Search

Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The transradial approach (TRA) has become popular for diagnostic cerebral angiography. However, this approach is still used less often because of problematic formation of the Simmons catheter. The purpose of this study was to introduce a pigtail catheter exchange technique for Simmons catheter formation to improve the success rates with a shorter operation time and without increasing complications., Methods: This retrospective study included consecutive patients eligible for right TRA cerebral angiography at our institution from 2021. To introduce the technique, the cerebral angiogram of formation of the Simmons catheter in the type II aortic arch was constructed. Patient demographic and angiographic data were collected., Results: In total, 295 cerebral angiographies were evaluated. There were 155 (52.5 %), 83 (28.1 %), 39 (13.2 %), and 18 (6.1 %) patients with types I, II, and III aortic arches and bovine arch, respectively. The total fluoroscopy time, operation time and radiation exposure were 6.3 ± 4.4 min, 17.7 ± 8.3 min and 559.2 ± 197.3 mGy, respectively. The Simmons catheter was successfully formed in 294 of 295 patients, with a success rate of 99.6 %, confirming an effective technique for right TRA cerebral angiography. No severe complications were observed in any patient., Conclusions: Pigtail catheter exchange may be an effective and safe technique for right TRA cerebral angiography. The findings of this report prompted institutions to apply this technique clinically and can serve as a basis for future trials focused on TRA cerebral angiography., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Recently, a state-wide registry identified fracture as a major cause of total hip arthroplasty revision. There were 52.8% of revisions occurring within 6 months (fracture leading cause). Registry sites have a 'surgeon champion' who acts as liaison and advocate. This study evaluated the effect of surgeon volume and role of 'surgeon champion' on fracture rates., Methods: There were 95,948 cases from 2012 to 2019 queried with peri-implant femoral fractures identified (within 6 months). Funnel plots were generated to compare individual surgeon-specific fracture rates. Surgeons who had a fracture rate below the confidence interval were labeled 'green' (lower than mean), within were 'yellow' (no difference), and above were 'red' (significantly higher)., Results: For all surgeons, 19.6% were red, 72.1% yellow, and 8.3% green. There were 17.2% 'surgeon champions' and 6.2% 'nonchampions' that were green (P = .01), while 20.7 and 19.3% were red (P = .82). There was a significant association between volume and performance (P < .01). No surgeons in the lower two quartiles (<84; 84 to 180 cases), while 4 and 29% of higher-volume surgeons (181 to 404; >404 cases) were green. There was no statistical difference in red status by volume (P = .53)., Conclusion: 'Surgeon champions' and high-volume surgeons were more likely to be high performers but not less likely to be low performers. Active involvement in quality improvement and/or high volume was associated with better outcomes but did not impart complication immunity. 'Green' surgeons should mentor colleagues to help reduce fractures by re-evaluating modifiable factors. Analyzing outcomes to promote quality and decrease complications is paramount., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Chronic pancreatitis (CP) is a chronic progressive inflammatory disease of the pancreas, caused by multiple factors and accompanied by irreversible impairment of pancreatic internal and external secretory functions. Pathologically, atrophy of the pancreatic acini, tissue fibrosis or calcification, focal edema, inflammation, and necrosis are observed. Clinical manifestations include recurrent or persistent abdominal pain, diarrhea, emaciation, and diabetes. In addition, CP is prone to develop into pancreatic cancer(PC) due to persistent inflammation and fibrosis. The disease course is prolonged and the clinical prognosis is poor. Currently, clinical treatment of CP is still based on symptomatic treatment and there is a lack of effective etiological treatment. Encouragingly, experiments have shown that a variety of active substances have great potential in the etiological treatment of chronic pancreatitis. In this paper, we will review the pathogenesis of CP, as well as the research progress on anti-inflammatory and anti-fibrotic therapies, which will provide new ideas for the development of subsequent clinical studies and formulation of effective treatment programs, and help prevent CP from developing into pancreatic cancer and reduce the prevalence of PC as much as possible., 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 Li, Liu, Mao, Zheng, Zhang, Zhang, Zhang and Li.)

