Utilizing disease transmission and response capacities to optimize covid-19 control in Malaysia.

OBJECTIVES: Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia. METHODS: Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed. RESULTS: CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p < 0.001] with the COVID-19 cases. The estimated SL was strongly correlated with COVID-19 cases (ρ = 0.845, p < 0.001) and responded well to the various COVID-19 case trends during the pandemic. SL changes occurred earlier during the increase of cases but slower during the decrease, indicating a conservative response. The automated web-based system developed produced daily real-time CT, RC, and SL for the COVID-19 pandemic. CONCLUSIONS: The indicators selected and combinations formed were able to generate validated daily CT and RC levels for Malaysia. Subsequently, the CT and RC levels were able to provide accurate and sensitive information for the estimation of SL which provided valuable evidence on the progression of the pandemic and movement restriction adjustment for the control of Malaysia.

Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer.

BACKGROUND: Accurate preoperative prediction of lymph node metastasis (LNM) in esophageal cancer (EC) patients is of crucial clinical significance for treatment planning and prognosis. AIM: To develop a clinical radiomics nomogram that can predict the preoperative lymph node (LN) status in EC patients. METHODS: A total of 32 EC patients confirmed by clinical pathology (who underwent surgical treatment) were included. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy, and its correlation with LNM was analyzed. Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python. Feature extraction, data dimensionality reduction, and feature selection were performed using XGBoost model and leave-one-out cross-validation. Multivariable logistic regression analysis was used to establish the prediction model, which included radiomics features, LN status from computed tomography (CT) reports, and B7-H3 mRNA expression, represented by a radiomics nomogram. Receiver operating characteristic area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical application value of the model. RESULTS: The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis, and the difference was statistically significant (P < 0.05). The AUC value in the receiver operating characteristic (ROC) curve was 0.718 (95%CI: 0.528-0.907), with a sensitivity of 0.733 and specificity of 0.706, indicating good diagnostic performance. The individualized clinical prediction nomogram included radiomics features, LN status from CT reports, and B7-H3 mRNA expression. The ROC curve demonstrated good diagnostic value, with an AUC value of 0.765 (95%CI: 0.598-0.931), sensitivity of 0.800, and specificity of 0.706. DCA indicated the practical value of the radiomics nomogram in clinical practice. CONCLUSION: This study developed a radiomics nomogram that includes radiomics features, LN status from CT reports, and B7-H3 mRNA expression, enabling convenient preoperative individualized prediction of LNM in EC patients.

Description of the COVID-19 epidemiology in Malaysia.

Introduction: Since the COVID-19 pandemic began, it has spread rapidly across the world and has resulted in recurrent outbreaks. This study aims to describe the COVID-19 epidemiology in terms of COVID-19 cases, deaths, ICU admissions, ventilator requirements, testing, incidence rate, death rate, case fatality rate (CFR) and test positivity rate for each outbreak from the beginning of the pandemic in 2020 till endemicity of COVID-19 in 2022 in Malaysia. Methods: Data was sourced from the GitHub repository and the Ministry of Health's official COVID-19 website. The study period was from the beginning of the outbreak in Malaysia, which began during Epidemiological Week (Ep Wk) 4 in 2020, to the last Ep Wk 18 in 2022. Data were aggregated by Ep Wk and analyzed in terms of COVID-19 cases, deaths, ICU admissions, ventilator requirements, testing, incidence rate, death rate, case fatality rate (CFR) and test positivity rate by years (2020 and 2022) and for each outbreak of COVID-19. Results: A total of 4,456,736 cases, 35,579 deaths and 58,906,954 COVID-19 tests were reported for the period from 2020 to 2022. The COVID-19 incidence rate, death rate, CFR and test positivity rate were reported at 1.085 and 0.009 per 1,000 populations, 0.80 and 7.57%, respectively, for the period from 2020 to 2022. Higher cases, deaths, testing, incidence/death rate, CFR and test positivity rates were reported in 2021 and during the Delta outbreak. This is evident by the highest number of COVID-19 cases, ICU admissions, ventilatory requirements and deaths observed during the Delta outbreak. Conclusion: The Delta outbreak was the most severe compared to other outbreaks in Malaysia's study period. In addition, this study provides evidence that outbreaks of COVID-19, which are caused by highly virulent and transmissible variants, tend to be more severe and devastating if these outbreaks are not controlled early on. Therefore, close monitoring of key epidemiological indicators, as reported in this study, is essential in the control and management of future COVID-19 outbreaks in Malaysia.

