that of AFP20 (84·9-100%). In the nested case-control study, sensitivity of Cmi to detect hepatocellular carcinoma was 29·6% (eight of 27 cases) 12 months before clinical diagnosis, 48·1% (n=13) 9 months before clinical diagnosis, 48·1% (n=13) 6 months before clinical diagnosis, and 55·6% (n=15) 3 months before clinical diagnosis, whereas sensitivity of AFP20 was only 7·4% (n=2), 11·1% (n=3), 18·5% (n=5), and 22·2% (n=6) at the corresponding timepoints (p=0·036, p=0·0030, p=0·021, p=0·012, respectively). Cmi had a larger AUC than did AFP20 to identify small-size (AUC 0·833 [0·782-0·883] vs 0·727 [0·664-0·792], p=0·0018) and early-stage (AUC 0·824 [0·781-0·868] vs 0·754 [0·702-0·806], p=0·015) hepatocellular carcinoma and could also detect α-fetoprotein-negative (AUC 0·825 [0·779-0·871]) hepatocellular carcinoma. INTERPRETATION: Cmi is a potential biomarker for hepatocellular carcinoma, and can identify small-size, early-stage, and α-fetoprotein-negative hepatocellular carcinoma in patients at risk. The miRNA classifier could be valuable to detect preclinical hepatocellular carcinoma, providing patients with a chance of curative resection and longer survival. FUNDING: National Key Basic Research Program, National Science and Technology Major Project, National Natural Science Foundation of China.

Transarterial injection of recombinant human type-5 adenovirus H101 in combination with transarterial chemoembolization (TACE) improves overall and progressive-free survival in unresectable hepatocellular carcinoma (HCC).

BACKGROUND: The aim of this study was to determine the clinical benefit of transhepatic arterial chemoembolization (TACE) with or without recombinant human adenovirus type 5 (H101) administration for the treatment of patients with hepatocellular carcinoma (HCC). METHODS: Tumor response, progression-free survival (PFS), and overall survival(OS) were retrospectively evaluated in consecutive patients with unresectable HCC who received TACE with or without H101 between April 2012 and April 2013. RESULTS: Patients with unresectable HCC were treated with transarterial injection of H101 with TACE (H101 group, n = 87) or TACE alone (control group, n = 88). Clinicopathological features were similar between the groups. Treatment response was significantly different between the groups (P = 0.01). In the H101 group, 25 patients demonstrated a complete response (CR, 28.7 %); 28 patients, a partial response (PR, 32.2 %); 23 patients, stable disease (SD, 26.4 %); and 11 patients, progressive disease (PD, 12.6 %). In the control group, 13 patients demonstrated CR (14.8 %); 19, PR (21.6 %); 34, SD (38.6 %); and 22, PD (25 %). OS and PFS was also significantly different between the groups. In the H101 group, median OS and PFS were 12.8 and 10.49 months, whereas in the control group they were 11.6 and 9.72 months, respectively (OS: P = 0.046; PFS: P = 0.044). CONCLUSION: In patients with unresectable HCC, H101 combined with TACE improves OS, PFS and treatment response compared with TACE alone.

Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis.

BACKGROUND: The clinical significance of microRNAs (miRNAs) in intrahepatic cholangiocarcinoma (ICC) is unclear. The objective of this study is to examine the miRNA expression profiles and identify a miRNA signature for the prognosis of ICC. METHODS: Using a custom microarray containing 1,094 probes, the miRNA expression profiles of 63 human ICCs and nine normal intrahepatic bile ducts (NIBD) were assessed. The miRNA signatures were established and their clinical significances in ICC were analyzed. The expression levels of some miRNAs were verified by quantitative real-time RT-PCR (qRT-PCR). RESULTS: Expression profile analysis showed 158 differentially expressed miRNAs between ICC and NIBD, with 77 up-regulated and 81 down-regulated miRNAs. From the 158 differentially expressed miRNAs, a 30-miRNA signature consisting of 10 up-regulated and 20 down-regulated miRNAs in ICC was established for distinguishing ICC from NIBD with 100% accuracy. A separate 3-miRNA signature was identified for predicting prognosis in ICC. Based on the 3-miRNA signature, a formula was constructed to compute a risk score for each patient. The patients with high-risk had significantly lower overall survival and disease-free survival than those with low-risk. The expression level of these three miRNAs detected by microarray was verified by qRT-PCR. Multivariate analysis indicated that the 3-miRNA signature was an independent prognostic predictor. CONCLUSIONS: In this study, a 30-miRNA signature for distinguishing ICC from NIBD, and a 3-miRNA signature for evaluating prognosis of ICC were established, which might be able to serve as biomarkers for prognosis of ICC. Further studies focusing on these miRNAs may shed light on the mechanisms associated with ICC pathogenesis and progression.

