Search

Jiong-Ze Fang,* Yong Yang,* Hong-Da Zhu, Jian-Nan Sun, Hong-Chao Mi, Cai-De Lu Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cai-De Lu Tel/Fax +86 574- 55835600Email lucaide@nbu.edu.cnObjective: The significance of surgical treatment was analyzed by retrospectively collecting data on the re-resection of intra-abdominal metastases after hepatocellular carcinoma (HCC) surgery in our center over the past 10 years.Methods: The clinical and pathological data of 15 patients who developed intra-abdominal metastases after HCC resection and underwent re-resection from January 2010 to January 2020 were collected to analyze the patients’ characteristics and prognosis.Results: Of the 15 cases of abdominal metastasis, the majority (8 cases) had greater omental metastasis. There were 4 cases of mesenteric metastases, 1 case of abdominal wall metastasis, 1 case of mesenteric plus rectal wall metastasis, and 1 case of colon and mesenteric metastasis. The 1-year, 3-year, and 5-year disease-free survival (DFS) rates were 31.1%, 23.3%, and 11.7%, respectively. The 1-year, 3-year, and 5-year overall survival rates were 93.3%, 28.7%, and 19.1%, respectively. Three patients are currently surviving disease-free, with survival times of 130.4 months, 43.3 months, and 9.4 months, respectively.Conclusion: Although the current guidelines do not recommend surgical resection as the preferred treatment for postoperative abdominal metastases of HCC, surgical resection is recommended for patients with limited or solitary metastasis in the abdominal cavity.Keywords: hepatocellular carcinoma, postoperative recurrence of HCC, intra-abdominal metastasis, disease-free survival, overall survival

Background: The high incidence and mortality of gastric cancer (GC) pose a significant threat to human life and health, and it has become an important public health challenge in China. Body weight loss is a common complication after surgical treatment in patients with GC and is associated with poor prognosis and GC recurrence. However, current attention to postoperative weight change in GC patients remains insufficient, and the descriptions of postoperative weight change and its influencing factors are also different., Aim: To investigate body weight changes in patients with GC within 6 mo after gastrectomy and identify factors that influence dynamic body weight changes., Methods: We conducted a prospective longitudinal study of 121 patients with GC and collected data before (T0) and 1 (T1), 3 (T2), and 6 (T3) mo after gastrectomy using a general data questionnaire, psychological distress thermometer, and body weight measurements. The general estimation equation (GEE) was used to analyze the dynamic trends of body weight changes and factors that influence body weight changes in patients with GC within 6 mo of gastrectomy., Results: The median weight loss at T1, T2, and T3 was 7.29% (2.84%, 9.40%), 11.11% (7.64%, 14.91%), and 14.75% (8.80%, 19.84%), respectively. The GEE results showed that preoperative body mass index (BMI), significant psychological distress, religious beliefs, and sex were risk factors for weight loss in patients with GC within 6 mo after gastrectomy ( P < 0.05). Compared with preoperative low-weight patients, preoperative obese patients were more likely to have weight loss (β = 14.685, P < 0.001). Furthermore, patients with significant psychological distress were more likely to lose weight than those without (β = 2.490, P < 0.001), and religious patients were less likely to lose weight 6 mo after gastrectomy than those without religious beliefs (β = -6.844, P = 0.001). Compared to female patients, male patients were more likely to experience weight loss 6 mo after gastrectomy (β = 4.262, P = 0.038)., Conclusion: Male patients with GC with high preoperative BMI, significant psychological distress, and no religious beliefs are more likely to lose weight after gastrectomy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In a recent Nature elegant study, Wang et al. identified CD300ld, a novel functionally highly conserved tumor immunosuppressive receptor, highly expressed specifically on polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as a key receptor in the regulation of recruitment and immunosuppressive function of PMN-MDSCs. Targeting CD300ld could remodel the tumor immune microenvironment, resulting in a broad-spectrum anti-tumor effect., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods. We found that BmNPV p35 interacts directly with BmVDAC2 rather than BmRACK1. BmNPV infection significantly reduced the expression of BmVDAC2, and activated the mitochondrial apoptosis pathway. Overexpression of BmVDAC2 in BmN cells inhibited BmNPV-induced cytochrome c (cyto c) release, decrease in mitochondrial membrane potential as well as apoptosis. Additionally, the inhibition of cyto c release by BmVDAC2 requires the involvement of BmRACK1 and protein kinase C. Interestingly, overexpression of p35 inhibited cyto c release during mitochondrial apoptosis in a RACK1 and VDAC2-dependent manner. Even the mutant p35, which loses Caspase inhibitory activity, could still bind to VDAC2 and inhibit cyto c release. In summary, our results indicated that BmNPV p35 interacts with the VDAC2-RACK1 complex to regulate apoptosis by inhibiting cyto c release. These findings confirm the interaction between BmVDAC2 and BmRACK1, the interaction between p35 and the VDAC2-RACK1 complex, and a novel target that BmNPV p35 regulates apoptosis in Bombyx mori via interaction with the BmVDAC2-BmRACK1 complex. The result provide an initial exploration of the function of this interaction in the BmNPV-induced mitochondrial apoptosis pathway., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin., Materials and Methods: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events., Results: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death., Conclusion: DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC., Trial Registration: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017., Level of Evidence: 2, Prospective, Non-randomized, Single-arm, study., (© 2024. The Author(s).)

