Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Enantioselective formal total synthesis of dihydrospirotryprostatin B.

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

Spatial profiles of the bacterial microbiota throughout the gastrointestinal tract of dairy goats.

The gastrointestinal tract (GIT) is stationed by a dynamic and complex microbial community with functions in digestion, metabolism, immunomodulation, and reproduction. However, there is relatively little research on the composition and function of microorganisms in different GIT segments in dairy goats. Herein, 80 chyme samples were taken from ten GIT sites of eight Xinong Saanen dairy goats and then analyzed and identified the microbial composition via 16S rRNA V1-V9 amplicon sequencing. A total of 6669 different operational taxonomic units (OTUs) were clustered, and 187 OTUs were shared by ten GIT segments. We observed 264 species belonging to 23 different phyla scattered across ten GITs, with Firmicutes (52.42%) and Bacteroidetes (22.88%) predominating. The results revealed obvious location differences in the composition, diversity, and function of the GIT microbiota. In LEfSe analysis, unidentified_Lachnospiraceae and unidentified_Succinniclassicum were significantly enriched in the four chambers of stomach, with functions in carbohydrate fermentation to compose short-chain fatty acids. Aeriscardovia, Candidatus_Saccharimonas, and Romboutsia were significantly higher in the foregut, playing an important role in synthesizing enzymes, amino acids, and vitamins and immunomodulation. Akkermansia, Bacteroides, and Alistipes were significantly abundant in the hindgut to degrade polysaccharides and oligosaccharides, etc. From rumen to rectum, α-diversity decreased first and then increased, while ß-diversity showed the opposite trend. Metabolism was the major function of the GIT microbiome predicted by PICRUSt2, but with variation in target substrates along the regions. In summary, GIT segments play a decisive role in the composition and functions of microorganisms. KEY POINTS: • The jejunum and ileum were harsh for microorganisms to colonize due to the presence of bile acids, enzymes, faster chyme circulation, etc., exhibiting the lowest α-diversity and the highest ß-diversity. • Variability in microbial profiles between the three foregut segments was greater than four chambers of stomach and hindgut, with a higher abundance of Firmicutes dominating than others. • Dairy goats dominated a higher abundance of Kiritimatiellaeota than cows, which was reported to be associated with fatty acid synthesis.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

Survival benefit from adjuvant TACE combined with Lenvatinib for patients with hepatocellular carcinoma and microvascular invasion after curative hepatectomy.

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

Deep Learning Bridged Bioactivity, Structure, and GC-HRMS-Readable Evidence to Decipher Nontarget Toxicants in Sediments.

Identifying causative toxicants in mixtures is critical, but this task is challenging when mixtures contain multiple chemical classes. Effect-based methods are used to complement chemical analyses to identify toxicants, yet conventional bioassays typically rely on an apical and/or single endpoint, providing limited diagnostic potential to guide chemical prioritization. We proposed an event-driven taxonomy framework for mixture risk assessment that relied on high-throughput screening bioassays and toxicant identification integrated by deep learning. In this work, the framework was evaluated using chemical mixtures in sediments eliciting aryl-hydrocarbon receptor activation and oxidative stress response. Mixture prediction using target analysis explained <10% of observed sediment bioactivity. To identify additional contaminants, two deep learning models were developed to predict fingerprints of a pool of bioactive substances (event driver fingerprint, EDFP) and convert these candidates to MS-readable information (event driver ion, EDION) for nontarget analysis. Two libraries with 121 and 118 fingerprints were established, and 247 bioactive compounds were identified at confidence level 2 or 3 in sediment extract using GC-qToF-MS. Among them, 12 toxicants were analytically confirmed using reference standards. Collectively, we present a "bioactivity-signature-toxicant" strategy to deconvolute mixtures and to connect patchy data sets and guide nontarget analysis for diverse chemicals that elicit the same bioactivity.

Distribution patterns of the two genetic groups of Corbicula fluminea in a lotic-lentic system.

Differences in local habitat conditions are often implicated as drivers for morphological and genetic divergence in natural populations. However, there are still relatively few studies regarding how divergent habitats influence patterns for morphotypes and genetic lineages in aquatic invertebrates. In this study, we explored the morphological patterns, genetic divergence, and distributions of a bivalve, Corbicula fluminea, in a lotic-lentic system. Sampling locations included lotic, ecotone, and lentic habitats. First, we found two lineages (Lineages A and B) with significant genetic divergence that primarily corresponded to two morphotypes (Morphs D and C) of C. fluminea. Lineage A consisted of 88.68% Morph D (shell sculpture: 8-14 ridges/cmsh) and 11.32% Morph C (shell sculpture: 15 ridges/cmsh) individuals and had genetic similarity to invasive populations. Lineage B consisted of only Morph C (shell sculpture: 15-23 ridges/cmsh). Second, we revealed clear effects of habitat on the spatial distribution patterns for the two lineages of C. fluminea. Lineage A was dominant in lotic habitats, with a significantly higher density than that of Lineage B in these locations. Lineage B was dominant in lentic habitats. However, both lineages had their highest densities in the ecotone habitat, without clear dominance and no significant difference in density between groups. Individuals of Lineages A and B are different in shell morphology, which may be related to a benefit trade-off between shell shapes that allow for rapid burrowing and holding position in different flow conditions. The distribution patterns indicate that Lineages A and B may not prefer uniquely lotic and lentic habitats, but each lineage is more tolerant to one habitat type, respectively. Generally, our study established a correlation among morphotypes, lineages, and different habitats for C. fluminea along a lotic-lentic gradient system, which has important implementations for fisheries management units and for understanding the role of habitat preference for this species in monitoring for pioneer dispersal in invasive species management.