Characterization of tumor microbiome and associations with prognosis in intrahepatic cholangiocarcinoma.

BACKGROUND: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. METHODS: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. RESULTS: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. CONCLUSION: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC.

Progress in mechanism-based diagnosis and treatment of tuberculosis comorbid with tumor.

Tuberculosis (TB) and tumor, with similarities in immune response and pathogenesis, are diseases that are prone to produce autoimmune stress response to the host immune system. With a symbiotic relationship between the two, TB can facilitate the occurrence and development of tumors, while tumor causes TB reactivation. In this review, we systematically sorted out the incidence trends and influencing factors of TB and tumor, focusing on the potential pathogenesis of TB and tumor, to provide a pathway for the co-pathogenesis of TB comorbid with tumor (TCWT). Based on this, we summarized the latest progress in the diagnosis and treatment of TCWT, and provided ideas for further exploration of clinical trials and new drug development of TCWT.

Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Novel Pharmaceutical Cocrystals of Tegafur: Synthesis, Performance, and Theoretical Studies.

PURPOSE: Tegafur (TF) is one of the most important clinical antitumor drugs with poor water solubility, severely reducing its bioavailability. This work develops new cocrystals to improve the solubility of TF and systematically investigates the intermolecular interactions to provide new insights into the formation of cocrystal and changes in physicochemical properties. METHOD: In this paper, two new 1:1 cocrystals of TF with 2,4 dihydroxybenzoic acid (2,4HBA) and p-nitrophenol (PNP) were synthesized. The cocrystal products were identified and characterized by various solid state analysis techniques. And the high performance liquid chromatography (HPLC) was conducted to determine the solubility and dissolution rate of TF and cocrystals. Moreover, the quantum chemistry calculations of crystal structure provided theoretical support for the results. RESULT: Compared with pure TF, the solubility and dissolution rate of TF-2,4HBA is significantly increased in a pH 6.8 buffer at 37°C. Under accelerated storage conditions (40°C, 75% RH), all cocrystal exhibits excellent stability over 8 weeks. Hirshfeld surface (HS) analysis, atoms in molecules (AIM) analysis, interaction region indicator (IRI) analysis, molecular electrostatic potential surface (MEPS) analysis and frontier molecular orbital (HOMO-LUMO) analysis were integrated to understand the hydrogen bonding interaction more comprehensively. The simulation results are in good agreement with the experimental data. The results show that the analysis of physical and chemical properties of TF-PNP cocrystal and TF crystal by quantum chemistry method is reliable at molecular level. CONCLUSION: These results are helpful to provide guiding methods in the cocrystal development and theoretical study of tegafur.

Trends and Age-Period-Cohort Effect on Incidence of Male Breast Cancer from 1980 to 2019 in Taiwan and the USA.