Roots are fundamental for plants to adapt to variable environmental conditions. The development of a robust root system is orchestrated by numerous genetic determinants and, among them, the MADS-box gene ANR1 has garnered substantial attention. Prior research has demonstrated that, in chrysanthemum, CmANR1 positively regulates root system development. Nevertheless, the upstream regulators involved in the CmANR1-mediated regulation of root development remain unidentified. In this study, we successfully identified bric-a-brac, tramtrack and broad (BTB) and transcription adapter putative zinc finger (TAZ) domain protein CmBT1 as the interacting partner of CmANR1 through a yeast-two-hybrid (Y2H) screening library. Furthermore, we validated this physical interaction through bimolecular fluorescence complementation and pull-down assays. Functional assays revealed that CmBT1 exerted a negative influence on root development in chrysanthemum. In both in vitro and in vivo assays, it was evident that CmBT1 mediated the ubiquitination of CmANR1 through the ubiquitin/26S proteasome pathway. This ubiquitination subsequently led to the degradation of the CmANR1 protein and a reduction in the transcription of CmANR1-targeted gene CmPIN2, which was crucial for root development in chrysanthemum. Genetic analysis suggested that CmBT1 modulated root development, at least in part, by regulating the level of CmANR1 protein. Collectively, these findings shed new light on the regulatory role of CmBT1 in degrading CmANR1 through ubiquitination, thereby repressing the expression of its targeted gene and inhibiting root development in chrysanthemum., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Background and Aims: Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC., Methods: A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Pooled effect estimates were calculated using a random effects model within the frequentist framework. Subgroup analyses based on etiology were also conducted., Results: Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included. OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305 [hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.80-1.68] and camrelizumab plus apatinib (HR: 1.06; 95% CI: 0.75-1.51). The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs. The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation. The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages ( R 2 =0.8039, p =0.0155)., Conclusion: This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology., Competing Interests: The authors have no conflict of interests related to this publication.., (© 2024 Authors.)

Objectives: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting., Methods: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy., Results: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively., Conclusions: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC., Clinical Relevance Statement: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events., Key Points: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts., (© 2023. The Author(s).)

Sweet sorghum silage (SS; Sorghum dochna 'Dochna') has been extensively studied in recent years as a supplementary forage-to-corn silage (CS; Zea mays L.), but there are still relatively few studies on its effects on the rumen environment of sheep. Determining the short-term impact of converting roughage from corn straws to SS compared to CS on rumen fermentation and bacterial population dynamics was the main goal of the current study. Twelve female thin-tailed Han sheep (29.8 ± 1.34 kg) were randomly divided into one of two treatments: concentrate supplemented with SS or CS, respectively. During the 15-day pretest period, concentrate was fed in two separate feedings at 0800 h and 1800 h, and ensure that the animals were all consumed within an hour of being fed. Thereafter, the animals had free access to corn straw. The feeding procedures during the pretest period were the same as during the measurement period. Rumen fluid was collected via sheep esophageal tube on the last day of adaptation phase (1-7 days) and stabilisation phase (8-30 days), respectively. The results showed that there was a similarity in the total concentration of VFA (volatile fatty acid) and the proportions of acetate, propionate, butyrate, and branched-chain VFA (P > 0.05) and microbial diversity indices (P > 0.05) between the two silage groups throughout the experimental period. The concentration of Ammonia nitrogen (P = 0.001) and proportion of valerate (P = 0.028) decreased in the CS and SS groups, respectively. The abundance and predicted function of rumen bacteria in the SS group did not differ significantly (P > 0.05) between the two measurement phases. However, the abundance of Prevotella&#95;1 (P = 0.038) was higher in the CS group than in the SS group at 7 d. The abundances of Firmicutes (P = 0.005) and Ruminococcaceae&#95;NK4A214&#95;group (P = 0.002) increased, while the abundances of Bacteroidetes (P = 0.044), Proteobacteria (P = 0.046), and Prevotella&#95;1 (P = 0.009) decreased in the CS group at 30 d. Genes related to pyruvate metabolism (P = 0.020) were significantly higher at 30 d than at 7 d, whereas purine metabolism (P = 0.007), pyrimidine metabolism (P = 0.007), and metabolic pathways (P = 0.010) were lower at 30 d in the CS group. In conclusion, this study indicated that SS maintained a steady rumen environment, while CS caused high fluctuations in bacterial abundance and predicted function for sheep., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

To understand the formation process of typical poisonous plant degraded grassland, we studied the cha-racteristics of vegetation and soil during the gradual expansion of Ligularia virgaurea into the native grassland of Qinghai-Tibet Plateau. The results showed that population density, plant height, coverage, and biomass of L. virgaurea increased during the formation of L. virgaurea degraded grassland. In comparison with native grassland, the degraded grassland had higher total aboveground biomass (113.9%), soil total nitrogen concentration (61.0%), NH 4 + -N (77.9%), organic carbon concentration (45.3%), available phosphorus concentration (78.8%) as well as soil microbial biomass carbon (42.1%) and nitrogen (47.4%), but lower NO 3 - -N (40.1%) and species richness (28.5%) and aboveground biomass (45.7%) of other species beyond L. virgaurea . The extremely strong abilities of interspecific inhibition and morphological plasticity of L. virgaurea , as well as efficient nutrient accumulation and utilization were the keys to its successful expansion, which facilitated the formation of typical L. virgaurea degraded grassland.

