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Ta-Hsiang Wong,1,2 Cheng-Maw Ho,3,4 Hsao-Hsun Hsu,3,4 Yao-Ming Wu,3,4 Ming-Chih Ho,3,4 Po-Huang Lee,3,4 Rey-Heng Hu3,4 1Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan; 2School of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; 4College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Cheng-Maw Ho, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100, Taiwan, Tel +886-223123456-265914, Email miningho@ntu.edu.twPurpose: Liver transplantation (LT) is the definite curative treatment for hepatocellular carcinoma (HCC), but recurrence can occur even under stringent criteria. “Delayed” HCC recurrence (> 3 years after LT) is not common. Here, we present the clinical features of patients who developed delayed HCC recurrence after LT.Patients and Methods: We reviewed the data of eligible patients from February 1999 to December 2020 from medical records.Results: From among 195 (17%) HCC patients who received LT, 34 experienced HCC recurrence, with 5 (15%) delayed recurrence. These five explant tumors were staged T1b–T2, graded II–III, with two vascular invasion and four beyond the Milan criteria. The median time to recurrence was 6.1 years, with the longest interval being nearly 18 years. Recurrence patterns included two extrahepatic, one intrahepatic, and two mixed extrahepatic and intrahepatic recurrences. A drastic increase in serum alpha-fetoprotein levels was observed in four cases 1 year before recurrence. Management of recurrence included locoregional (surgssical resection in three, radiotherapy in three, transarterial chemoembolization in one, radiofrequency ablation in one) and systemic sorafenib use in three. Two patients died within 12– 18 months, one died within 18– 24 months, and two are still alive until the end of the study, with respective 13.5- and 16.5-month survival.Conclusion: Delayed HCC recurrence could occur over 10 years. Therefore, continual surveillance for recurrence is justified, but biomarkers and intervals or intensities specific for delayed recurrence are not validated, which warrants further validation to facilitate personalized medical care.Keywords: liver transplantation, hepatocellular carcinoma, recurrence, survival, case series

γ-ray flash generation in near-critical-density target irradiated by four symmetrical colliding laser pulses is numerically investigated. With peak intensities about 10^{23} W/cm^{2}, the laser pulses boost electron energy through direct laser acceleration, while pushing them inward with the ponderomotive force. After backscattering with counterpropagating laser, the accelerated electron is trapped in the electromagnetic standing waves or the ponderomotive potential well created by the coherent overlapping of the laser pulses, and emits γ-ray photons in a multiple-laser-scattering regime, where electrons act as a medium transferring energy from the laser to γ rays in the ponderomotive potential valley.

Objective: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms., Methods: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed., Results: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each., Conclusion: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

With the emergence of novel variants, Omicron variant caused a different clinical picture than the previous variants and little evidence was reported regarding perioperative outcomes after Omicron variants. The aim of the study was to evaluate the postoperative outcomes of gastrointestinal cancer patients following Omicron variants infection and also to determine the timing of surgery after infection recovery. A total of 124 patients who underwent gastrointestinal cancer surgery with prior SARS-CoV-2 infection between December 2022 and February 2023 were retrospectively reviewed. 174 cases underwent the same operation during December 2018 and February 2019 as control group. SARS-CoV-2-infected patients were further categorized into three groups based on infected time (1-3 weeks; 4-6 weeks; and ≥ 7 weeks). 90.3% of SARS-CoV-2-infected patients had mild symptoms. The COVID-19 vaccination rate was 71.0%, with a full vaccination rate of 48.4%. There were no significant differences in 30-day morbidity and mortality. There was also no significant difference in pulmonary complications, cardiovascular complications, and surgical complications between the three different diagnosis time groups. In conclusion, reducing waiting time for elective surgery was safe for gastrointestinal cancer patients in the context of an increased transmissibility and milder illness severity with Omicron variant., (© 2024. Italian Society of Surgery (SIC).)

Background: This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI)., Methods: A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses., Results: Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022)., Conclusion: Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Late recurrence of hepatocellular carcinoma after curative resection significantly influences long-term patient survival outcomes, and yet it remains understudied. This study aims to explore the risk factors and patterns of late recurrence and predictors of subsequent outcome., Methods: This single-center retrospective study analyzed 1,701 consecutive patients who achieved a disease-free survival period exceeding 2 years after curative resection for hepatocellular carcinoma between 2001 and 2018. Univariate and multivariate analyses of factors associated with late recurrence and death after recurrence were conducted using Cox's models., Results: The mean age of patients was 60.2 years, with 76.8% being male. During a median follow-up of 8.1 years, 653 patients (38.4%) experienced late recurrence, with median time to recurrence being 4.0 years (interquartile range, 2.7-6.0). Factors such as age >60, chronic hepatitis C, cirrhosis, high albumin-bilirubin grade, absence of family history, multiple tumors, satellite nodules, alpha-fetoprotein levels <400 ng/mL, and minor hepatic resection were identified as risk factors for late recurrence. Among patients with late recurrence, 131 (20.1%) underwent surgical treatment, 272 (41.7%) received radiofrequency ablation, and 27 (4.1%) exhibited extrahepatic lesions. A higher-high albumin-bilirubin grade, recurrent tumor >3 cm, and nonsurgical treatment emerged as predictors of death after late recurrence., Conclusion: Over one-third of patients who remain disease-free for more than 2 years postresection will experience late recurrence during subsequent follow-up. For 2-year disease-free survivors, risk factors for late recurrence differ from early recurrence. Treating underlying hepatitis is of paramount importance, given its association with both the risk of late recurrence and survival outcomes post-recurrence., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction., Method: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models., Result: Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis., Conclusion: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC., (© 2024 Wiley Periodicals LLC.)