Background: While total hip arthroplasty (THA) is extremely successful, early failures do occur. The purpose of this study was to determine the cause of revision in specific patient demographic groups at 3 time points to potentially help decrease the revision risk., Methods: Data for cases performed between 2012 and 2018 from a statewide, quality improvement arthroplasty registry were used. The database included 79,205 THA cases and 1,433 revisions with identified etiology (1,584 in total). All revisions performed at <5 years from the primary THA were reviewed. Six groups, men/women, <65, 65-75, and >75 years, were compared at revision time points <6 months, <1 year, and <5 years., Results: There were obvious and significant differences between subgroups based on demographics and time points (P < .0001). Seven hundred and fifty-six (53%) of all revisions occurred within 6 months. The most common etiologies within 6 months (756 revisions) were fracture (316, 41.8%), dislocation/instability (194, 25.7%), and infection (98, 12.9%). At this early time point, the most common revision cause was fracture for all age/gender-stratified groups, ranging from 27.6% in young men to 60% in older women. Joint instability became the leading cause for revision after 1 year in all groups., Conclusion: This quality improvement project demonstrated clinically meaningful differences in the reason for THA revision between gender, age, and time from surgery. Strategies based on these data should be employed by surgeons to minimize the factors that lead to revision., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The relationship between immune and inflammatory responses in hepatocellular carcinoma (HCC) has garnered significant interest. In the peripheral blood and tumour microenvironment (TME), neutrophils, which are innate immune cells, crucially respond to various inflammatory factors, leading to tumour progression. To some extent, they affect the clinical treatment strategy and survival among HCC patients. A high circulating neutrophil-to-lymphocyte ratio is a reliable factor that can be used to predict poor outcomes in HCC patients. However, the mechanisms underlying the protumoural effects of circulating neutrophils remain poorly understood. Besides, the distinct role and function of neutrophils at the site of HCC remain relatively unclear, which is partially attributed to their substantial heterogeneity compared with other immune cells. In this review, we firstly discuss the current information available, detailing distinct subsets, functional phenotypes, and the impact of circulating and tumour-infiltrating neutrophils on tumourigenesis in HCC. Furthermore, we describe recent pre-clinical and clinical studies concerning neutrophils for evaluating the feasibility of targeting diverse protumoural aspects to improve therapeutic efficacy, thus paving the way for neutrophil-based treatment, especially in combination with immunotherapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate how sagittal split ramus osteotomy (SSRO) and Le Fort 1 osteotomy affected the stress distribution of the temporomandibular joint (TMJ) during an anterior teeth bite using the three-dimensional (3D) finite element (FE) method. Fourteen orthognathic surgery patients were examined with mandibular prognathism, facial asymmetry, and mandibular retraction. They underwent Le Fort 1 osteotomy in conjunction with SSRO. In addition, ten asymptomatic subjects were recruited as the control group. The 3D models of the mandible, disc, and maxilla were reconstructed according to cone-beam computed tomography (CBCT). Contact was used to simulate the interaction of the disc-condyle, disc-temporal bone, and upper-lower dentition. Muscle forces and boundary conditions corresponding to the anterior occlusions were applied on the models. The stresses on the articular disc and condyle in the pre-operative group were significantly higher than normal. The contact stress and minimum principal stress in TMJ for patients with temporomandibular disorder (TMD) were abnormally higher. The peak stresses of the TMJ of the patients under anterior occlusions decreased after bimaxillary osteotomy. No postoperative TMD symptoms were found. Maxillofacial deformity led to excessive stress on the TMJ. Bimaxillary osteotomy can partially improve the stress distributions of the TMJ and relieve the symptoms of TMD., (Copyright © 2020 by ASME.)