Objectives: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT., Material and Methods: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected., Results: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors., Conclusions: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients., Methods: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety., Results: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73)., Conclusion: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line recommendation for intermediate-stage HCC. In real-world clinical practice, TACE also plays an important role in early- and advanced-stage HCC. This review article by the experts from Chinese Liver Cancer Clinical Study Alliance (CHANCE) summarizes the available clinical evidence pertaining to the current application of TACE in patients with early-, intermediate-, and advanced-stage HCC. In addition, combination of TACE with other treatment modalities, especially immunotherapy, is reviewed., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

The reprogramming of host physiology has been considered an essential process for baculovirus propagation. Trehalose, the main sugar in insect blood, plays a crucial role as an instant energy source. Although the trehalose level is modulated following infection with Bombyx mori nucleopolyhedrovirus (BmNPV), the mechanism of trehalose metabolism in response to BmNPV infection is still unclear. In this study, we demonstrated that the trehalose level tended to be lower in BmNPV-infected hemolymph and higher in the midgut. The omics analysis revealed that two trehalose transporters, BmTret1-1 and BmTret1-2, and trehalase, BmTRE1 and BmTRE2, were differentially expressed in the midgut after BmNPV infection. BmTret1-1 and BmTret1-2 had the ability to transport trehalose into the cell and promoted cellular absorption of trehalose. Furthermore, the functions of BmTret1-1, BmTret1-2, BmTRE1 and BmTRE2 in BmNPV infection were analyzed. These genes were upregulated in the midgut after BmNPV infection. Virus amplification analysis revealed that these genes could promote BmNPV proliferation in BmN cells. In addition, these genes could promote the expression of BmPI3K, BmPDK1 and BmAkt and inhibit the expression of BmFoxO in the phosphoinositide 3-kinase (PI3K)-Akt signalling pathway. Similarly, the increased trehalose level in BmN cells could promote the expression of BmPI3K, BmPDK1 and BmAkt and inhibit the expression of BmFoxO. Taken together, BmNPV infection promote the expression of trehalose hydrolysis and transport-related genes. These changes affect the PI3K-Akt signalling pathway to facilitate BmNPV proliferation. These findings help clarify the relationship between trehalose metabolism and BmNPV infection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest exists., (Copyright © 2022. Published by Elsevier Ltd.)

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile., (© 2022. The Author(s).)

Competing Interests: Conflicts of interest: None.

Objectives: To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC)., Methods: In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment-naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety., Results: The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03-9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29-12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173)., Conclusion: TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated., Key Points: • To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: Previous studies have demonstrated that exposed to the initial suboptimal intrauterine environment of gestational diabetes mellitus (GDM) may increase risk of cardiovascular disease in adulthood., Methods: In order to investigate the underlying mechanisms involved in the increased risk of cardiovascular diseases (CVDs) in the offspring of GDM, we applied a high-throughput proteomics approach to compare the proteomic expression profile of human umbilical vessels of normal and GDM offspring., Results: A total of significantly different 100 proteins were identified in umbilical vessels from GDM group compared with normal controls, among which 31 proteins were up-regulated, while 69 proteins were down-regulated. Differentially expressed proteins (DEPs) are validated using Western blotting analysis. The analysis of these differently expressed proteins (DEPs) related diseases and functions results, performed by Ingenuity Pathway Analysis (IPA) software. Based on "Diseases and Disorders" analysis, 17 proteins (ACTA2, ADAR, CBFB, DDAH1, FBN1, FGA, FGB, FGG, GLS, GSTM1, HBB, PGM3, PPP1R13L, S100A8, SLC12A4, TPP2, VCAN) were described to be associated with CVD, especially in Anemia, Thrombus and Myocardial infarction. Functional analysis indicated that DEPs involved in many cardiovascular functions, especially in "vasoconstriction of blood vessel" (related DEPs: ACTA2, DDAH1, FBN1, FGA, FGB, and FGG). Upstream regulator analyses of DEPs identifies STAT3 as inhibitor of ACTA2, FGA, FGB, and FGG., Conclusion: The results of this study indicate that intrauterine hyperglycemia is associated with an elevated risk of cardiovascular risk in the offspring., 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. The handling editor JQ declared a shared parent affiliation with the authors Y-MX and H-TP at the time of review., (Copyright © 2022 Pan, Xiong, Zhu, Shi, Yu, Ding, Xu, Ding, Zhang and Zhang.)

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged ( M (IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ 2 test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)( P <0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P <0.05). There were no significant differences in other baseline data between the two groups(all P> 0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups ( P >0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 ( P =0.009), 9∶4 ( P >0.05) and 4∶9 ( P =0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG ( P< 0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.

Objective To summarize the palliative care consultations proposed by the Emergency Department of Peking Union Medical College Hospital. Methods A retrospective study was conducted on 22 palliative care consultations in the Emergency Department of Peking Union Medical College Hospital from January 2017 to June 2020. Results A total of 18 patients (6 males and 12 females) received palliative care consultations in the Emergency Department,with the average age of (65±8) years (36-88 years).Specifically,10 and 6 patients received once and twice consultations,respectively,and 2 patients did not complete the consultation.Of the patients receiving palliative care consultations,15 had malignant tumors and 3 had non-neoplastic diseases.The reasons for palliative care consultations included communication (61.1%,11/18) and pain relief (61.1%,11/18).In terms of the place of death,8 patients died in the hospital and 6 patients in other medical institutions. Conclusion There is a clear demand for palliative care consultation in the Emergency Department of Peking Union Medical College Hospital,and the consultation can bring help to both emergency doctors and patients.