Long-term therapy with sorafenib is associated with pancreatic atrophy.

BACKGROUND: Although the short-term adverse effects of sorafenib are well known, few data exist on long-term toxicity. The objective of the present study was to investigate the prevalence of pancreatic atrophy among a cohort of patients with hepatocellular carcinoma (HCC) who were treated with sorafenib for ≥2 y. METHODS: Between March 2007 and December 2013, 31 patients with HCC who were treated with sorafenib for ≥2 y were identified. The effect of pancreatic atrophy and enhancement on incidence of adverse events, tumor response, and overall survival (OS) were assessed. RESULTS: Thirty-one patients with HCC were treated with sorafenib for ≥2 y and met inclusion criteria; 11 patients (35.5%) were Barcelona-clinic liver cancer stage B, whereas 20 patients (64.5%) were Barcelona-clinic liver cancer stage C. Median duration of treatment with sorafenib was 35.2 mo. Pancreatic atrophy and a decrease in pancreatic enhancement occurred in 24 patients (77.4%) and 15 patients (48.4%), respectively. On the basis of the modified response evaluation criteria in solid tumors, four patients (12.9%) had a complete response, 10 patients (32.3%) had a partial response, and 17 patients (54.8%) had stable disease. Patients treated with sorafenib with pancreatic atrophy had a median OS of 49.4 mo (95% confidence interval, 41.2-57.5 mo) compared with 31.2 mo (95% confidence interval, 25.7-36.7 mo) among patients who did not develop pancreatic atrophy (P = 0.009). In contrast, survival was not associated with decreased versus normal enhancement of the pancreas (OS, 47.7 mo versus 41.7 mo, respectively; P = 0.739). CONCLUSIONS: Pancreatic atrophy occurred in many HCC patients after 2 y of treatment with sorafenib. Patients who experienced pancreatic atrophy had a better tumor response and OS.

Impact of oral anti-hepatitis B therapy on the survival of patients with hepatocellular carcinoma initially treated with chemoembolization.

INTRODUCTION: Most hepatocellular carcinomas (HCC) develop in a background of underlying liver disease including chronic hepatitis B. However, the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus (HBV)-related HCC treated with chemoembolization is unclear. This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC. METHODS: A total of 224 HCC patients who successfully underwent chemoembolization were identified, and their survival and other relevant clinical data were reviewed. Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival (OS). RESULTS: The median survival time (MST) was 15.9 (95% confidence interval [CI], 9.5-27.7) months in the antiviral group and 9.6 (95% CI, 7.8-13.7) months in the non-antiviral group (log-rank test, P = 0.044). Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS (P = 0.008). Additionally, a further analysis was based on the stratification of the TNM tumor stages. In the subgroup of early stages, MST was significantly longer in the antiviral-treatment group than in the non-antiviral group (61.8 months [95% CI, 34.8 months to beyond the follow-up period] versus 26.2 [95% CI, 14.5-37.7] months, P = 0.012). Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup (P = 0.006). However, in the subgroup of advanced stages, MST of the antiviral-treated group was comparable to that of the non-antiviral group (8.4 [95% CI, 5.2-13.5] months versus 7.4 [95% CI, 5.9-9.3] months, P = 0.219). Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup. CONCLUSION: Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC, especially in patients with early-stage tumors.

Transbronchial Cryobiopsy Versus Transbronchial Forceps Biopsy for Acute Cellular Rejection Detection in Lung Transplantation: A Meta-Analysis.