Context: Fuzheng Huayu recipe (FZHY) combined with entecavir (ETV) is used to treat the cirrhosis caused by chronic hepatitis B (CHB) infection. Objective: To investigate the effect of FZHY on ETV pharmacokinetics under different conditions. Materials and methods: A model of liver fibrosis was created by intraperitoneal injection of dimethylnitrosamine (DMN; 10 μg/kg) for 4 weeks in Wistar rats. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to determine the blood concentration of ETV. Pharmacokinetic characteristics of ETV (0.9 mg/kg) were investigated after co-administration with FZHY (0.55 g/kg) at certain time intervals in normal and model rats. Results: The analytical method for ETV was validated at 0.5-50 μg/L with a correlation coefficient = 0.9996, lower limit of quantitation of 0.5 μg/L and mean accuracy of 104.18 ± 9.46%. Compared with the ETV-N group, the pharmacokinetic parameters of the EF-2 group did not change significantly, but that of the EF-0 group decreased in C max to 27.38 μg/L, in AUC 0- t from 323.84 to 236.67 μg/h/L, and a delay in T max from 0.75 to 6.00 h; that of the EF-0 group presented a decrease in C max of 61.92%, delay in t 1/2 of 2.45 h and delay in T max of 2.92 h. The t 1/2e and V d / F of ETV were increased significantly to 8.01 h and 24.38 L/kg in the ETV-M group. Conclusions: The effects of FZHY on ETV pharmacokinetics were diminished with an increase of interval time. The best time to administer both drugs is >2 h apart.

Objective: The aim of this study is to investigate the predisposing factors and the effect of healthy education on recurrence of vestibular migraine (VM), so as to provide a scientific basis for increasing the knowledge rate and reducing the recurrence rate of VM patients. Method: Questionnaires, memory diary, regular follow-up, etc. were used to understand the possible predisposing factors of VM patients. Self-assessment depression scale (SDS) and self-assessment anxiety scale (SAS) were used to evaluate patients' mental and psychological status, and visual analogue scale (VAS) was used to evaluate the severity of vertigo. Health education was conducted for VM patients through face-to-face consultation, material distribution, modern multimedia and other methods. The knowledge rate, anxiety and fear psychological state, recurrence frequency of vertigo, duration and severity of vertigo were compared before and after the healthy education. Result: Of 103 cases of the object of study, 100 patients (97.1%) with different degree of sleep disorders, 96 cases (93.2%) had a clear family history with vertigo or dizziness headache, 90 cases (87.4%) had history of motion sickness, 90 cases (87.4%) had confined space history of intolerance, 82 cases (79.6%), recurrent cause psychological anxiety, fear, 80 cases (77.7%), lack of exercise, 79 cases (76.7%) under pressure from life or work, 53 (51.5%) had food preference, 8 cases (7.8%) think much rain attacks more frequent when humid climate,seven (6.8%) reported more episodes during the spring or spring/summer exchanges.After health education, patients were followed up for 6 months to 2 years with a median of 15 months, and their knowledge rate of VM was increased from 12.6% (13 cases) to 98% (101 cases).The psychological ratio of anxiety and fear decreased from 79.6% (82 cases) to 7.8% (8 cases).The SAS score decreased from 47.9±4.4 to 45.5±4.2, and the SDS score decreased from 39.7±3.6 to 38.2±3.8.The unhealthy lifestyle and eating habits （lack of exercise, stress, and eating preferences at least 1 item）decreased from 89.4% (92 cases) to 32.1% (33 cases).The recurrence rate of 83.5% (86 cases) of the patients was reduced by 1 time or more, and the rate of no recurrence increased from 1% (1 case) to 15.5% (16 cases) within half a year.The duration of the attack was reduced by 20% or more in 48.5%(50 cases),The mean duration of the attack declined from (17.4±1.4) hours before healthy education to (10.5±0.9) hours after healthy education.The VAS score of 86.4%(89 cases) with recurrence severity decreased by 2 points or more. The average VAS score before and after education was (6.6±0.1) points and (4.5±0.1) points respectively.The above differences were statistically significant ( P <0.01) compared with those before and after education. Conclusion: Sleep disorder, airtight space intolerance, excessive stress, lack of exercise, and dietary preference may be related factors to trigger VM attacks. Healthy education can significantly improve the awareness of VMs, and promote patients to change their lifestyle and eating habits. It can significantly improve patients' anxiety and fear psychological state, reduce the frequency of attack, shorten the duration of attack, and reduce the severity of selfassessment, which is worthy of clinical promotion., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer. Therefore, a recombinant DNA plasmid expressing the three exogenous genes, VP3 , IL-18 and hemagglutinin neuraminidase ( HN ), was constructed. Flow cytometry, acridine orange/ethidium bromide staining and analysis of caspase-3 activity were performed in H22 cell lines transfected with the recombinant DNA plasmid. In addition, 6-week-old C57BL/6 mice were used to establish a H22 hepatoma-bearing mouse model. Mice tumor tissue was analyzed by immunohistochemistry and scanning electron microscopy. The results of the present study revealed that the recombinant DNA vaccine containing the VP3 , IL-18 and HN genes inhibited cell proliferation and induced autophagy via the mitochondrial pathway in vivo and in vitro .