Ferritin heavy-chain homolog (FerHCH), an iron-binding protein, plays an important role in the host defense against oxidative stress and pathogen infections. In our previous research, Bombyx mori native ferritin had an interaction with B. mori nucleopolyhedrovirus (BmNPV). However, the underlying molecular mechanism of single ferritin homolog responses to BmNPV infection remains unclear. In this study, we found that BmNPV titer and B. mori FerHCH (BmFerHCH) expression were positively correlated with the ferric iron concentration. We performed RNA interference (RNAi) and overexpression experiments to investigate the effects of BmFerHCH on BmNPV proliferation. BmFerHCH knockdown suppressed BmNPV proliferation in vivo and in vitro, whereas BmFerHCH overexpression facilitated BmNPV proliferation. In addition, the oxidative stress level was increased significantly in BmN cells after budded virus infection, while BmFerHCH could neutralize the increased ROS production induced by BmNPV. Of note, we found that ROS was involved in BmNPV-induced apoptosis. Through inhibiting ROS, apoptosis was suppressed by BmFerHCH, whereas BmFerHCH knockdown facilitated apoptosis. Therefore, we hypothesize that BmFerHCH-mediated inhibition of virus-induced apoptosis depends on suppressing ROS accumulation and, thereby, facilitates virus replication. These results suggest that BmFerHCH plays an important role in facilitating BmNPV proliferation and modulating BmFerHCH is potential strategy for studying host-pathogen interactions., (Copyright © 2022. Published by Elsevier B.V.)

Biodegradable stents can degrade step by step and thereby avoid secondary removal by endoscopic procedures in contrast to metal stents. Herein, a biodegradable composite stent, a magnesium (Mg)-based braided stent with a surface coating of poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX), was designed and tested. By adding this drug-loaded polymer coating, the radial force of the stent increased from 33 Newton (N) to 83 N. PTX was continuously released as the stent degraded, and the in vitro cumulative drug release in phosphate-buffered saline for 28 days was 115 ± 13.5 μg/mL at pH = 7.4 and 176 ± 12 μg/mL at pH = 4.0. There was no statistically significant difference in the viability of fibroblasts of stent extracts with different concentration gradients (P > 0.05), while the PTX-loaded stents effectively promoted fibroblast apoptosis. In the animal experiment, the stents were able to maintain esophageal patency during the 3-week follow-up and to reduce the infiltration of inflammatory cells and the amount of fibrous tissue. These results showed that the PTX-PLGA-coated Mg stent has the potential to be a safe and effective approach for benign esophageal stricture. STATEMENT OF SIGNIFICANCE: We designed a biodegradable composite stent, having poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX) coated the surface of the magnesium (Mg)-based braided stent. We evaluated in vitro and in vivo characteristics of the Mg esophageal stent having a PLGA coating plus a variable concentration of PTX in comparison with the absence of PTX PLGA coating. The PTX PLGA stents exerted higher radial force than stents without coating, degraded more quickly in an acid medium, and effectively promoted fibroblast apoptosis in vitro experiments. In a rabbit model of caustic-induced esophageal stricture, there was an increased lumen and decreased inflammation of the esophageal wall in the animals stented with PTX-PLGA versus the sham group, indicating a potential approach for benign esophageal stricture., 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. The authors declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives  During craniotomy for cerebellopontine angle (CPA) lesions, the exact exposure of the margin of the venous sinuses complex remains an essential but risky part of the procedure. Here, we revealed the exact position of the asterion and sinus complex by combining preoperative image information and intraoperative cranial landmarks, and analyzed their clinic-image relationship. Methods  Ninety-four patients who underwent removal of vestibular schwannoma (VS) through retrosigmoid craniotomies were enrolled in the series. To determine the exact location of the sigmoid sinus and the transverse sinus and sigmoid sinus junction (TSSJ), we used preoperative images, such as computed tomography (CT) and/or magnetic resonance imaging (MRI) combined with intraoperative anatomical landmarks. The distance between the asterion and the sigmoid sinus was measured using MRI T1 sequences with gadolinium and/or the CT bone window. Results  In 94 cases of retrosigmoid craniotomies, the asterion lay an average of 12.71 mm on the posterior to the body surface projection to the TSSJ. Intraoperative cranial surface landmarks were used in combination with preoperative image information to identify the distance from the asterion to the sigmoid sinus at the transverse sinus level, allowing for an appropriate initial burr hole (the margin of the TSSJ). Conclusion  By combining intraoperative anatomical landmarks and preoperative image information, the margin of the TSSJ, in particular, the inferior margin of the transverse sinus, can be well and thoroughly identified in the retrosigmoid approach., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Transcatheter arterial chemoembolization (TACE) is the most commonly used method for non-surgical treatment of liver cancer, and it is usually used as an adjuvant therapy in patients who have not developed intrahepatic metastases after surgical resection. Postoperative adjuvant TACE therapy may provide a prognostic benefit in liver cancer patients with high recurrence risk. This article reviews the research progress of adjuvant TACE therapy for liver cancer after radical resection.