Although male breast cancer (MBC) is globally rare, its incidence significantly increased from 1990 to 2017. The aim of this study was to examine variations in the trends of MBC incidence between populations in Taiwan and the USA from 1980 to 2019. The Taiwan Cancer Registry database and the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute of the USA were used. The age-standardized incidence rate was calculated using the world standard population in 2000. The long-term trends of the age, time period, and birth cohort effect on MBC incidence rates were estimated using the SEER Age-Period-Cohort Web Tool. The results revealed that the incidence of MBC in both countries increased from 2010 to 2019 (Taiwan: average annual percentage change (AAPC) = 2.59%; USA: AAPC = 0.64%). The age and period effects on the incidence rates in both countries strengthened, but the cohort effect was only identified in Taiwan (Rate ratio: 4.03). The identified cohort effect in this study bears resemblance to that noted in a previous investigation on female breast cancer in Taiwan. This suggests the possible presence of common environmental factors influencing breast cancer incidence in both genders, such as a high fat diet and xenoestrogen.

Forecasting the effects of vaccination on the COVID-19 pandemic in Malaysia using SEIRV compartmental models.

OBJECTIVES: This study aimed to develop susceptible-exposed-infectious-recovered-vaccinated (SEIRV) models to examine the effects of vaccination on coronavirus disease 2019 (COVID-19) case trends in Malaysia during Phase 3 of the National COVID-19 Immunization Program amidst the Delta outbreak. METHODS: SEIRV models were developed and validated using COVID-19 case and vaccination data from the Ministry of Health, Malaysia, from June 21, 2021 to July 21, 2021 to generate forecasts of COVID-19 cases from July 22, 2021 to December 31, 2021. Three scenarios were examined to measure the effects of vaccination on COVID-19 case trends. Scenarios 1 and 2 represented the trends taking into account the earliest and latest possible times of achieving full vaccination for 80% of the adult population by October 31, 2021 and December 31, 2021, respectively. Scenario 3 described a scenario without vaccination for comparison. RESULTS: In scenario 1, forecasted cases peaked on August 28, 2021, which was close to the peak of observed cases on August 26, 2021. The observed peak was 20.27% higher than in scenario 1 and 10.37% lower than in scenario 2. The cumulative observed cases from July 22, 2021 to December 31, 2021 were 13.29% higher than in scenario 1 and 55.19% lower than in scenario 2. The daily COVID-19 case trends closely mirrored the forecast of COVID-19 cases in scenario 1 (best-case scenario). CONCLUSIONS: Our study demonstrated that COVID-19 vaccination reduced COVID-19 case trends during the Delta outbreak. The compartmental models developed assisted in the management and control of the COVID-19 pandemic in Malaysia.

Vibration rejection of phased array telescope systems via disturbance-propagation-characteristics-based feedforward control.

Vibration rejection is one of the key techniques to stabilize the line of sight (LOS) for phased array telescope systems. Conventionally, feedback control based on image sensors is mainly used to correct the tip/tilt errors caused by disturbances and to keep the LOS stable. However, it is restricted by the sampling rate and time delay of image sensors, leading to a limited closed-loop bandwidth. Disturbances in the middle and high frequencies are hard to suppress. In this paper, disturbance-propagation-characteristics-based feedforward control is proposed to overcome these problems. A theoretical imaging model of the phased array telescope is developed to analyze the LOS disruption caused by disturbance. In addition, to improve the disturbance suppression bandwidth and correction accuracy of the system, the disturbance propagation characteristics of the phased array telescope system are analyzed. Combined with the disturbance feedforward, targeted compensation is achieved for the sub-apertures. Finally, a comparative experiment is carried out based on the self-developed Fizeau phased array telescope system to verify the superiority of the proposed method.

The effects of the COVID-19 pandemic on dengue cases in Malaysia.