Background: Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC)., Methods: Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors., Results: Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33)., Conclusion: Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neural regulation of hepatic metabolism has long been recognized. However, the detailed afferent and efferent innervation of the human liver has not been systematically characterized. This is largely due to the liver's high lipid and pigment contents, causing false-negative (light scattering and absorption) and false-positive (autofluorescence) results in in-depth fluorescence imaging. Here, to avoid the artifacts in three-dimensional (3-D) liver neurohistology, we embed the bleached human liver in the high-refractive-index polymer for tissue clearing and antifade 3-D/Airyscan super-resolution imaging. Importantly, using the paired substance P (SP, sensory marker) and PGP9.5 (pan-neuronal marker) labeling, we detect the sensory nerves in the portal space, featuring the SP + varicosities in the PGP9.5 + nerve bundles/fibers, confirming the afferent liver innervation. Also, using the tyrosine hydroxylase (TH, sympathetic marker) labeling, we identify 1 ) condensed TH + sympathetic nerves in the portal space, 2 ) extension of sympathetic nerves from the portal to the intralobular space, in which the TH + nerve density is 2.6 ± 0.7-fold higher than that of the intralobular space in the human pancreas, and 3 ) the TH + nerve fibers and varicosities contacting the ballooning cells, implicating potential sympathetic influence on hepatocytes with macrovesicular fatty change. Finally, using the vesicular acetylcholine transporter (VAChT, parasympathetic marker), PGP9.5, and CK19 (epithelial marker) labeling with panoramic-to-Airyscan super-resolution imaging, we detect and confirm the parasympathetic innervation of the septal bile duct. Overall, our labeling and 3-D/Airyscan imaging approach reveal the hepatic sensory (afferent) and sympathetic and parasympathetic (efferent) innervation, establishing a clinically related setting for high-resolution 3-D liver neurohistology. NEW & NOTEWORTHY We embed the human liver (vs. pancreas, positive control) in the high-refractive-index polymer for tissue clearing and antifade 3-D/Airyscan super-resolution neurohistology. The pancreas-liver comparison reveals: 1 ) sensory nerves in the hepatoportal space; 2 ) intralobular sympathetic innervation, including the nerve fibers and varicosities contacting the ballooning hepatocytes; and 3 ) parasympathetic innervation of the septal bile duct. Our results highlight the sensitivity and resolving power of 3-D/Airyscan super-resolution imaging in human liver neurohistology.

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote., Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T)., Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital., Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included., Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CR V ) rate was 67.9%, and the cumulative complete hematological response (CR H ) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CR V rate (median time from diagnosis to CR V  = 130 days) and 66.7% CR H rate (median time from diagnosis to CR H  = 218 days). In addition, the VEGF response was less than the partial remission (PR V ) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor., Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

African Swine Fever (ASF), caused by the African swine fever virus (ASFV), has inflicted significant economic losses on the pig industry in China. The key to mitigating its impact lies in accurate screening and strict biosecurity measures. In this regard, the development of colloidal gold immunochromatographic test strips (CGITS) has proven to be an effective method for detecting ASFV antibodies. These test strips are based on the ASFV p30 recombinant protein and corresponding monoclonal antibodies. The design of the test strip incorporates a high-concentration colloidal gold-labeled p30 recombinant protein as the detection sensor, utilizing Staphylococcal Protein A (SPA) as the test line (T line), and p30 monoclonal antibody as the control line (C line). The sensitivity and specificity of the test strip were evaluated after optimizing the labeling concentration, pH, and protein dosage. The research findings revealed that the optimal colloidal gold labeling concentration was 0.05 %, the optimal pH was 8.4, and the optimal protein dosage was 10 μg/mL. Under these conditions, the CGITS demonstrated a detection limit of 1:512 dilution of ASFV standard positive serum, without exhibiting cross-reactivity with antibodies against other viral pathogens. Furthermore, the test strips remained stable for up to 20 days when stored at 50 °C and 4 °C. Comparatively, the CGITS outperformed commercial ELISA kits, displaying a sensitivity of 90.9 % and a specificity of 96.2 %. Subsequently, 108 clinical sera were tested to assess its performance. The data showed that the coincidence rate between the CGITS and ELISA was 93.5 %. In conclusion, the rapid colloidal gold test strip provides an efficient and reliable screening tool for on-site clinical detection of ASF in China. Its accuracy, stability, and simplicity make it a valuable asset in combating the spread of ASF and limiting its impact on the pig industry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The altitudinal gradient pattern of mountain biodiversity and its formation mechanism are hot topics in ecological research. The altitudinal variations of belowground invertebrates are less understood than aboveground plants and animals. With soil mites as the model soil animals, we investigated their distribution patterns from 1318 m to 2500 m above sea level in three mountains of Lyuliang Mountains based on species diversity and functional diversity. We used soil pH, total N, total P, total K, and organic matter content to identify potential drivers of soil mite communities and diversity along the altitudinal gradient. A total of 715 soil mites were collected, belonging to 3 orders, 27 families, 28 genera, and 29 species. Phthiracarus clemens , Geolaelaps praesternalis and Diapterobates humeralis were dominant mites. Non-metric multidimensional scaling showed that soil mites community composition varied significantly among different altitudes due to Epilohmannia ovata predominated in high altitude and P. clemens predominated in middle altitude. There were significant differences in individual density of soil mites among different altitudes. The Margalef, Shannon, and Simpson indices followed a unimodal distribution pattern along the altitudinal gradient. Functional richness and functional evenness showed a unimodal distribution pattern along the altitudinal gradient, while other functional diversity indices changed little with altitude. The RDA results indicated that total K and soil pH were the major drivers for the variations in soil mite communities. The Pielou index of soil mites was significantly positively correlated with soil pH, while functional evenness was negatively correlated with altitude. Individual density, species number, Margalef, Simpson and Shannon indices were significantly positively correlated with functional richness index. Species diversity and functional diversity of soil mites varied differently with altitude. In the future, we should strengthen long-term monitoring and dynamic functional properties of soil mites and the community assembly to deeply understand the relationship between biodiversity and ecosystem functions.

Background: The core principle of HyFlex ('hybrid' and 'flexible') learning is to maintain learning equity under most circumstances. Within a blended framework in precision medical education, how different preferences of synchronous learning environment influence learning process and outcome is limited. We investigated students' preclass online video learning experiences and their choices toward synchronous class formats., Methods: This was a mixed-methods study. During the 2021 academic year, all 5th-year medical students who had viewed online video clips presenting core concepts were asked to complete a survey on their preference for future synchronous class format (face-to-face, online, or HyFlex) and asked to provide reflective comments on their self-learning. Anonymous survey data, online records, and summative assessment scores (short-term learning outcomes) were collected. Kruskal - Wallis or Chi-square tests were used to compare differences between groups, and multiple linear regression was managed to select the factors associated with various choices. The students' comments were coded in a descriptive thematic analysis., Results: Among 152 medical students, 150 responded to the questionnaires, and 109 provided comments. Medical students spent a median of 32 min online, significantly shorter in the face-to-face group than in the online and HyFlex groups. The online group had a lower preclass video completion rate for certain concepts. The choice was not associated with short-term learning outcomes. Student feedback revealed a higher frequency of multiple themes for each student in the face-to-face and HyFlex groups, and these themes fell into the categories of learning efficiency, focus concentration, and course attractiveness., Conclusions: Linking the choice of the class format and learning experiences of preclass online videos sheds light on a step further within a blended framework of precision medical education. Supplement of online interactive elements may help secure learning engagement among students choosing 'online only' class format of HyFlex learning.