Background: Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies., Methods: A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum., Results: Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P<0.05, log 2 |FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes., Conclusion: The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia., (© 2022. The Author(s).)

Background: A national standardized emergency medicine (EM) curriculum for medical students, including specific competencies in procedural skills, are absent in many countries. The development of an intensive simulating training program in EM, based on a tight schedule, is anticipated to enhance the competency of medical students., Methods: A 3-day intensive EM training program, consisting of four procedural skills and 8-hour case-based learning (CBL), was developed by experienced physicians from the EM department in Peking Union Medical College Hospital (PUMCH). Medical students from Peking Union Medical College (PUMC) and Tsinghua University (THU) participated in the training. Three written tests were cautiously designed to examine the short-term (immediately after the program) and long-term (6 months after the program) efficacy of the training. After completion of the training program, an online personal appraisal questionnaire was distributed to the students on WeChat (a mobile messaging App commonly used in China) to achieve anonymous self-evaluation., Results: Ninety-seven out of 101 students completed the intensive training and took all required tests. There was a significant increase in the average score after the intensive simulating training program (pre-training 13.84 vs. 15.57 post-training, P <0.001). Compared with the pre-training test, 63 (64.9%) students made progress. There was no significant difference in scores between the tests taken immediately after the program and 6 months later (15.57±2.22 vs. 15.38±2.37, P =0.157). Students rated a higher score in all diseases and procedural skills, and felt that their learning was fruitful., Conclusions: The introduction of a standardized intensive training program in EM focusing on key competencies can improve clinical confidence, knowledge, and skills of medical students toward the specialty. In addition, having such a program can also enhance student's interest in EM as a career choice which may enhance recruitment into the specialty and workplace planning., Competing Interests: Conflicts of interests: There are no financial or other conflicts of interest related to the submitted article., (Copyright: © World Journal of Emergency Medicine.)

Competing Interests: Conflicts of interest: Authors have no financial or other conflicts of interest related to this submission.

Background: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE., Methods: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the "Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome" study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups., Results: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034)., Conclusion: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events., Competing Interests: Conflicts of interest: The authors declare that they have no competing interests., (Copyright: © World Journal of Emergency Medicine.)

Background: Septic cardiomyopathy (SCM) occurs in the early stage of sepsis and septic shock, which has implications for treatment strategies and prognosis. Additionally, myocardial involvement in the early stages of sepsis is difficult to identify. Here, we assess subclinical myocardial function using laboratory tests and speckle-tracking echocardiography (STE)., Methods: Emergency department patients diagnosed with sepsis or septic shock were included for analysis. Those with other causes of acute or pre-existing cardiac dysfunction were excluded. Transthoracic echocardiography (TTE), including conventional echocardiography and STE, were performed for all patients three hours after initial resuscitation. Samples for laboratory tests were taken around the time of TTE., Results: Left ventricular functions of 60 patients were analyzed, including 21 septic shock patients and 39 sepsis patients. There was no significant difference in global longitudinal strain (GLS), global circumferential strain (GCS), or global radical strain (GRS) between patients with sepsis and septic shock (all with P >0.05). However, GLS and GCS were significantly less negative in patients with abnormal troponin levels or in patients with abnormal left ventricular ejection fraction (LVEF) values (all with P <0.05). There were also moderate correlations between GLS and levels of cTnI ( r =0.40, P =0.002) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) ( r =0.44, P =0.001) in sepsis and septic shock patients., Conclusion: Myocardial dysfunction, e.g., lower LVEF or less negative GLS in patients with sepsis or septic shock, is more affected by myocardial injury. GLS could be incorporated into mainstream clinical practice as a supplementary LVEF parameter, especially for those with elevated troponin levels., Competing Interests: Conflicts of interests: All the authors declare that they have no conflicts of interest., (Copyright: © World Journal of Emergency Medicine.)

Urolithin A (UroA) is a first-in-class natural compound derived from the gut microbiota-derived metabolites of ellagitannins. This research for the first time evaluates the mechanisms of UroA inhibiting advanced glycation end-product (AGE) formation by fluorescence spectroscopy, molecular docking, liquid chromatography (LC) and LC-Oribitrap tandem mass spectrometry. The results indicated that UroA exhibited a good suppression effect on the formation of AGEs in human serum albumin (HSA)-fructose and HSA-methylglyoxal (MGO) systems. Further mechanism analysis revealed that UroA alleviated AGE formation by changing the conformational structure of HSA, trapping reactive MGO to form mono-MGO-UroA complexes, promoting the exposure of chromophores to a more hydrophobic micro-environment, and forming stable UroA-HSA complexes. UroA bound with HSA in an equimolar manner, the binding was an exothermic spontaneous process, subdomain IIIA was the preferred binding pocket, and hydrogen bonding, hydrophobic interactions and van der Waals forces were the major interaction forces. The number of glycation sites detected in glycated HSA was reduced by 1 and 2, respectively, when 181.82 and 363.64 μM UroA was added. These could provide an insight into the mechanism of UroA inhibiting HSA glycation, and highlight its value as a promising glycation inhibitor in the prevention of diabetic complications.