BACKGROUND: Transbronchial cryobiopsy (TBCB) provides larger tissue samples and improved sampling depth, but its role in diagnosing acute cellular rejection (ACR) in lung transplant patients is unclear due to limitations in existing studies. To address this, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of TBCB. METHODS: A thorough literature review was conducted to evaluate TBCB in post-lung transplant surveillance, assessing the quality of studies and conducting a meta-analysis comparing diagnostic yields of TBCB and transbronchial forceps biopsy (TBFB), as well as evaluating procedural complications. RESULTS: Our meta-analysis, incorporating 11 studies with a total of 915 patients, showed that TBCB had a diagnostic rate of 38.27% (225/588) for ACR post-lung transplantation, notably higher than the 35.65% (251/704) for TBFB. The inverse-variance weighted odds ratio was calculated at 2.32 (95% confidence interval: 1.24-4.32; p=0.008). Funnel plot analysis indicated no major publication bias. Meta-analysis of 6 studies demonstrated that TBCB, compared to TBFB, significantly increased the diagnostic rate for chronic rejection post-transplantation (25.00% vs 10.93%, p=0.005). Our meta-analysis comparing the safety of TBCB and TBFB in post-lung transplant surveillance found no significant differences in moderate to severe bleeding (5.99% vs 6.31%, p=0.98), or pneumothorax incidence (3.90% vs 3.29%, p=0.75). CONCLUSIONS: Our study indicates that TBCB may enhance the diagnosis of acute and chronic rejection post-lung transplantation with a safety profile comparable to TBFB. Further research and the development of standardized procedures are warranted to ensure the safe and effective application of TBCB in broader clinical practice.

Air Transportation Impact on a Late Preterm Neonate.

BACKGROUND: Neonatal air transportation is a crucial means of moving critically ill or sick neonates to specialized neonatal intensive care units or medical centers for consultation, regardless of distance or geographical limits. Proper preparation and consideration of air transport can help alleviate medical emergencies and ensure safe delivery. However, crewmembers and neonates may face stress during transportation. To date, there are few studies on neonatal air transportation in Taiwan.CASE REPORT: We present the case of a late preterm neonate born with neonatal respiratory distress syndrome and polycythemia, who was also diagnosed with patent ductus arteriosus and mild pulmonary arterial hypertension on echocardiography. Due to disease progression, the neonate underwent endotracheal intubation and was subsequently transported to a medical center in Taiwan via a rotary-wing aircraft at 3 d of age. During takeoff and landing, a temporary oxygen desaturation event occurred. The physiological changes in these patients have seldom been discussed. This case emphasizes the important considerations of neonatal transport in Taiwan.DISCUSSION: The air transport process could be influenced by both the patient's medical condition and environmental factors. In preterm infants with cardiopulmonary conditions, thorough assessment is necessary for ensuring safe transportation.Li S-P, Hsu P-C, Huang C-Y, Wu P-W, Fang H-H. Air transportation impact on a late preterm neonate. Aerosp Med Hum Perform. 2024; 95(4):219-222.

The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients.

BACKGROUND: Even after surgery, hepatocellular carcinoma (HCC) has poor prognosis; adjuvant therapy is needed to improve effectively the outcome of HCC patients. We evaluated the efficacy of cytokine-induced killer (CIK) cell infusion as an adjuvant therapy for postoperative HCC patients. METHODS: A total of 410 patients were studied retrospectively (January 2002 to January 2007): 206 received surgery alone; 204 received surgery and at least four cycles of CIK cell transfusion (CIK group). Kaplan-Meier and Cox regression analyses were used to explore differences in OS between two groups. RESULTS: The CIK group overall survival rates were significantly higher than that of the surgery-alone group (log-rank test; p = 0.0007). Multivariate survival analysis showed that CIK cell treatment was an independent prognostic factor. In subgroup analysis, patients who received ≥8 cycles of CIK cell transfusion exhibited significantly better survival than the <8 cycle group (p = 0.0272). There was no significant difference in overall survival in patients with ≤5-cm tumors between the CIK and surgery-alone groups (p = 0.7567). However, in patients with >5-cm tumors, the CIK group displayed significantly better overall survival than the surgery-alone group (p = 0.0002). CONCLUSIONS: Postoperative immunotherapy with CIK cell transfusion may be an effective adjuvant treatment for improving the outcomes of HCC patients; >8 cycles of CIK cell transfusion may ensure that patients derive maximal benefits. Moreover, patients with large tumors might benefit more from CIK cell adjuvant treatment than patients with small tumors.

Effect of tea polyphenol on oxidative injury in S180 cells induced hepatocarcinoma mice.