Objective: This study aims to investigate the proportion and distribution of female HPB surgeons in China, describe their current status, and analyze the possible barriers and challenges in their careers., Method: Tertiary hospitals with the division of HPB in mainland China in 2021 were enrolled and surgeon demographic information was collected through the review of official websites and/or telephone interviews., Results: The majority of female HPB surgeons (72.92%) were located in the first or second-tier cities in mainland China, with an increasing number of new female HPB surgeons entering the field annually, particularly after 2005 (from 27 to 52 per 5 years). Despite no significant difference in academic backgrounds, female HPB surgeons initiated their careers at an earlier age and took a longer time to obtain chief titles (P < 0.05). Interestingly, female HPB surgeons performed laparoscopic complex HPB cases at a similar rate (95.42%) to their male counterparts and were more likely to specialize in endoscopic surgery (P = 0.021), with a similar ratio of obtaining administrative positions., Conclusion: Minimally invasive surgery may provide females with unprecedented opportunities in the HPB surgery field. However, despite the increasing numbers of female HPB surgeons, the proportion remains low in China., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Phytochemical investigation of the seeds of Coix lacryma-jobi var. lacryma-jobi resulted in the isolation of eight compounds, including two new structures, coixdines A-B ( 1-2 ) and six known compounds ( 3-8 ). The structures of these compounds were determined by 1 D and 2 D NMR spectra referring to the literatures, together with HR-MS analysis. Coixdine A and B are first examples of spermidine skeleton in genus Coix . In the present paper, all compounds were evaluated for the cytotoxicity against two cancer cell lines (CT-26 and BxPC-3) in vitro , and none of the compounds exhibited obvious cytotoxic activity. The present investigation suggests that these amides seem to be of great chemotaxonomic value for C. lacryma-jobi .

Background: The 2022 ASA guidelines recommend the video laryngoscope, video stylet, and flexible videoscope as airway management tools. This study aims to compare the efficacy of three airway devices in intubating patients with difficult airways., Methods: A total of 177 patients were selected and randomized into the following three groups: the video laryngoscope group (Group VL, n = 59), video stylet group (Group VS, n = 59), and flexible videoscope group (Group FV, n = 59). The success rate of the first-pass intubation, time of tracheal intubation, level of glottic exposure, and occurrence of intubation-related adverse events were recorded and analyzed., Results: All patients were successfully intubated with three devices. The first-pass intubation success rate was significantly higher in Groups VS and FV than in Group VL (96.61% vs. 93.22% vs. 83.05%, P < 0.01), but it was similar in the first-pass intubation success rate between Groups VS and FV(P > 0.05). The number of patients categorized as Wilson-Cormack-Lehane grade I-II was fewer in Group VL than in Groups VS and FV (77.97% vs. 98.30% vs. 100%, P = 0.0281). The time to tracheal intubation was significantly longer in Group FV(95.20 ± 4.01) than in Groups VL(44.56 ± 4.42) and VS(26.88 ± 4.51) (P < 0.01). No significant differences were found among the three groups in terms of adverse intubation reactions (P > 0.05)., Conclusions: In patients with difficult airways requiring intubation, use of the video stylet has the advantage of a relatively shorter intubation time, and the flexible videoscope and video stylet yield a higher first-pass intubation success rate and clearer glottic exposure than the use of the video laryngoscope., Trial Registration: Chinese Clinical Trial Registry. No: ChiCTR2200061560, June 29, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Grevillosides R-S ( 1-2 ), two new glucosides of 5-alkylresorcinol derivatives, were isolated from the roots of Ardisia crispa (Thunb.) A. DC. The structures of grevillosides R-S ( 1-2 ) were determined by 1D and 2D NMR, HR-MS, UV, IR experiments and by comparison of their spectroscopic and physical data with literature values. In this paper, grevillosides R-S ( 1-2 ) were tested for their radical-scavenging activity (DPPH and ABTS) and α-glucosidase inhibitory activity in vitro . Grevillosides R-S ( 1-2 ) exhibited weak DPPH radical-scavenging activity with IC 50 values of 72.3 and 485.2 μM, respectively. Grevillosides R-S ( 1-2 ) exhibited no inhibitory activity against α-glucosidase.