Objective: To investigate the effects and mechanisms of taurine up-regulated gene 1 (TUG1) in hepatic fibrosis. Methods: According to the literature, the classic hepatic fibrosis model of rats induced by 1%DMN(1ml/kg/d) was established. The rats with hepatic fibrosis and activated hepatic stellate cells (HSC) were divided into model control group, negative control group (transfected with siRNA negative control), siRNA interference group (transfected with TUG1). At the end of the experiment, hematoxylin eosin (HE) staining was used to detect the pathological changes of liver tissue; reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to determine the expression levels of α-smooth muscle actin (α-SMA), TUG1, collagen I, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), Smad2 and Smad3 in rat liver tissue and activated hepatic stellate cells. Results: Compared with the model control group, the protein and gene levels of TUG1 and α-SMA in the negative control group were increased significantly( P ＜0.05). The protein and gene levels of TUG1, α-SMA, collagen I, MMP-2, TIMP-1, Smad2 and Smad3 in the liver tissue and activated hepatic stellate cells in the siRNA interference group were decreased ( P ＜0.05) while compared with the blank control group and the negative control group. There were no significant differences in the levels of TUG1, α-SMA, collagen I, MMP-2, TIMP-1, Smad2 and Smad3 in the liver tissue and activated hepatic stellate cells between the control group and the negative control group ( P ＞0.05). Conclusion: TUG1 level is elevated in hepatic fibrosis tissue and activated hepatic stellate cells. Silencing TUG1 may improve the pathological damage of hepatic fibrosis induced by 1% DMN by inhibiting the transforming growth factor(TGF-β1)/ Smad signaling pathway.

Impact of pandemic on the incidence of venous thromboembolism (VTE) in non-COVID-19 patients is undetermined. Thus, a nationwide multicenter retrospective survey was conducted to evaluate the disease burden in non-COVID-19 population. This multi-center survey involved 94 hospitals from 24 provinces in the mainland of China, and collected data on non-COVID-19 patients admitted to the radiology departments due to VTE between January 24 and April 16, 2020. Baseline characteristics, VTE risk factors, clinical manifestations and the treatments were compared with those in the same period of 2019. 3,358 patients with VTE from 74 hospitals were included in this study (1,458 in 2020, 1,900 in 2019). Most aged ≥ 50 years (80.6% in the pandemic, 81.2% in 2019). The number of patients aged 30-39 years increased from 3.9% in 2019 period to 5.8% in the pandemic (p = 0.009). Among the VTE risk factors, the rate of decreased activity increased significantly in the pandemic, and was much higher than that in 2019 (30.7% vs 22.6%, p < 0.0001). Under the risk of decreased activity, patients with comorbidities chronic diseases, especially diabetes, showed significantly a higher incidence of VTE (30.4% vs 22.0%, p < 0.0001). In the pandemic period, fewer patients were treated with anticoagulation alone (33.5% vs 36.7%, p = 0.05), and more underwent inferior vena cava filter (IVCF) implantation, compared with those in 2019 (66.5% vs 63.2%, p = 0.046). The pandemic increased the VTE risk of decreased activity among the non-COVID-19 population. Patients with comorbidities, especially diabetes, have a significant higher risk of VTE during the pandemic., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To explore the degradation, drug release, and mechanical properties of drug-incorporated films made of different ratios of poly(lactic-co-glycolic acid) (PLGA) and different amounts of paclitaxel (PTX), which may serve as the material platform for the manufacturing of biodegradable drug-eluting biliary stents., Materials and Methods: PLGA of different lactic acid/glycolic acid ratios (50/50, 70/30, and 80/20) and 0%, 10, 20, and 30% weight by weight (w/w) PTX was mixed to make PLGA films, which were then cut into small pieces for further testing. Films were immersed in phosphate-buffered saline (pH 7.4) for a maximum of 11 weeks. Samples were taken randomly at Day 2, 4, 6, 8, 10, 12, 14, and weekly thereafter until Week 11 to test tensile strength, weight loss, pH value of the soaking solution, and drug release. The morphology of films was observed using scanning electron microscope (SEM)., Results: At Week 10 of degradation, PLGA 80/20 still withstood a tensile strength of 9.7 newton (N), while PLGA 50/50 and 70/30 cracked spontaneously since Day 4. At Week 11, weight loss of PLGA 50/50, 70/30, and 80/20 was 95.15, 82.32, and 16.17%, respectively; and the lowest pH value of soaking solution was 1.87, 1.95, and 6.58, respectively. Drug release of 10, 20, and 30% PTX groups was 3.52-4.48%, 1.90-2.26%, and 1.44-2.06%, respectively. SEM proved smooth films before degradation; however, after the tensile strength was lost, cracks could be seen., Conclusion: The degradation rate of PLGA can be controlled by altering lactic acid/glycolic acid ratio. Overall, PLGA 50/50 and 70/30 degrade significantly faster than 80/20. PLGA can serve as an effective drug carrier for PTX while being the stent strut, and PTX can be slowly released as PLGA degrades., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Importance: Transarterial chemoembolization (TACE) has been associated with a wide range of practice variations for hepatocellular carcinoma (HCC) between the East and the West. This considerable ambiguity may lead to the heterogeneous quality in treatment and have a negative impact on the role of TACE in the overall multidisciplinary HCC treatment system., Objective: It may be a good start to establish a guideline worldwide to have this consensus from experts who represent east and west, although it does not cover all aspects of TACE., Evidence Review: An international expert panel on TACE is convened to cluster the expert's opinions and summary a standard consensus. This panel committee consist of leading physicians in TACE on HCC from USA, France, Japan, Singapore, Korea, China, and so on. The first-round face-to-face consensus meeting was held during in Nanjing, China in October 2019. The second-round conference for revision of the consensus was held during the Annual Meeting of Chinese College of Interventionalists in August 2020 by a hybrid format of a Webinar and roundtable meeting. After several on-line revisions, the final manuscript was approved by all members of the panel in June 2021., Findings: The consensus statements were organized into the following categories: patients' selection, performing the procedure, TACE outcomes, repeat TACE, TACE failure/refractory, and TACE-based combination treatments., Conclusions and Relevance for Reviews: More and more evidences have showed the better outcomes with strategy of combined TACE with other local therapies such as ablations. The most-recently developing strategy of combined TACE with PD-1/PD-L1 plus tyrosine kinase inhibitor (TKI) agents has shined a light to the HCC patients, especially to those with high risk of tumor recurrence after treatment or TACE failure/refractory., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/hbsn-21-260). The authors report grants from Jiangsu Provincial Special Program of Medical Science (BE2019750), National Natural Science Foundation of China (81827805), and National Key Research and Development Program (2018YFA0704100, 2018YFA0704104)., (2021 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background and Aims: The recognition of transarterial chemoembolization (TACE) failure/refractoriness among Chinese clinicians remains unclear. Using an online survey conducted by the Chinese College of Interventionalists (CCI), the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma (HCC) treatment in clinical practice., Methods: From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting, a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment., Results: A total of 257 clinicians participated and responded to the survey. Most participants agreed that the concept of "TACE failure/refractoriness" has scientific and clinical significance (n=191, 74.3%). Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness (n=88, 46.1%). None of the existing TACE failure/refractoriness definitions were widely accepted by the participants; thus, it is necessary to re-define this concept for the treatment of HCC in China (n=235, 91.4%). Most participants agreed that continuing TACE should be performed for patients with preserved liver function, presenting portal vein tumor thrombosis (n=242, 94.2%) or extrahepatic spread (n=253, 98.4%), after the previous TACE treatment to control intrahepatic lesion(s)., Conclusions: There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions. Further work should be carried out to re-define TACE failure/refractoriness., Competing Interests: The authors have no conflict of interests related to this publication., (© 2021 Authors.)