Efficacy of a sepsis clinical decision support system in identifying patients with sepsis in the emergency department.

BACKGROUND: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. METHODS: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to sixfold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction (International Classification of Diseases, Tenth Revision, Clinical Modification) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. RESULTS: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). CONCLUSION: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis.

Clinical Observation and Cause Analysis of Perioperative Superior Cluneal Neuralgia in Vertebral Augmentation.

BACKGROUND: In our clinical practice, we observed that some osteoporotic vertebral compression fracture patients undergoing vertebral augmentation exhibited pain in the iliac crest region. This pain aligned with the diagnostic criteria for superior cluneal neuralgia (SCN) and affected treatment satisfaction. OBJECTIVE: This study aims to clinically observe patients undergoing vertebral augmentation in a hospital setting and analyze the etiology and risk factors associated with SCN. STUDY DESIGN: Retrospective cohort study. SETTING: Inpatient population of a single center. METHODS: We retrospectively analyzed clinical data from 630 patients who underwent vertebral augmentation in our hospital from March 2022 to March 2023. Fifty-two patients enrolled in the study experienced pain that met the diagnostic criteria for superior cluneal neuralgia during the perioperative period of the vertebral augmentation procedures. Those patients were divided into 2 subgroups according to the conditions involved in the occurrence of SCN: Group A (26 patients) had either no preoperative SCN but developed it postoperatively, or had preoperative SCN that worsened or did not alleviate postoperatively. Group B (26 patients) had preoperative SCN that was relieved postoperatively. Additionally, 52 consecutive patients in March 2022 to March 2023. who did not experience SCN during the perioperative period were selected as the control group (Group C). Variables such as surgical segment, age, height, weight, body mass index, duration of hospitalization, chronic low back pain (CLBP), duration of pain, anesthesia, surgical approach, fracture pattern, preoperative visual analog scale (pre-op VAS) score, intraoperative VAS score, one-day VAS score, one-month VAS score, lumbar sacral angle, and sacral tilt angle were statistically described and analyzed. RESULTS: In our hospital, the incidence of SCN during the perioperative period of vertebral augmentation procedures is 8.25% (52/630). Among all the segments of patients who developed SCN during the perioperative period, the L1 segment had the highest proportion, which was 29.03% and 35.14% in Groups A and B, respectively. Group B and Group C showed significant differences in duration of hospitalization (P = 0.012), pre-op VAS scores (P = 0.026), and CLBP (P < 0.001). Group A had significantly higher VAS scores preoperatively (P = 0.026) and intraoperatively (P = 0.004) and in CLBP (P = 0.001) than did Group C. LIMITATIONS: This is a retrospective study. Single-center noncontrolled studies may introduce selection bias. The small sample size in each group might have also led to bias. CONCLUSION: Perioperative SCN associated with vertebral augmentation is significantly correlated with preoperative VAS scores and CLBP. In addition, intraoperative VAS scores might be a factor contributing to the nonalleviation or exacerbation of postoperative SCN.

The effect of different fixation systems on oblique lumbar interbody fusion under vibration conditions.

Despite the fact that lower back pain caused by degenerative lumbar spine pathologies seriously affects the quality of life, however, there is a paucity of research on the biomechanical properties of different auxiliary fixation systems for its primary treatment (oblique lumbar interbody fusion) under vibratory environments. In order to study the effects of different fixation systems of OLIF surgery on the vibration characteristics of the human lumbar spine under whole-body vibration (WBV), a finite element (FE) model of OLIF surgery with five different fixation systems was established by modifying a previously established model of the normal lumbar spine (L1-S1). In this study, a compressive follower load of 500 N and a sinusoidal axial vertical load of ±40 N at the frequency of 5 Hz with a duration of 0.6 s was applied. The results showed that the bilateral pedicle screw fixation model had the highest resistance to cage subsidence and maintenance of disc height under WBV. In contrast, the lateral plate fixation model exerted very high stresses on important tissues, which would be detrimental to the patient's late recovery and reduction of complications. Therefore, this study suggests that drivers and related practitioners who are often in vibrating environments should have bilateral pedicle screws for OLIF surgery, and side plates are not recommended to be used as a separate immobilization system. Additionally, the lateral plate is not recommended to be used as a separate fixation system.

Diagnostic utility of in vivo confocal microscopy in Acanthamoeba keratitis following corneal crosslinking.