Aim: Genetic analysis has revealed a subset of recurrently mutated genes and aberrant cellular signaling pathways in hepatocellular carcinoma. To investigate genetic alterations and dysregulated pathways in hepatocellular carcinoma, we performed targeted sequencing and exome analysis using next-generation sequencer., Methods: We analyzed the somatic mutational profiles of 16 genes in primary hepatocellular carcinoma by targeted ultra-deep sequencing using nine pairs of specimens (tumor and peripheral blood) and whole-exome sequencing using one pair of samples., Results: Overall, somatic mutations with high allele fraction were identified in tumor tissues by targeted deep sequencing. Somatic mutations with high allele fraction were observed in TP53 (3/9; 33%) and CTNNB1 (2/9; 22%) genes in five out of nine (55%) specimens. In vitro analysis showed that CTNNB1 H36P mutant protein identified in tumor samples was resistant to protein degradation and promoted cell proliferation. Exome sequencing identified SLIT3 mutation, implying that dysregulation of axon guidance genes is involved in the development of hepatocellular carcinoma. These results showed that TP53 and WNT/β-catenin signaling pathways were commonly mutated in hepatocellular carcinoma., Conclusion: These results suggest that targeted sequencing and exome sequencing enable the identification of putative oncogenic driver mutations during the development of hepatocarcinoma., (© 2016 The Japan Society of Hepatology.)

Objective: To investigate the measurement effect of droplet digital PCR(dd-PCR) for H.pylori infections in chronic tonsillitis and explore the correlations between H.pylori infections and chronic tonsillitis. Method: The subjects consisted of 48 chronic tonsillitis patients aged between 7 and 52 years scheduled for tonsillectomy.Core biopsy samples from resected tonsillary tissue was tested for H.pylori detection using both RT-PCR and dd-PCR for the CagA and VacA genes.Preoperative patient venous blood samples were also tested for H.pylori antibodies by Enzyme-linked immunosorbent assay(ELISA).ELISA,RT-PCR and dd-PCR were also used to detect expression of CagA and VacA genes in plasma and tissue of 30 cases of obstructive sleep apnea syndrome(OSAHS) and 35 cases of plasma from healthy subjects. Result: The expression of H.pylori antibodies is tested in plasma:48 chronic tonsillitis patients(10.12±3.23)ng/ml, OSAS(9.87±2.43)ng/ml, healthy subjects(9.34±3.38) ng/ml.There was no significant difference between groups in the plasma.The VacA and CagA gene sequences were detected by RT-PCR:48 chronic tonsillitis patients VacA(27.1%),CagA(16.7%),VacA+CagA(16.7%);30 OSAHS,VacA(23.3%),CagA(20.0%),VacA+CagA(16.7%);all of which were also positive by dd-PCR,thus were considered H.pylori infected.Moreover,The expression of VacA and CagA increased in tissues testing by dd-PCR:48 chronic tonsillitis patients VacA(72.9%),CagA(52.1%),VacA+CagA(39.6%);30 OSAHS,VacA(33.3%),CagA(23.3%),VacA+CagA(16.7%). Conclusion: Our study supports the possible role of H.pylori in chronic tonsillitis.H.pylori maybe one of the risk factors of chronic tonsillitis.dd PCR had bettersensitivity and specificity compare to H.pylori serological and RT PCR.Feasible anti H.pylori treatment maybe used for H.pylori associated chronic tonsillitis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Hepatocellular carcinoma is one of the deadliest types of cancer. Despite improvements in treatment over the past few decades, patient survival remains poor and there is an urgent need for development of targeted therapies. MicroRNAs represent a class of small RNAs, frequently deregulated in human malignancies. We are reviewing the role of microRNA in the development of primary hepatocellular carcinoma and its use as a biomarker for early diagnosis and clinical treatment. First, we describe the current incidence and possible causes of the incidence of hepatocellular carcinoma, followed by the introduction of microRNA synthesis, maturation and function, and finally we explain the role of microRNA in the development of hepatocellular carcinoma and its clinical value as a biological marker in the diagnosis and treatment of liver cancer. A comprehensive analysis of cellular microRNA is a benefit for early diagnosis of hepatocellular carcinoma and early clinical intervention, and microRNA is considered by some to be a key target of gene therapy to control the occurrence and development of hepatocellular carcinoma..