The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels.

The preconditioning pulmonary protective effect of volatile isoflurane in acute lung injury is mediated by activation of endogenous iNOS.

PURPOSE: There is still a lack of evidence to support the use of specific anesthetic agents during major operations that could affect the development of postoperative acute lung injury (ALI). This study determined the protective effect of inhaled isoflurane in a rat model of endotoxin-induced ALI. METHODS: Rats were exposed to volatile isoflurane (1.5 % in oxygen) or pure oxygen via a facemask for 2 h. After a 3-h recovery period, rats were reanesthetized and ALI was induced by intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg in 0.5 ml saline). In some animals, a specific inducible nitric oxide synthase (iNOS) inhibitor, 1400W, (10 mg/kg, i.p.) was administered before exposure to isoflurane. Animals were sacrificed 12 h later for analysis. Pulmonary artery vasomotor function and alveolocapillary permeability were assessed. Expression of iNOS and CD11b, and activity of myeloperoxidase in the lung were analyzed. RESULTS: The maximal relaxation response to acetylcholine was significantly potentiated in rats pretreated with isoflurane. Lung wet-to-dry ratio was reduced in the lung of isoflurane-treated animals. Expression of iNOS and CD11b were attenuated in the lung tissue obtained from rats receiving isoflurane. Furthermore, enzymatic activity of myeloperoxidase was also reduced in the lung preexposed to isoflurane. However, these pulmonary protective effects of isoflurane were significantly abolished by pretreatment with 1400W. CONCLUSION: Pretreatment with volatile isoflurane attenuated inflammatory process in the lung tissue of rats with LPS-induced ALI, and this preconditioning pulmonary protective effect was mainly mediated by activation of endogenous iNOS in the lung.

Optimizing Chemotherapy of Pancreatic Acinar Cell Carcinoma: Our Experiences and Pooled Analysis of Literature.

Background: Pancreatic acinar cell carcinoma (PACC) is rare, and its appropriate treatment remains unknown. We aim to explore the characteristics and optimal treatment of it. Methods: The data on clinicopathologic characteristics, molecular alteration, treatment, and survival of patients diagnosed with PACC at the Sun Yat-sen University Cancer Center from 2005 to 2020 were collected. The optimal treatment was explored by co-analyzing our results and published literatures. Results: Twenty-two PACC patients were enrolled. Eight of 17 non-metastatic patients received adjuvant chemotherapy. The patients receiving fluoropyrimidine-based regimen (n = 3) had a better median disease-free survival (mDFS) than those with gemcitabine-based regimen (n = 5) (unreached vs 27 months). Eight metastatic patients received first-line chemotherapy. Four patients received second-line chemotherapy. The objective response rate (ORR) of the fluoropyrimidine-based regimen was 85.7% (6/7), much better than that of the gemcitabine-based regimen (0/5). One patient who had responded to the first-line FOLFIRINOX (5-fluorouracil + oxaliplatin + leucovorin + irinotecan) regimen received olaparib as maintenance treatment for 5 months with good tolerance. Thirty-one published literatures, with a total of 86 cases, were included in the co-analysis. The ORR of the first-line fluoropyrimidine-based regimen (n = 47) was higher than that of gemcitabine-based regimen (n = 39) (59.6% vs 15.3%, P < .001). Eight of 11 patients treated with the FOLFIRINOX regimen achieved partial response (PR). Conclusions: For patients with metastasis, a fluorouracil-based regimen such as FOLFIRINOX may be preferred, and maintenance treatment of poly ADP-ribose polymerase (PARP) inhibitors after effective platinum-containing treatment for breast cancer susceptibility gene (BRCA) mutation patients must be assessed.

Cisplatin and gemcitabine exert opposite effects on immunotherapy with PD-1 antibody in K-ras-driven cancer.