Background: Globally, the COVID-19 pandemic has affected the transmission dynamics and distribution of dengue. Therefore, this study aims to describe the impact of the COVID-19 pandemic on the geographic and demographic distribution of dengue incidence in Malaysia. Methods: This study analyzed dengue cases from January 2014 to December 2021 and COVID-19 confirmed cases from January 2020 to December 2021 which was divided into the pre (2014 to 2019) and during COVID-19 pandemic (2020 to 2021) phases. The average annual dengue case incidence for geographical and demographic subgroups were calculated and compared between the pre and during the COVID-19 pandemic phases. In addition, Spearman rank correlation was performed to determine the correlation between weekly dengue and COVID-19 cases during the COVID-19 pandemic phase. Results: Dengue trends in Malaysia showed a 4-year cyclical trend with dengue case incidence peaking in 2015 and 2019 and subsequently decreasing in the following years. Reductions of 44.0% in average dengue cases during the COVID-19 pandemic compared to the pre-pandemic phase was observed at the national level. Higher dengue cases were reported among males, individuals aged 20-34 years, and Malaysians across both phases. Weekly dengue cases were significantly correlated (ρ = -0.901) with COVID-19 cases during the COVID-19 pandemic. Conclusion: There was a reduction in dengue incidence during the COVID-19 pandemic compared to the pre-pandemic phase. Significant reductions were observed across all demographic groups except for the older population (>75 years) across the two phases.

Association of BRAF Variants With Disease Characteristics, Prognosis, and Targeted Therapy Response in Intrahepatic Cholangiocarcinoma.

Importance: BRAF variants are associated with tumor progression; however, the prevalence of BRAF variant subtypes and their association with disease characteristics, prognosis, and targeted therapy response in patients with intrahepatic cholangiocarcinoma (ICC) are largely unknown. Objective: To explore the association of BRAF variant subtypes with disease characteristics, prognosis, and targeted therapy response in patients with ICC. Design, Setting, and Participants: In this cohort study, 1175 patients who underwent curative resection for ICC from January 1, 2009, through December 31, 2017, were evaluated at a single hospital in China. Whole-exome sequencing, targeted sequencing, and Sanger sequencing were performed to identify BRAF variants. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed using Cox proportional hazards regression. Associations between BRAF variants and targeted therapy response were tested in 6 BRAF-variant, patient-derived organoid lines and in 3 of the patient donors of those lines. Data were analyzed from June 1, 2021, to March 15, 2022. Interventions: Hepatectomy in patients with ICC. Main Outcomes and Measures: The association of BRAF variant subtypes with OS and DFS. Results: Of 1175 patients with ICC, the mean (SD) age was 59.4 (10.4) years and 701 (59.7%) were men. A total of 20 different subtypes of BRAF somatic variance affecting 49 patients (4.2%) were identified; V600E was the most frequent allele in this cohort, accounting for 27% of the identified BRAF variants, followed by K601E (14%), D594G (12%), and N581S (6%). Compared with patients with non-V600E BRAF variants, patients with BRAF V600E variants were more likely to have large tumor size (10 of 13 [77%] vs 12 of 36 [33%]; P = .007), multiple tumors (7 of 13 [54%] vs 8 of 36 [22%]; P = .04), and more vascular/bile duct invasion (7 of 13 [54%] vs 8 of 36 [22%]; P = .04). Multivariate analysis revealed that BRAF V600E variants, but not overall BRAF variants or non-V600E BRAF variants, were associated with poor OS (hazard ratio [HR], 1.87; 95% CI, 1.05-3.33; P = .03) and DFS (HR, 1.66; 95% CI, 1.03-2.97; P = .04). There were also broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Conclusions and Relevance: The findings of this cohort study suggest that there are broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Identifying and classifying BRAF variants may be able to help guide precise treatment for patients with ICC.

Finite element analysis of stress in oral mucosa and titanium mesh interface.