Background: Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia., Methods: To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS., Results: By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS)., Conclusions: Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers., (© 2021. The Author(s).)

β-1,3-glucan recognition proteins (βGRPs) as pattern recognition receptors (PRRs) play an important role in recognizing various pathogens and trigger complicated signaling pathways in insects. In this study, we identified a Bombyx mori β-1,3-glucan recognition protein gene named BmβGRP4 , which showed differential expression, from a previous transcriptome database. The full-length cDNA sequence was 1244 bp, containing an open reading frame (ORF) of 1128 bp encoding 375 amino acids. BmβGRP4 was strongly expressed in the larval stages and highly expressed in the midgut of B. mori larvae in particular. After BmNPV infection, the expression of BmβGRP4 was reduced significantly in the midgut. Furthermore, a significant increase in the copy number of BmNPV was observed after the knockdown of BmβGRP4 in 5th instar larvae, while the overexpression of BmβGRP4 suppressed the proliferation of BmNPV in BmN cells. Subsequently, the expression analysis of several apoptosis-related genes and observation of the apoptosis morphology demonstrated that overexpression of BmβGRP4 facilitated apoptosis induced by BmNPV in BmN cells. Moreover, BmβGRP4 positively regulated the phosphatase and tensin homolog gene ( BmPTEN ), while expression of the inhibitor of apoptosis gene ( BmIAP ) was negatively regulated by BmβGRP4. Hence, we hypothesize that BmNPV infection might suppress BmPTEN and facilitate BmIAP to inhibit cell apoptosis by downregulating the expression of BmβGRP4 to escape host antiviral defense. Taken together, these results show that BmβGRP4 may play a role in B. mori response to BmNPV infection and lay a foundation for studying its functions.

Objective: To summarize the clinical characteristics and species distribution of nontuberculous mycobacteria(NTM). Methods: We conducted a retrospectively chart review of 453 adult patients with 532 positive cultures with NTM diagnosed and treated in Peking Union Medical College Hospital from January 2014 to December 2018. The information including clinical findings, imaging and etiological data were obtained from clinical examination system. Among these 453 patients, 75 cases met the diagnostic criteria for NTM, with detailed clinical data, culture results and radiological images. Of these patients, 38 were males and 37 were females, with an average age of (50.8±16.2) years. Clinical manifestations, imaging features, NTM species and treatment were analyzed. Results: Among 75 NTM patients, 43 cases (57.3%, 43/75) were infected with Mycobacterium avium Complex (MAC)/intracellular, 18 cases (24.0%, 18/75) with Mycobacterium turtle/abscess, and 7 cases (9.3%, 7/75) with Mycobacterium kansasii. Comorbidities existed in 64.0% patients (48/75). The top two common comorbidities were previous tuberculosis (25.3%, 19/75) infection and clinical bronchiectasis (18.7%, 14/75). After the respiratory disease (82.7%, 62/75), we identified bloodstream as the most frequent manifestation of NTM infection (25.3%, 19/75). MAC was often associated with infection in respiratory system and bloodstream, while rapidly growing mycobacteria (RGM) was more commonly detected in lymph nodes and skin and soft tissues. Cough/expectoration (77.4%, 48/62) was the most common clinical symptom of NTM disease, followed by fever and dyspnea. The frequent imaging findings were nodules (41.9%, 26/62), bronchiectasis (37.1%, 23/62), and fibrous cavities (24.2%, 15/62). In disseminated NTM disease, 94.7% (18/19) patients had underlying diseases and 89.5% (17/19) patients had long-term immunosuppression. Conclusion: The most common NTM species was Mycobacterium avium/intracellular in our series. The predominant infected organ was the respiratory system. Previous tuberculosis history likely increased the risk of infection.