A total of 1502 samples, including feces of sheep (793) and cattle (348), pasture soil (118), dung compost (147) and barn soil (96), were examined between October 2012 and August 2014 to discover potential strains of nematophagous fungi for the biological control of livestock-parasitic nematodes. These samples were collected from 87 sites located in 48 counties of 20 provinces (autonomous regions/municipalities) of China. Fungi were identified down to a species level. Four hundred and seventy-seven isolates, which were distributed in 8 genera and 28 taxa, were identified as nematophagous fungi. Nematode-trapping fungi included 17 species and one unidentified species of Arthrobotrys, two of Dactylella, Drechslerella dactyloides, and Duddingtonia flagrans. Five identified species and two unidentified species of endoparasitic fungi were isolated. The predominant species from all regions were Arthrobotrys oligospora, followed by Arthrobotrys musiformis, Arthrobotrys (Monacrosporium) thaumasiun, and Arthrobotrys (Monacrosporium) microscaphoides. Species with adhesive networks were the most frequently isolated. Among the endoparasitic fungi, Podocrella harposporifera (Harposporium anguillulae) was the most common species, followed by Harposporium lilliputanum and Harposporium arcuatum. Based on Shannon diversity index, the diversity levels of nematophagous fungi were relatively higher in samples associated with cattle, barn soil, and subtropical monsoon climate zone. Three species isolated from this study, namely, Duddingtonia flagrans, Arthrobotrys salina (Monacrosporium salinum), and Arthrobotrys oligospora var. sarmatica, are newly recorded in China, and 20 species (including one unidentified species) are newly recorded in sheep and cattle barn soils worldwide., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nematophagous fungi are considered to have the best potential as biological agents for the control of gastrointestinal nematodes in domestic animals. However, relatively few studies have been conducted with the genus Monacrosporium, especially with strains native to China. In the present study, we isolated and identified nematophagous fungi from fresh sheep feces. A pure fungal strain was molecularly characterized, and its nematophagous activity was evaluated. The morphological plasticity of the isolated strain, as well as its interaction with the nematode targets, was observed by scanning electron microscopy of the infected Trichostrongylus colubriformis L3 and the free-living nematode Caenorhabditis elegans. Three isolated fungal strains from the 30 fresh fecal samples of sheep from Inner Mongolia, China exhibited predatory activity; however, only a single strain was successfully purified (SF 0459). The SF 0459 strain was characterized by morphological analysis of its conidia and sequencing of its ITS1-5.8S rDNA-ITS2 region. This strain was identified to be Monacrosporium salinum (GenBank ID: KP036623). Nematophagous fungus helper bacteria were found at the interaction points between fungi and nematodes. The percentage of live T. colubriformis L3 was reduced by 83.79-88.69% based on the in vitro assay., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ethnopharmacological Relevance: Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis., Aim of the Study: To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY., Materials and Methods: Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats., Results: A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (P<0.05). Tissue distribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (P<0.05). Meanwhile, the result also reveals that the hepatic fibrosis could delay the peak time of lignans in liver., Conclusion: The results proved that the established UHPLC-MS/MS method could be applied to the comparative study on pharmacokinetics and tissue distribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To provide a scientific basis for quality control of "Boju" Chrysanthemum morifolium by establishing a HPLC characteristic fingerprint., Methods: The HPLC analysis was performed on a Spursil C18 chromatographic column (250 mm x 4. 