Objectives: This meta-analysis aims to evaluate the effect of n-3 polyunsaturated fatty acids (PUFAs) as a part of parenteral nutrition in patients undergoing liver surgery., Design: Systematic review and meta-analysis., Data Sources: PubMed, the Cochrane Central Register of Controlled Trials, Springer link, Web of Science, China National Knowledge Infrastructure and VIP Database., Eligibility Criteria: We included randomised controlled trials (RCTs) and evaluated the outcomes of liver function, inflammatory reaction, the influence of certain markers of the immune system, and specific clinical indexes for patients undergoing liver surgery and receiving parenteral nutrition with n-3 PUFAs., Data Extraction and Synthesis: The Cochrane Collaboration's tool was used to assess the risk of bias for each study. Findings were summarised in Grades of Recommendation, Assessment, Development and Evaluation evidence profiles and synthesised qualitatively., Results: Eight RCTs, including 748 patients (trial: 374; control: 374), were included in the meta-analysis. Compared with patients in the control group, the patients in the n-3 PUFA group who underwent liver surgery had significantly lower aspartate aminotransferase (mean difference, MD -42.72 (95% CI -71.91 to -13.52); p=0.004), alanine aminotransferase (MD -38.90 (95% CI -65.44 to -12.37); p=0.004), white cell count (MD -0.93 (95% CI -1.60 to -0.26); p=0.007) and IL-6 (MD -11.37 (95% CI -14.62 to -8.13); p<0.00001) levels and a higher albumin level (MD 0.42 (95% CI 0.26 to 0.57); p<0.00001). They also had fewer infection complications (OR 0.44 (95% CI 0.28 to 0.68); p=0.0003) and a shorter duration of hospital stay (MD -2.17 (95% CI -3.04 to -1.3); p<0.00001) than the controls. However, there were no significant differences in terms of total bilirubin, TNF-α, IL-2, IgA, IgG, IgM and CD3, biliary leakage and mortality between the two groups., Conclusions: We found that n-3 PUFAs can benefit patients undergoing liver surgery by improving liver function and certain clinical indexes and decreasing related inflammation factors. However, there are limited RCTs on the application of n-3 PUFAs for patients undergoing liver surgery. Further evidence of the benefit of n-3 PUFAs in these patients warrants further exploration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma., Methods: This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed., Results: After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events., Conclusion: In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: There are concerns regarding the adequacy of applying the diagnosis-related groups (DRG) payment system for multiple traumas (i.e., major diagnostic category 24, MDC-24) patients in Taiwan. Therefore, this study used a multi-center dataset to assess the influence of the DRG payment system on the cost and outcome of multiple trauma care., Materials and Methods: We collected data of all multiple trauma patients from the Trauma Registry of three hospitals from 2014 - 2017. Next, we selected patients who met the criteria of MDC-24 and calculated the corresponding DRG payment. Subsequently, we combined the clinical care information with health insurance information to analyze the problems of applying the DRG payment system to multiple trauma care., Results: Overall, of 465 cases, 367 met the criteria of MDC-24, and the mean injury severity score (ISS) was high (average 20.1). The total deficit of the polytrauma DRG cases amounted to 131,445 USD, and the average deficit in each case was 397 USD. In the multivariable analysis, higher revised trauma score and specific lower abbreviated Injury Scale (AIS) scores in certain body regions resulted in profits, while increased length of stay in intensive care units, longer operative time, and higher AIS score in the thorax were significantly correlated with deficits in medical costs., Conclusion: Our study revealed that the current DRG payment system results in financial losses for hospitals. Further, the payment grouping of MDC-24 should consider adding more disease severity factors to reduce the financial constraints faced by trauma centers., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest relevant to this article. No funding was used to support this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This study aimed to evaluate the different outcomes between the non-surgical and surgical groups in patients with major trauma without brain injuries., Methods: This study prospectively collected data from patients with traumatic rib fractures without brain injuries from June 2017 to November 2019. The primary outcomes were the pain score at admission and discharge and the length of hospital stay. We performed multiple regression analysis to compare the outcomes and surgical risk as the severity of chest trauma between both groups., Results: Fifty-three patients were enrolled. There was no statistically significant difference in baseline characteristics between both groups. However, the surgical group had more severe chest trauma than the non-surgical group. After the analysis, the pain score improved significantly in the surgical group. The hospital stay of the surgical group was four days shorter than that of the non-surgical group, and there was severe chest trauma in the surgical group., Conclusions: Surgical management of rib fractures can reduce pain and hospital stay in major trauma patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Better exposition is important for lymph node dissection in the suprapancreatic region and lesser curvature region of the stomach, and digestive tract reconstruction, especially without excellent assistants., Patients and Methods: We developed a new laparoscopic retraction method with the use of two internal retractors (TIRs) punctured along with suture. Clinicopathological data, surgical data, and postoperative outcomes were assessed., Results: Of the 143 patients included, 51 underwent surgery with the double-sling suture method and 92 underwent surgery with the TIRs method. Laparoscopic radical gastrectomy was successfully performed in all patients. There were no significant differences in patient characteristics or preoperative data in the 2 groups. The operative time was significantly shorter in the TIR group, but the amount of bleeding did not differ. No retraction-related complications both in clipped tissue and liver occurred in all patients., Conclusions: Our new retraction technique provided an optimal surgical field and make surgery lower requirements for assistants., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The impact of viral background on long-term effectiveness of different treatment modalities for recurrent hepatocellular carcinoma (HCC) was not fully analyzed., Method: Consecutive 726 patients who developed intrahepatic recurrence after primary hepatectomy for HCC between 2008 and 2015 were retrospectively studied. Post-recurrence survival (PRS) and rerecurrence-free survival (R-RFS) and risk factors were analyzed., Results: After a median follow-up period of 56 months, the 5-year PRS rates of the patients who underwent rehepatectomy, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE) were 79.4%, 83.0%, and 54.6%, respectively. The treatment benefit for PRS was consistently observed in patients with hepatitis B virus (HBV) and non-B, non-C subgroups, but not hepatitis C virus (HCV). For patients with late recurrence of HCC, R-RFS was superior in HBV subgroup and HCV subgroup which received antiviral treatment (compared to naïve HCV subgroup). Survival difference triaged by viral status was lost in the counterpart with early recurrence. Overall, RFA improved PRS and R-RFS in patients receiving antiviral treatment., Conclusion: To achieve long-term survival after HCC recurrence, rehepatectomy and RFA were comparably effective, particularly among those with HBV. Antiviral treatment complemented survivals of patients with HCV after RFA, particularly in late first recurrence., (© 2023. The Society for Surgery of the Alimentary Tract.)

Introduction: A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely, the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform., Methods: A total of 153 HBV-HCCs after surgical resection were subjected to capture sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC., Results: They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate, and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort., Conclusion: A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies., Competing Interests: P.J.C. is the consultant and received a grant from TCM Biotech. S.T.T., C.F.H., and Y.C.W. are employees of TCM Biotech., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Our objective was to compare the value of positron emission tomography/magnetic resonance imaging (PET/MRI) with the new imaging agent [ 68 Ga]Ga-DOTA-FAPI-04 and the traditional imaging agent [ 18 F]FDG for the preoperative diagnosis of gastric cancer., Methods: Forty patients with gastric cancer diagnosed by gastroscopy in gastrointestinal surgery at our hospital from June 2020 to January 2021 were analyzed. All patients underwent simultaneous [ 68 Ga]Ga-DOTA-FAPI-04 and [ 18 F]FDG PET/MRI. The standard uptake value (SUV), fat removal standard uptake value (SUL), and diagnostic sensitivity, specificity, and accuracy for primary and metastatic lesions were compared, and their diagnostic value for different lymph node dissection stages was analyzed., Results: The median age of the patients in this cohort was 68 years. Twenty-nine patients underwent surgery, and 11 patients underwent gastroscopic biopsy. The SUV max of primary lesions in the FDG group and the FAPI group was 5.74 ± 5.09 and 8.06 ± 4.88, respectively ( P < 0.01); SUL max values were 3.52 ± 2.80 and 5.64 ± 3.25, respectively ( P < 0.01). The SUV max of metastases in the two groups was 3.81 ± 3.08 and 5.17 ± 2.80, respectively ( P < 0.05). The diagnostic sensitivities for primary lesions in the FDG group and the FAPI group were 0.72 and 0.94, respectively ( P < 0.05). Combined with postoperative pathological staging, there was no difference in diagnostic sensitivity and specificity of lymph node staging between the FDG and FAPI groups ( P > 0.05)., Conclusion: Compared with the traditional imaging agent, [ 68 Ga]Ga-DOTA-FAPI-04 has better diagnostic efficiency but no substantial advantage for preoperative lymph node staging., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Tao Du et al.)