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening complication of corneal collagen crosslinking (CXL) for keratoconus. In this report, we describe an early adolescent male who underwent routine CXL for progressive keratoconus in his left eye. Preprocedural left visual acuity (VA) was 6/9. At day 5 postprocedure, multifocal corneal infiltrates were identified. Corneal scrape, bandage contact lens cultures and herpetic and Acanthamoeba PCR were negative. In vivo, confocal microscopy (IVCM) identified Acanthamoeba cysts within the corneal stroma. Intensive amoebicidal therapy was initiated, but recovery was complicated by significant inflammation, resulting in widespread aggressive corneal vascularisation necessitating topical steroids and steroid-sparing agents. At 10 months, his left VA was 6/24. This report emphasises the importance of maintaining a high index of suspicion for AK in cases of post-CXL microbial keratitis and highlights the diagnostic value of IVCM, particularly in culture-negative and PCR-negative cases.

Prioritizing Organic Pollutants for Shale Gas Exploitation: Life Cycle Environmental Risk Assessments in China and the US.

Environmental impacts associated with shale gas exploitation have been historically underestimated due to neglecting to account for the production or the release of end-of-pipe organic pollutants. Here, we assessed the environmental impacts of shale gas production in China and the United States using life cycle assessment. Through data mining, we compiled literature information on organic pollutants in flowback and produced water (FPW), followed by assessments using USEtox to evaluate end-of-pipe risks. Results were incorporated to reveal the life cycle risks associated with shale gas exploitation in both countries. China exhibited higher environmental impacts than the US during the production phase. Substantially different types of organic compounds were observed in the FPW between two countries. Human carcinogenic and ecological toxicity attributed to organics in FPW was 3 orders of magnitude higher than that during the production phase in the US. Conversely, in China, end-of-pipe organics accounted for approximately 52%, 1%, and 47% of the overall human carcinogenic, noncarcinogenic, and ecological impacts, respectively. This may be partially limited by the quantitative data available. While uncertainties exist associated with data availability, our study highlights the significance of integrating impacts from shale gas production to end-of-pipe pollution for comprehensive environmental risk assessments.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

Effect of branched 1,4-butanediol citrate oligomers with different molecular weights on toughness and aging resistance of glycerol plasticized starch.

The thermoplastic starch with glycerol is easy to retrograde and sensitive to hygroscopicity. In this study, branched 1,4-butanediol citrate oligomers with different molecular weights (P1, P2, and P3) are synthesized, and then mixed with glycerol (G) as the co-plasticizers to prepare thermoplastic starch (CS/PG). The results show that the molecular weight and branching degree of the branched 1,4-butanediol citrate oligomers increase as reaction time prolongs. Compared with glycerol plasticized starch, the thermoplastic starch films with branched 1,4-butanediol citrate oligomers/glycerol (10 wt%/20 wt%) have a better toughness, transmittance, and aging resistance, and have a lower crystallinity, hygroscopicity, and thermal stability. The toughness, transmittance, and aging resistance of CS/PG films are positively correlated with the molecular weight of the branched 1,4-butanediol citrate oligomers. These are due to the fact that the branched 1,4-butanediol citrate oligomer with a high molecular weight could form a stronger hydrogen bond and the more stable cross-linked structure with starch chains than that with a lower molecular weight. The elongation at break of CS/P3G film stored for 3 and 30 d are 98.0 % and 88.1 %, respectively. The mixture of branched butanediol citrate oligomers and glycerol, especially P3/G, has a potential application in the preparation of thermoplastic starch.

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma.

PURPOSE: To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL). METHODS: Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed. RESULTS: Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017-24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOAG17V (P = 0.023), and TET2 mutations (P = 0.032). CONCLUSION: EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

A novel exosome-related prognostic risk model for thyroid cancer.

AIM: The aim was to build an exosome-related gene (ERG) risk model for thyroid cancer (TC) patients. METHODS: Note that, 510 TC samples from The Cancer Genome Atlas database and 121 ERGs from the ExoBCD database were obtained. Differential gene expression analysis was performed to get ERGs in TC (TERGs). Functional enrichment analyses including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted on the TERGs. Then we constructed a model based on LASSO Cox regression analysis. Kaplan-Meier survival analysis was applied and a Nomogram model was also built. The immune landscape was evaluated by CIBERSORT. RESULTS: Thirty-eight TERGs were identified and their functions were enriched on 591 GO terms and 30 KEGG pathways. We built a Risk Score model based on FGFR3, ADRA1B, and POSTN. Risk Scores were significantly higher in T4 than in other stages, meanwhile, it didn't significantly differ in genders and TNM N or M classifications. The nomogram model could reliably predict the overall survival of TC patients. The mutation rate of BRAF and expression of cytotoxic T-lymphocyte-associated protein 4 were significantly higher in the high-risk group than in the low-risk group. The risk score was significantly correlated to the immune landscape. CONCLUSION: We built a Risk Score model using FGFR3, ADRA1B, and POSTN which could reliably predict the prognosis of TC patients.

TyG-GGT is a Reliable Non-Invasive Predictor of Advanced Liver Fibrosis in Overweight or Obese Individuals.

BACKGROUND: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. METHOD: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. RESULTS: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. CONCLUSIONS: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group.

Genetic control of DNA methylation is largely shared across European and East Asian populations.

DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.