6 mm, 5 µm), and the mobile phase was acetonitrile-0. 1% phosphoric acid in a gradient mode with the flow rate of 1. 0 mL/min. The detection wavelength was 325 nm and the temperature of column was 30 °C., Results: The common pattern of HPLC characteristic chromatographic profile was established. There were 16 common peaks, five of which were identified in the pattern. The similarities of 10 batches of "Boju" Chrysanthemum monrfolium were evaluated, and all of them were greater than 0. 900., Conclusion: This analysis method of HPLC characteristic chromatographic fingerprint is simple and reproducible, and it can provide a scientific basis for identification and quality evaluation of "Boju" Chrysanthemum monfolium.

To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.

Lenvatinib, an approved first-line regimen, has been widely applied in hepatocellular carcinoma (HCC). However, clinical response towards Lenvatinib was limited, emphasizing the importance of understanding the underlying mechanism of its resistance. Herein, we employed integrated bioinformatic analysis to identify calpain-2 (CAPN2) as a novel key regulator for Lenvatinib resistance in HCC, and its expression greatly increased in both Lenvatinib-resistant HCC cell lines and clinical samples. Further in vitro and in vivo experiments indicated that knocking down CAPN2 greatly sensitized HCC cells to Lenvatinib treatment, while overexpression of CAPN2 achieved opposite effects in a Lenvatinib-sensitive HCC cell line. Interestingly, we observed a close relationship between CAPN2 expression and cancer stem cell (CSC) traits in HCC cells, evidenced by impaired sphere-forming and CSC-related marker expressions after CAPN2 knockdown, and verse vice. Mechanistically, we strikingly discovered that CAPN2 exerted its function by both enzyme-dependent and enzyme-independent manner simultaneously: activating β-Catenin signaling through its enzyme activity, and preventing GLI1/GLI2 degradation through direct binding to YWHAE in an enzyme-independent manner, which disrupting the association between YWHAE and GLI1/GLI2 to inhibit YWHAE-induced degradation of GLIs. Notably, further co-immunoprecipitation assays revealed that YWHAE could promote the protein stability of CAPN2 via recruiting a deubiquitinase COPS5 to prevent ubiquitination-induced degradation of CAPN2. In summary, our data demonstrated that CAPN2 promoted Lenvatinib resistance via both catalytic activity-dependent and -independent approaches. Reducing CAPN2 protein rather than inhibiting its activity might be a promising strategy to improve Lenvatinib treatment efficiency in HCC. [ABSTRACT FROM AUTHOR]

Objective: Acute radiation enteritis is one of the most common complications of radiotherapy for patients with cervical cancer. This study aims to investigate the effect of acute radiation enteritis on the prognosis of patients with cervical cancer receiving radiotherapy and to establish a nomogram predicting the patients' overall survival (OS). Methods: The clinical data of 288 patients with cervical cancer who were admitted to our department from 2014 to 2020 were retrospectively analyzed, and the survival of patients were followed up. The Kaplan-Meier method was used to calculate the survival rate and for univariate analysis, and the Cox regression model was used for multivariate prognostic analysis. A nomogram survival prediction model was established based on independent risk factors, and the concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive accuracy of the model. The clinical applicability of the model was assessed by the decision curve. External validation of the nomogram