Background: Optimized conservative treatment of rib fractures has long been practiced, but surgical fixation has not been promising until recently. We aimed to examine and analyze immediate postoperative outcomes and 6-month quality of life after injury in patients with moderately severe traumatic rib fractures., Methods: We conducted a prospective cohort study between July 2017 and June 2019 at the National Taiwan University Hospital. Seventy-two patients with moderately severe thoracic trauma were enrolled; 38 received conservative treatment and 34 underwent surgical fixation. Quality of life was measured using the 36-item Short Form Survey at; the first 3 days of hospitalization; before discharge; and at 1-, 2-, and 6-month follow-ups (visits 1-5). Baseline characteristics and clinical outcomes were recorded, and linear regression analysis was conducted using the generalized estimating equation., Results: Among patients with moderately severe thoracic injury (chest Abbreviated Injury Scale score≥ 2), the operative group had more severe injuries and longer intensive care unit and in-hospital stays. However, they had a comparable quality of life 6 months after injury and higher physical component scores in the early postoperative period. Linear regression analysis obtained an equation with several factors positively affecting prediction of the mean physical component score, such as body mass index ≤25, age ≤36 years, fewer ribs requiring fixation, and diabetes mellitus. Mental component score did not show an upward trend, but the Work Quality Index largely determined the predicted mean value of the mental component score., Conclusion: Surgical rib fixations hasten recovery in patients with severe thoracic injury (chest Abbreviated Injury Scale ≥3) to achieve 6-month quality of life comparable to patients injured less severely (chest Abbreviated Injury Scale ≥2). The ability to resume previous work positively influenced the mental component score; thus, surgical intervention should also aim to help patients regain their social function., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center., Methods: Survival was retrospectively analyzed., Results: Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P  = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P  = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P  = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P  = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P  = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis., Conclusions: For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Three new terpenoids, ardisiacrispins G-I (1, 4 and 8), and eight known compounds, cyclamiretin A (2), psychotrianoside G (3), 3-hydroxy-β-damascone (5), megastigmane (6), corchoionol C (7), zingiberoside B (9), angelicoidenol (10), trans-linalool-3,6-oxide-β-D-glucopyranoside (11) were isolated from the roots of Ardisia crispa. The chemical structures of all isolated compounds were elucidated by extensive spectroscopic analyses, such as HR-ESI-MS, 1D and 2D NMR spectra. Ardisiacrispin G (1) represents the oleanolic-type scaffold featuring a rare 15,16- epoxy system. All compounds were evaluated for the cytotoxicity against two cancer cell lines (U87 MG and HepG2) in vitro. Compounds 1, 8 and 9 exhibited moderate cytotoxic activity with IC 50 values ranging from 7.6±1.1 to 28.8±3.2 μM., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Laparoscopic colorectal surgery has been proved to have similar oncological outcomes with open surgery. Due to the lack of tactile perception, surgeons may have misjudgments in laparoscopic colorectal surgery. Therefore, the accurate localization of a tumor before surgery is important, especially in the early stages of cancer. Autologous blood was thought a feasible and safe tattooing agent for preoperative endoscopic localization but its benefits remain controversial. We therefore proposed this randomized trial to the accuracy and safety of autogenous blood localization in small, serosa-negative lesion which will be resected by laparoscopic colectomy., Methods: The current study is a single-center, open-label, non-inferiority, randomized controlled trial. Eligible participants would be aged 18-80 years and diagnosed with large lateral spreading tumors that could not be treated endoscopically, malignant polyps treated endoscopically that required additional colorectal resection, and serosa-negative malignant colorectal tumors (≤ cT3). A total of 220 patients would be randomly assigned (1:1) to autologous blood group or intraoperative colonoscopy group. The primary outcome is the localization accuracy. The secondary endpoint is adverse events related to endoscopic tattooing., Discussion: This trial will investigate whether autologous blood marker achieves similar localization accuracy and safety in laparoscopic colorectal surgery compared to intraoperative colonoscopy. If our research hypothesis is statistically proved, the rational introduction of autologous blood tattooing in preoperative colonoscopy can help improve identification of the location of tumors for laparoscopic colorectal cancer surgery, performing an optimal resection, and minimizing unnecessary resections of normal tissues, thereby improving the patient's quality of life. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials., Trial Registration: This study is registered with ClinicalTrials.gov, NCT05597384. Registered 28 October 2022., (© 2023. The Author(s).)