Objective To understand the cognition and related abilities of emergency physicians for palliative care in China. Methods A total of 115 emergency physicians were selected by convenient sampling to conduct a questionnaire survey.The questionnaire included the physicians' basic information,feelings and attitudes towards end-stage patients and their families,cognition of palliative care,and personal ability for palliative care. Results 25.2%,59.1%,and 15.7% of the emergency physicians considered they had "no understanding","partial understanding",and "full understanding" of palliative care,respectively.32(27.8%)physicians participated in palliative care-related lectures and they showed higher self-rated cognition levels( P =0.002).Wechat(39.1%),media(36.5%),and word of mouth(33.0%)were the main ways for emergency physicians to acquire the knowledge of palliative care.Among the emergency physicians,68.7% felt "powerless" in the face of end-stage patients,and 60.9% and 59.1% felt tangled and worried about death causing disputes,respectively.The emergency physicians had low self-rated ability in relieving dyspnea after removal of ventilator[3(2,4)]and eliminating the fear of death[3(3,4)].The self-rated cognition level of emergency physicians to palliative care was positively correlated with most of the self-rated ability indexes. Conclusions Lectures have a significant impact on emergency physicians' cognition level of palliative care.Most of the self-rated indexes of palliative care ability are positively correlated with the cognition level of palliative care.In the face of end-stage patients,most of the emergency physicians are powerless,tangled,and worried about disputes,and their self-rated indexes in relieving dyspnea after removal of ventilator and eliminating the fear of death are low,which necessitates relevant training.

Purpose: To evaluate the current status of women interventional radiologists in China and discuss possible measures to boost their representation in this male-dominated field for a more diverse workplace environment in the future., Materials and Methods: The list of Chinese interventional radiologists obtained from the Chinese College of Interventionalists was retrospectively reviewed. Key information was extracted from the database, including sex, chronologic trends of representation of women interventional radiologists, position, education level, geographic distribution, interventional radiology (IR) practice time, departmental affiliation, and hospital classification., Results: Of the 13,855 entries, 7,324 (52.9%) were interventional radiologists having valid information. Among them, 684 (9.3%) were identified as women. The number of women interventional radiologists has continued to increase since the first woman registered in 1992. The average age of women interventional radiologists was 39.1 years ± 5.7 (range, 26-50). The majority of them were attending physicians (n = 280; 40.9%) with a bachelor's degree (n = 363; 53.1%). Most women interventional radiologists (n = 215, 31.4%) joined this specialty 5-9 years after becoming physicians, whereas 128 (18.7%) started practicing IR from the very beginning. A total of 42.4% of women interventional radiologists were from the departments of IR and cardiology., Conclusions: Although the total number shows an upward trend, women interventional radiologists are still underrepresented. Education level, geographic areas, and other socioeconomic factors may simultaneously influence the population size of women interventional radiologists in China., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Given that the novel coronavirus disease (COVID-19) pandemic has disrupted operations globally, an institution's ability to repeat transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has also been affected. The aim of this study was to evaluate the impact of the COVID-19 on the intervals and outcomes of TACE in HCC patients., Materials and Methods: This retrospective study included 154 HCC patients who underwent follow-up after TACE treatment from January 2020 to March 2020 (n = 71, study group) and January 2019 to March 2019 (n = 83, control group) at two institutions in China. The endpoints included the follow-up interval and overall response rate (ORR). Multivariate logistic regression analyses were performed to identify independent risk factors for a worse ORR. The cut-off point was determined to divide follow-up durations into long- and short-intervals., Results: The median follow-up interval was 82.0 days (IQR, 61-109) in the study group, which was significantly longer than 66.0 days (IQR, 51-94) in the control group ( P = 0.004). The ORR was 23.9 and 39.8% in the study and control group, respectively ( P = 0.037). The cut-off value was 95 days. The grouping (OR, 2.402; 95% CI, 1.040-5.546; P = 0.040), long interval (OR, 2.573; 95% CI, 1.022-6.478; P = 0.045), and China liver cancer staging system (OR, 2.500; 95% CI, 1.797-3.480; P < 0.001) were independent predictors for the efficacy of TACE treatment., Conclusions: The COVID-19 pandemic causes a longer follow-up interval in general, which may further lead to a lower ORR in HCC patients. Those with a follow-up interval of >95 days tend to have a worse prognosis., 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. The reviewer YL declared a shared affiliation, with no collaboration, with several of the authors B-YZ, X-LZ, and C-FN to the handling editor at the time of the review., (Copyright © 2021 Jin, Chen, Zhong, Zhu, Zeng, Li, Guo, He, Deng, Zhu, Ni and Teng.)