BACKGROUND: The stiffness of titanium mesh is a double-blade sword to repair larger alveolar ridges defect with excellent space maintenance ability, while invade the surrounding soft tissue and lead to higher mesh exposure rates. Understanding the mechanical of oral mucosa/titanium mesh/bone interface is clinically meaningful. In this study, the above relationship was analyzed by finite elements and verified by setting different keratinized tissue width in oral mucosa. METHODS: Two three-dimensional finite element models were constructed with 5 mm keratinized tissue in labial mucosa (KM cases) and 0 mm keratinized tissue in labial mucosa (LM cases). Each model was composed of titanium mesh, titanium screws, graft materials, bone, teeth and oral mucosa. After that, a vertical (30 N) loadings were applied from both alveolar ridges direction and labial mucosa direction to stimulate the force from masticatory system. The displacements and von Mises stress of each element at the interfaces were analyzed. RESULTS: Little displacements were found for titanium mesh, titanium screws, graft materials, bone and teeth in both LM and KM cases under different loading conditions. The maximum von Mises stress was found around the lingual titanium screw insertion place for those elements in all cases. The keratinized tissue decreased the displacement of oral mucosa, decreased the maximum von Mises stress generated by an alveolar ridges direction load, while increased those stress from labial mucosa direction load. Only the von Mises stress of the KM cases was all lower than the tensile strength of the oral mucosa. CONCLUSION: The mucosa was vulnerable under the increasing stress generated by the force from masticatory system. The adequate buccal keratinized mucosa width are critical factors in reducing the stress beyond the titanium mesh, which might reduce the titanium exposure rate.

Prevalence and Determinants of Depressive Symptoms among Young Adolescents in Malaysia: A Cross-Sectional Study.

Depression is the most common mental health problem affecting adolescents globally, wherein its increasing prevalence together with the negative health impacts escalates the need for further research in this area. This work determined the prevalence and factors associated with depressive symptoms among young adolescents in Malaysia. A total of 1350 adolescent aged 13 to 14 years in school across nine secondary schools in Selangor state, Malaysia participated in a cross-sectional study. Independent variables were examined using the using the Global School-Based Student Health Survey included age, gender, ethnicity, alcohol intake, smoking and illicit drug use, loneliness, bullying, parental marital status, income and supervision; and the Health Literacy and Stigma questionnaire examined mental health literacy levels. Depressive symptoms were the dependent variable which was examined using the Center for Epidemiology Study Depression (CESD) instrument. Prevalence of depressive symptoms among all participants was 19 % (95% CI [16.9, 21.2]), with a higher prevalence of depressive symptoms being reported among females 26.3% (95% CI [23.0, 29.8]) compared to males 11.7% (95% CI [9.4, 14.4]). Determinants namely females (AOR = 3.83; 95% CI [2.66, 5.52]), smoking (AOR = 6.16; 95% CI [3.15, 12.05]), been bullied (AOR = 3.70; 95% CI [2.51, 5.47]), felt lonely (AOR = 10.46; 95% CI [7.09, 15.42]) and having no parental supervision (AOR = 1.79; 95% CI [1.26, 2.53]) significantly increased the odds of depressive symptoms among all adolescents in the multivariate model. In addition, feeling lonely, being bullied and smoking were identified as common significant determinants of depressive symptoms across both genders. Feeling lonely (65% to 71%) and being bullied (10% to 19%) were ranked as the most important determinants of depressive symptoms among young adolescents. Tackling these factors would be instrumental in helping decision makers formulate depression prevention strategies and activities for adolescents.

Secular-Trend Analysis of the Incidence Rate of Lung Squamous Cell Carcinoma in Taiwan.

Lung cancer is the leading cause of cancer deaths worldwide, and squamous cell carcinoma (SQC) is Taiwan's second most common lung carcinoma histotype. This study aimed to investigate changes in the long-term trend of the SQC incidence rate in Taiwan. SQC cases between 1985 and 2019 were adopted from Taiwan's Cancer Registry System; the age-adjusted incidence rate was calculated using the World Standard Population in 2000. The long-term trends of the age, period, and birth cohort effect of SQC incidence rates were estimated using the SEER Age-Period-Cohort Web Tool. The results revealed that the incidence of lung carcinoma in Taiwan increased, while the incidence of SQC exhibited a slight decrease during this study period. The age rate ratio (ARR) of the incidence rate in men declined gradually, and the period effect changed more slowly for women than men. The cohort effect formed a bimodal curve. The annual percentage change results for women indicated that the ARR decreased from 1.652 (95% confidence interval (CI): 1.422, 1.9192) at 30 to 34 years to 0.559 (95% CI: 0.4988, 0.6265) at 75 to 79 years; the period effect decreased from 1.2204 (95% CI: 1.1148, 1.336) in 1995 to 1999 to 0.608 (95% CI: 0.5515, 0.6704) in 2015 to 2019, with a greater decline in the later period. The cohort effect was unimodal, with the SQC risk value peaking in the 1915 birth cohort and exhibiting a steady decline thereafter. The results of this study suggest that a decrease in the smoking rate may be the reason for the decline in the incidence of SQC, and we observed a similar trend between SQC and the smoking rate in men.

Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

Pancreatic paraganglioma with multiple lymph node metastases found by spectral computed tomography: A case report and review of the literature.

BACKGROUND: Primary pancreatic paraganglioma is exceedingly rare. Most patients with pancreatic paraganglioma lack a typical clinical presentation, and the tumor is difficult to accurately differentiate from other pancreatic neuroendocrine tumors, making the misdiagnosis rate extremely high. Surgical excision is the primary treatment modality but is considered high risk. Because of its rich vascularity, the tumor easily bleeds during surgery, especially malignant paragangliomas invading large blood vessels. Thus, a thorough preoperative evaluation of the tumor is necessary. Here, we report a primary malignant pancreatic paraganglioma, the second such case in a young patient that was successfully resected surgically. CASE SUMMARY: A 26-year-old female patient was admitted to the hospital with unexplained abdominal pain. Dual-layer spectral-detector computed tomography (DLCT) revealed a mixed density mass in the pancreatic body and tail. The patient was transferred to our hospital after previous failed surgical resection at other hospitals. The patient and her family strongly desired surgery. After a thorough preoperative evaluation and adequate preparation, a large mass with the greatest dimension of 8.0 cm was successfully resected. The final pathological diagnosis was malignant paraganglioma. The patient was discharged in good condition 2 wk postoperatively. CONCLUSION: The rare malignant pancreatic paraganglioma reported here was difficult to diagnose preoperatively. Early filling of the draining vein may be a crucial diagnostic imaging feature. DLCT can provide more precise information for surgical resection through dual-energy imaging.

Genomic evolution and the impact of SLIT2 mutation in relapsed intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is aggressive and has high rates of relapse, conferring poor long-term survival after curative resection. Little is known about the genomic evolution that occurs during ICC relapse. APPROACH AND RESULTS: We conducted whole-exome sequencing of 30 paired primary and relapsed tumors from 10 patients with ICC who received curative resection. We sought to identify frequently altered genes, infer tumor subclonal architectures, and track genomic evolution from primary to relapsed tumors. We examined functional effects and the mechanism of action of SLIT2, a gene specifically mutated in relapsed tumors, on tumor growth and metastasis and the tumor microenvironment. Our results indicated that relapsed ICCs were genetically derived from intrahepatic dissemination of primary tumors. However, they acquired additional mutations while maintaining most drivers, such as TP53 and IDH1. Multiregion sequencing suggested polyclonal seeding of ICC dissemination. Four of 10 relapsed ICCs acquired SLIT2 mutations that were not present in the corresponding primary tumors. Validation in an expanded sample revealed SLIT2 mutations in 2.3% (1/44) of primary ICCs and 29.5% (13/44) of relapsed ICCs. Biofunctional investigations revealed that inactivating mutation of SLIT2 resulted in activation of PI3K-Akt signaling in ICC cells, directly enhanced neutrophil chemotaxis, mediated tumor-associated neutrophil infiltration, and contributed to ICC growth and metastasis. CONCLUSIONS: We characterized genomic evolution during ICC relapse and identified SLIT2 as a driver of tumor dissemination and tumor-associated neutrophil infiltration.