This study aimed to examine the effect of venetoclax coupled with azacytidine in treating older adults with relapsed and refractory (R/R) acute myeloid leukemia (AML). The clinical data of 10 senior patients with AML over 65 years old who were treated with venetoclax and azacytidine, including six patients with R/R AML, were retrospectively evaluated. This study comprised seven males and three females with a median age of 71 years. Five patients had at least one relapse, and one patient did not achieve remission after four cycles of azacytidine monotherapy, considering it resistant. AML with myelodysplasia-related changes was found in four cases. One of the 10 patients died early after 1-13 cycles of venetoclax plus azacytidine treatment due to a protracted period of neutropenia and severe lung infection induced by medications. Six of the remaining nine patients, including six R/R patients, achieved a complete remission (CR) or a CR with incomplete hematologic recovery (CRi). After two cycles of therapy, one patient did not react. Neutropenia lasted an average of 10.5 (6-15) days in all patients, with the most severe cases occurring in the second and third weeks of therapy. Three patients who tested positive for the TP53 gene mutation had the following outcomes: One relapsed patient has been in progression-free remission (PFS) for the past 24 months, whereas another has been in full remission but relapsed 2 months later. Another patient experienced complete remission in myelology for 4 months, but the variable allele fraction (VAF) value steadily rose, suggesting that the illness was on the verge of progressing. IDH2 gene alterations were found in three of four patients who obtained maintained CR for more than 18 months following recurrence. Venetoclax in combination with azacytidine is a successful and well-tolerated therapy for R/R AML in the elderly. Venetoclax and azacytidine may help patients with TP53 mutations and reduce VAF. The IDH2 mutation might be a good predictor of veneclax sensitivity. A notable adverse response in the treatment phase of the regimen is severe infection induced by neutropenia., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To investigate the changes in transplantability between primary and recurrent Hepatocellular carcinoma (HCC) after hepatic resection (HR) and the risk factors for nontransplantable recurrence (NTR)., Methods: Consecutive 3122 patients who received HR for primary HCC between 2001 and 2019 were analyzed for changes in transplantability. Predictors of survival and NTR were evaluated using a competing risk analysis., Results: After a median follow-up of 78.3 months, the 5-year overall survival rate was 82.6%. Also, 58.2% of them developed recurrence after a median of 45.6 months. Recurrence occurred in 1205 and 611 patients with primary transplantable and nontransplantable HCC, respectively, of whom 26.1% and 63.2%, respectively, had NTR. Tumor diameter >3 cm [subdistribution hazard ratios (95% CI), 2.00 (1.62-2.48)], major resection [1.20 (1.00-1.43)], pathological grade >2 [1.28 (1.07-1.52)], microvascular invasion [1.74 (1.45-2.08)], and early recurrence (<1 year) [9.22 (7.83-10.87)] were associated with NTR. The overall transplantable pool increased from 72.3% to 77.5%., Conclusion: Microvascular invasion and early recurrence were risk factors for NTR. Nonetheless, the transplantable pool increased after HR, 41.8% of the patients had no recurrence and may not require liver transplantation. If the patient's liver function is acceptable, HR should be considered the treatment of choice for HCC., Competing Interests: Conflicts of Interest None of the authors have any relevant potential conflicts of interest to disclose., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The injury severity score (ISS) is used in daily practice to evaluate the severity of trauma patients; however, the score is not always consistent with the prognosis. After injury, systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) are related to the prognosis of trauma patients. We aimed to evaluate the associations between the immune response and prognosis in trauma patients. Patients who admitted to the Trauma Intensive Care Unit (ICU) were eligible. Whole blood samples were collected at admission, and then 6, 12, 24, 48 and 72 h after admission. Natural killer (NK) cells, lymphocyte subset population and cytokines release were identified using flow cytometry. We grouped patients by their ISS (≤ 25 and > 25 as very severe injury) and ICU stay (≤ 10 days as a short ICU stay and > 10 days as a long ICU stay) for evaluation. Fifty-three patients were enrolled. ICU stay but not ISS was close correlated with activity daily living (ADL) at discharge. Patients with a long ICU stay had an immediate increase in NK cells followed by lymphopenia which persisted for 48 h. Immediate activation of CD8 + T cells and then exhaustion with a higher programmed cell death-1 (PD-1) expression and suppression of CD4 + T cells with a shift to an anti-inflammatory Th2 phenotype were also observed in the patients with a long ICU stay. When the patients were grouped by ISS, the dynamics of immune responses were inconsistent to those when the patients were grouped by ICU stay. Immune responses are associated with the prognosis of trauma patients, however the currently used clinical parameters may not accurately reflect immune responses. Further investigations are needed to identify accurate predictors of prognosis in trauma patients., (© 2023. The Author(s).)

Background: This study analyzed the respective advantages and disadvantages by comparing volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) on the dose distribution and position verification distribution characteristics in esophageal cancer radiotherapy, in order to provide the reference for the clinical radiotherapy technology optimization of esophageal cancer., Methods: A total of 56 cases of patients with esophageal cancer were selected and applied to the Pinnacle three-dimensional radiation treatment planning system (TPS), in order to design a VMAT plan and IMRT plan under the guidance of image-guided radiotherapy (IGRT). The dosimetry and position verification difference were compared between the two groups., Results: Revealed that the target dose distribution of the VMAT plan and IMRT plan meets the requirements in clinical dosimetry for all 56 patients in this study. Under the premise of similar target coverage, the conformal index (CI) of the VMAT plan, homogeneity index (HI), target volume, BODY-PTV radiated volume and spinal cord D max , bilateral lung V5, V20 and mean lung dose (MLD), monitor unit (MU) and treatment time (TT), as well as position verification and others, were obviously superior to those in the IMRT plan; and the difference was statistically significant., Conclusion: CBCT guided VMAT is a potential effective treatment for esophageal cancer and may be more effective and safer than IMRT., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Gastric cancer is a major public health problem worldwide. Social media has affected public's daily lives in ways no one ever thought possible. Both TikoTok and its Chinese version Douyin are the most popular short video posting platform. This study aimed to evaluate the quality, accuracy, and completeness of videos for gastric cancer on TikTok and Douyin., Methods: The terms "gastric cancer" was searched on TikTok in both English and Japanese, and on Douyin in Chinese. The first 100 videos in three languages (website's default setting) were checked. QUality Evaluation Scoring Tool (QUEST) and DISCERN as the instrument for assessing the quality of the information in each video. Content was analysed under six categories (aetiology, anatomy, symptoms, preventions, treatments, and prognosis). The educational value and completeness were evaluated with a checklist developed by the researchers., Results: A total of 78 videos in English, 63 in Japanese, and 99 in Chinese were analyzed. The types of sources were as follows: 6.4% in English, 4.8% in Japanese, and 57.6% in Chinese for health professionals; 93.6% in English, 95.2% in Japanese, and 3.0% in Chinese for private users; none in English and Japanese, but 39.4% in Chinese for other sources. In all, 20.5% in English, 17.5% in Japanese, and 93.9% in Chinese of videos had useful information about gastric cancer. Among the useful videos, the videos published in Chinese had the highest QUEST(p &lt; 0.05) and DISCERN scores(p &lt; 0.05), followed by those published in Japanese. Among the educational videos, prognosis in English (37.5%), symptoms in Japanese (54.5%), and prevention in Chinese (47.3%) were the most frequently covered topic., Conclusions: TikTok in English and Japanese might not fully meet the gastric cancer information needs of public, but Douyin in Chinese was the opposite., (© 2022. The Author(s).)