INTRODUCTION: Immunochemotherapy using PD-1/PD-L1 antibodies in combination with chemotherapeutic agents has become a mainstream treatment for cancer patients, but it remains unclear which drug combinations would produce best therapeutic outcome. OBJECTIVES: The purpose of this study was to investigate two common chemotherapeutic drugs, gemcitabine and cisplatin, for their impacts on the therapeutic efficacy of PD-1 antibody in K-ras-driven cancers known to overexpress PD-L1. METHODS: Both in vitro assays and syngeneic mouse tumor models were used in this study. Biochemical and molecular assays were used to determine the effects of drugs on T cell functions in cell culture models and in mouse/human tumor tissues. Allograft tumor models with K-ras mutation were used to investigate the combination effect of gemcitabine or cisplatin with immunotherapy. Data of lung cancer patients with K-ras mutation treated with cisplatin and toripalimab were analyzed to evaluate the clinical relevance of the lab findings. RESULTS: Cisplatin and gemcitabine unexpectedly exert opposite effect on the therapeutic activity of PD-1 antibody in vivo. Gemcitabine antagonizes the therapeutic effect of PD-1 antibody due to its significant inhibition on CD8+ T cell infiltration, which was observed both in mouse tumor allografts and in human pancreatic cancer tissues. In contrast, cisplatin shows synergistic activity with PD-1 antibody by activation of CD8+ T cells through the DNA damage-mediated cGAS-STING sensing mechanism, leading to increase of T cell infiltration and secretion of antitumor cytokines. Clinical data show that a combination of cisplatin with PD-1 antibody toripalimab could be effective in advanced lung cancer patients with K-ras mutation who failed prior therapies. CONCLUSIONS: Our study shows that a key factor in selecting chemotherapeutic agents for immunochemotherapy is the drug's impact on T cell functions, and that cisplatin-based chemotherapy is an excellent choice for combination with immune checkpoint antibody to achieve favorable clinical outcome.

[Genetic analysis and gene mapping of DDF1, a pleiotropic gene involving in both vegetable and reproductive growth in rice].

There are many pleiotropic genes playing key roles in regulating both vegetative growth and reproductive development in plants. A dwarf mutant of rice with deformed flowers, named as ddf1, was identified from indica rice breeding lines. Genetic analysis indicated that ddf1 was resulted from the recessive mutation of a single gene, temporarily named as DDF1. This result suggested that DDF1 is a pleiotropic gene, which controls both vegetative growth and reproductive development in rice. To map this gene, an F2 population was developed by crossing the ddf1 heterozygote with the tropical japonica rice variety DZ60. By means of bulked segregant analysis and small population-based linkage analysis using the published RM-series rice SSR markers, DDF1 was preliminarily mapped in a region between markers RM588 and RM587 on chromosome 6 with the genetic distances of 3.8 cM and 2.4 cM to the two markers, respectively. By developing new SSR markers in this interval according to the published rice genome sequence, we further mapped DDF1 in a 165 kb interval. The results will facilitate cloning of DDF1.

A novel technique of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration in the diagnosis of submucosal recurrence of nasopharyngeal carcinoma after chemoradiotherapy.

BACKGROUND: Recurrence of nasopharyngeal carcinoma (NPC) after chemoradiotherapy is common, but submucosal recurrence of NPC is rare. The final pathological results determine the optimal therapeutic schedule for treatment of NPC recurrence, but tissue retrieval from submucosal lesions is usually difficult. The present study aimed to assess the safety and efficacy of a novel approach of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration (ENUS-TNNA) for submucosal neoplasms in patients with suspected NPC recurrence. METHODS: Between March 2017 and June 2021, 11 post-chemoradiotherapy patients with suspected magnetic resonance imaging (MRI) findings of submucosal recurrence of NPC underwent ENUS-TNNA. The safety and effectiveness of using ENUS-TNNA to sample submucosal neoplasms were evaluated. RESULTS: Needle aspiration biopsies were performed without any incidences in all cases. Out of the 11 patients, nine were diagnosed with submucosal recurrence of NPC via histopathological or cytological evaluations. Of the two puncture-negative cases, one patient had atypical imaging findings and clinical manifestations and was therefore followed-up using MRI. After follow-up for 3 years, this patient was still considered to be cancer-free due to the shrinking diameters of the submucosal lesions. For the other puncture-negative patient, submucosal biopsy samples were obtained using a surgical method. Pathological examination of these biopsies revealed that an angiosarcoma had developed after radiotherapy. There were no severe complications that occurred during the ENUS-TNNA procedure. CONCLUSION: ENUS-TNNA is a safe, effective, and minimally invasive approach to obtain tissue samples from the submucosal region of the nasopharynx for patients with suspected NPC recurrence.