Epidermal growth factor receptor (EGFR) is a therapeutic target in nasopharyngeal carcinoma (NPC). The optimal combined modality of optimal combined modality of anti--EGFR monoclonal antibodies, induction chemotherapy (ICT), concurrent chemotherapy and radiotherapy for NPC remains poorly defined. None of previous studies have developed subsequent treatment strategies on the basis of stratification according to the efficacy following ICT plus anti-EGFR mAbs. This study aims to increase treatment intensity for patients with poor efficacy of ICT and reduce treatment toxicity for patients with favourable efficacy of ICT by assessing whether the efficacy of this treatment regimen is non-inferior to ICT plus concurrent chemoradiotherapy (historic controls)., Introduction: METHODS AND ANALYSIS: Pathology-confirmed WHO type II/III NPC patients at clinical stage III-IVA (eighth American Joint Committee on Cancer/Union for International Cancer Control staging system) will be included in the study. They will receive ICT plus nimotuzumab (NTZ), followed by radiotherapy plus NTZ or concurrent chemoradiotherapy plus NTZ (stratified based on the efficacy of ICT plus NTZ). The primary endpoint is 3-year failure-free survival rate; while the secondary endpoints are 3-year overall survival rate, distant metastasis-free survival rate and locoregional recurrence-free survival rate, and short-term remission rate of tumour and treatment toxicity., Ethics and Dissemination: The study protocol has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. Our findings will be disseminated in a peer-reviewed journal. Implementation strategies are in place to ensure privacy and confidentiality of participants., Trial Registration Number: ChiCTR2000041139., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/purpose: Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI., Methods: A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed., Results: A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p < 0.001 and 2.04 ± 1.35 vs. 1.40 ± 1.16, p = 0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival., Conclusion: Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Traditionally, serum CEA and CA19-9 levels are good prognostic factors for gastric cancer. Many gastric cancer patients do not have elevated CEA or CA19-9 levels even at a very advanced stage. This study investigates the significance of the modified Glasgow prognostic score (mGPS) for the survival of gastric cancer patients with normal CEA and CA19-9., Methods: We retrospectively examined 488 curatively resected gastric cancer patients with normal preoperative serum levels of CEA and CA19-9 to evaluate the prognostic ability of mGPS for overall survival. The prognostic significance was analyzed by univariate and multivariate analyses., Results: Age, hemoglobin, white cell count, and neutrophils were each significantly correlated with the mGPS. Multivariate analyses showed that tumor location (HR, 0.803; 95% CI, 0.667-0.966; P =0.020), TNM stage (HR, 2.714; 95% CI, 2.250-3.275; P < 0.001), and mGPS (HR, 1.042; 95% CI, 1.105-1.772; P =0.023) were significantly associated with overall survival. Significant correlations were found between overall survival and mGPS. The Kaplan-Meier analysis demonstrated significant differences among patients with mGPS of 0, 1, and 2 ( P < 0.001), with the mortality rate being higher for patients with a higher mGPS., Conclusion: The mGPS can predict survival in gastric cancer patients with normal CEA and CA19-9., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Shun Zhang et al.)

A laboratory experiment was conducted to investigate the impacts of freeze-thaw intensity (-5-5 ℃, -10-5 ℃) and frequency (1, 5, 10, 15 times) on the community structure of soil arthropod in permafrost zone, Great Hing'an Mountains with the 5 ℃ as control. A total of 4198 individuals of soil arthropod were extracted, belonging to 4 classes, 9 orders, 24 families and 33 genera. The results showed that the number of individuals and groups of soil arthropod decreased significantly in the treatment with high frost intensity (-10-5 ℃), while the individuals of some taxa increased in the treatment with low frost intensity (-5-5 ℃) after the first freeze-thaw incubation. The group number, Margalef index and Shannon index decreased with the increases of freeze-thaw cycling times in low frost intensity treatment, while did not change regularly in high frost intensity treatment. Larva stage was a kind of survival strategy for arthropod to resist low temperature stress, with Acari showing stronger cold tolerance. Different responses of soil arthropod to freeze-thaw cycles, synergistic effect among species and soil environment were factors affecting the structure of soil arthropod community. This study could provide scientific data and theoretical basis for the research and conservation of soil arthropod diversity in the permafrost zone in mid-high latitudes.

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras ( Der m ), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus ( Der p ) and Dermatophagoides farinae ( Der f ). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component ( Der m 1 ). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.

Due to the lack of comprehensive evaluation of all metabolites in wampee, the metabolic reasons for taste differences are unclear. Here, two local varieties YF1 (sweet taste) and YF2 (sweet-sour taste), were selected for quality analysis, followed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based widely targeted metabolomic analysis. YF1 and YF2 were clearly separated by principal component analysis (PCA) and cluster analysis, and 449 metabolites were different between the cultivars, including 29 carbohydrates and 29 organic acids. Among them, d-galactose, d-mannose, and d-fructose 6-phosphate contributed mainly to the sweet taste of the YF1 wampee. l-citramalic acid, 2-hydroxyglutaric acid, and 3-methylmalic acid were the dominant organic acids in YF2 wampee, and therefore, contributed primarily to the sweet-sour taste. The differential metabolites were significantly enriched in the "ascorbate and aldarate metabolism" and "C5-branched dibasic acid metabolism" pathways. Ascorbate played a crucial role in the regulation of sugars and organic acids through those pathways. In addition, high-performance liquid chromatography (HPLC) based quantitative verification exhibited the same specific cultivar variations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Chronic hepatitis B virus (HBV) infection is the major aetiology of hepatocellular carcinoma (HCC). The optimal goal of therapy, hepatitis B surface antigen (HBsAg) loss and anti-HBs production, is achieved rarely and HBsAg-associated HCC risk is well recognized. Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post-liver transplantation or resection, and the implications for therapy. HBV-associated carcinogenesis is a multifactorial process. The observation that HBV-related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg-positive patients post-liver transplantation has been reported in 10%-15% of patients and is likely to be because of expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post-liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV-derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post-surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post-liver transplantation. Use of hepatitis B immunoglobulins that target HBsAg directly, alongside immune-oncology therapies, may be relevant in this setting., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Allergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to Dermatophagoides microceras ( Der m ) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, Dermatophagoides pteronyssinus ( Der p ) and Dermatophagoides farina ( Der f ). However, studies on Der m are scant., Methods: We used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in Der m ( Der m 2 ). We established a Der m 2 -induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP- fve ) isolated from Flammulina veluptipes to evaluate the allergenicity of Der m 2 and the immunomodulatory effects of FIP- fve ., Results: By performing de novo draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid Der m 2 in silico and further confirmed its existence through liquid chromatography-tandem mass spectrometry. Der m 2 is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant Der m 2 by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. Der m 2 elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with Der m 2 , the administration of FIP- fve in either the earlier stage or the late stage, FIP- fve alleviated allergic asthma by moderating airway inflammation and remodeling., Conclusions: Der m 2 induced inflammatory responses in cell and mouse models. FIP- fve alleviated inflammation in Der m 2 -induced asthma in mice by exerting an immunomodulatory effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Wu, Wu, Yu, Ko, Lue and Liu.)

Background: Hepatic stellate cell (HSC) hyperactivation is a central link in liver fibrosis development. HSCs perform aerobic glycolysis to provide energy for their activation. Focal adhesion kinase (FAK) promotes aerobic glycolysis in cancer cells or fibroblasts, while FAK-related non-kinase (FRNK) inhibits FAK phosphorylation and biological functions., Aim: To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs., Methods: Mouse liver fibrosis models were established by administering CCl 4 , and the effect of FRNK on the degree of liver fibrosis in the model was evaluated. Transforming growth factor-β1 was used to activate LX-2 cells. Tyrosine phosphorylation at position 397 (pY397-FAK) was detected to identify activated FAK, and the expression of the glycolysis-related proteins monocarboxylate transporter 1 (MCT-1) and enolase1 (ENO1) was assessed. Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region, which were validated with chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays., Results: The pY397-FAK level was increased in human fibrotic liver tissue. FRNK knockout promoted liver fibrosis in mouse models. It also increased the activation, migration, proliferation and aerobic glycolysis of primary hepatic stellate cells (pHSCs) but inhibited pHSC apoptosis. Nevertheless, opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells. Mechanistically, the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis, which was inhibited by exogenous FRNK., Conclusion: FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway, thereby improving liver fibrosis. FRNK might be a potential target for liver fibrosis treatment., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The aim of the study was to investigate clinical evidence for defining the indications of prophylactic level IB radiotherapy (RT) in nasopharyngeal carcinoma (NPC)., Methods: We conducted a phase 2 prospective study in 116 newly diagnosed patients with NPC treated by intensity-modulated RT. Whether level IB was irradiated is based on the risk score model (RSM). Two groups based on RSM were obtained: low risk and high risk. Omission of level IB irradiation was conducted in the low-risk group, otherwise level IB was contoured as part of the treatment target. Grade 2 or worse xerostomia at 12 months was assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-H&N35 questionnaire., Results: At a median follow-up of 16 months (range, 1-26 months), none of the patients developed failures at level IB. The 1-year overall survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 98.3%, 97.2%, and 95.8%, respectively. At 12 months xerostomia side-effects were reported in 90 of 116 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the low-risk group than in the high-risk group., Conclusion: Omission of level IB irradiation was feasible for patients with low-risk IB lymph nodes metastasis., (© 2022 S. Karger AG, Basel.)

Importance: Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish., Objective: To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations., Design, Setting, and Participants: This cohort study recruited an international group of individuals with ichthyosis and describes characteristic and distinguishing features of common genotypes, including genotype-phenotype associations, during a 10-year period from June 2011 to July 2021. Participants of all ages, races, and ethnicities were included and were enrolled worldwide from referral centers and patient advocacy groups. A questionnaire to assess clinical manifestations was completed by those with a genetic diagnosis., Main Outcomes and Measures: Genetic analysis of saliva or blood DNA, a phenotyping questionnaire, and standardized clinical photographs. Descriptive statistics, such as frequency counts, were used to describe the cases in the cohort. Fisher exact tests identified significant genotype-phenotype associations., Results: Results were reported for 1000 unrelated individuals enrolled from around the world (mean [SD] age, 50.0 [34.0] years; 524 [52.4%] were female, 427 [42.7%] were male, and 49 [4.9%] were not classified); 75% were from the US, 12% from Latin America, 4% from Canada, 3% from Europe, 3% from Asia, 2% from Africa, 1% from the Middle East, and 1% from Australia and New Zealand. A total of 266 novel disease-associated variants in 32 genes were identified among 869 kindreds. Of these, 241 (91%) pathogenic variants were found through multiplex amplicon sequencing and 25 (9%) through exome sequencing. Among the 869 participants with a genetic diagnosis, 304 participants (35%) completed the phenotyping questionnaire. Analysis of clinical manifestations in these 304 individuals revealed that pruritus, hypohydrosis, skin pain, eye problems, skin odor, and skin infections were the most prevalent self-reported features. Genotype-phenotype association analysis revealed that the presence of a collodion membrane at birth (odds ratio [OR], 6.7; 95% CI, 3.0-16.7; P < .001), skin odor (OR, 2.8; 95% CI, 1.1-6.8; P = .02), hearing problems (OR, 2.9; 95% CI, 1.6-5.5; P < .001), eye problems (OR, 3.0; 95% CI, 1.5-6.0; P < .001), and alopecia (OR, 4.6; 95% CI, 2.4-9.0; P < .001) were significantly associated with TGM1 variants compared with other ichthyosis genotypes studied. Skin pain (OR, 6.8; 95% CI, 1.6-61.2; P = .002), odor (OR, 5.7; 95% CI, 2.0-19.7; P < .001), and infections (OR, 3.1; 95% CI, 1.4-7.7; P = .03) were significantly associated with KRT10 pathogenic variants compared with disease-associated variants in other genes that cause ichthyosis. Pathogenic variants were identified in 869 (86.9%) participants. Most of the remaining individuals had unique phenotypes, enabling further genetic discovery., Conclusions and Relevance: This cohort study expands the genotypic and phenotypic spectrum of ichthyosis, establishing associations between clinical manifestations and genotypes. Collectively, the findings may help improve clinical assessment, assist with developing customized management plans, and improve clinical course prognostication.