prediction model was performed in 74 patients admitted to our hospital from 2020 to 2021. Results: 60 patients (20.8%) developed grade 2 or higher acute radiation enteritis. The 1-, 3-, and 5-year OS rates were 94.4%, 80.9%, and 77.4%, respectively. Multivariate Cox regression analysis showed that: Age ≥ 60 years, diabetes/hypertension, anemia, FIGO stage III-IV, poor differentiation, pelvic lymph node metastasis, NLR ≥ 2.54 and grade 2 or higher acute radiation enteritis were independent risk factors for OS in cervical cancer patients undergoing radiotherapy (P < 0.05). The C-index of OS nomogram model was 0.815 (95% CI: 0.766-0.864). The AUC of 3-year and 5-year OS were 0.849 (95%CI: 0.789-0.909) and 0.840 (95%CI: 0.782-0.899), respectively. The AUC value of 3-year OS in the external validation set was 0.779 (95%CI: 0.635-0.922). The calibration curve showed that the model was well calibrated, and the decision curve verified the clinical applicability of the constructed nomogram. Conclusion: This study established an accurate predicting nomogram based on independent prognostic factors in cervical cancer patients receiving radiotherapy, and patients with grade 2 or higher acute radiation enteritis should be paid more attention to in clinical practice. [ABSTRACT FROM AUTHOR]

High‐producing dairy cows are susceptible to altered redox balance owing to their high secretion and strong metabolism during transition to lactation. Previously reports demonstrated that pterostilbene (PTE) alleviate hydrogen peroxide (H2O2)-induced oxidative damage. However, molecular mechanism underlying protective role of PTE in H2O2-elicited oxidative stress in bovine mammary epithelial cells (MAC-T cells) remains unclear. The aims of our research is to clarify the potential molecular mechanisms of PTE in H2O2-triggered oxidative damage. MAC-T cells were pre-treated with PTE (0, 10, 25 and 50 μM) for 12 h and then cultured with H2O2 (0, 100, 200, 400, 600, 800 and 1000 μM) for another 24 h. The results were interpreted by CCK8, western blot, and immunofluorescence assay. Results showed that PTE significantly attenuated H2O2-mediated reduction in T-AOC, SOD and GSH-Px activity. Mechanistic studies found that PTE restricted the H2O2-induced protein expression of HO-1, GPX4 and SOD1, and PTE reversed intracellular MDA and ROS generation and decreased the MMP in MAC-T cells. Moreover, H2O2 exposure markedly inhibited mitophagy, whereas PTE pre-treatment activated PINK1/Parkin-mediated mitophagy pathway, which further limited ROS production. Overall, PTE can be used to improve oxidative stress and as a novel antioxidant agent in dairy cows. Highlights: PTE restored the levels of H2O2-induced oxidative stress markers (T-AOC, SOD, GSH-Px and MDA) in MAC-T cells. PTE effectively blocked the increase of protein expression (HO-1, SOD1 and GPX4) in H2O2-induced MAC-T cells. PTE remarkably decreased the accumulation of ROS and improved MMP in H2O2-induced MAC-T cells. PTE exerted a significant protective effect against oxidative stress injury by reducing the inhibition of H2O2 on mitophagy. [ABSTRACT FROM AUTHOR]

The work presented is a comprehensive review of the role of the human microbiota in the context of the COVID-19 pandemic. A diverse microbial community heavily colonizes the human body called the microbiota, with the gut microbiota being the most diverse. The composition of the microbiota varies in different parts of the body and changes with age, diet, and other environmental factors. Emerging evidence suggests that the gut microbiota plays a critical role in modulating the host immune response and may influence the severity of COVID-19. Patients with COVID-19 have significant alterations in their gut and respiratory microbiota, characterized by a depletion of beneficial commensal bacteria and an enrichment of opportunistic pathogens. These changes in microbiota composition are associated with elevated inflammatory markers, a dysregulated immune response, and more severe disease outcomes. In addition, changes in the gut microbiota can affect lung and brain function, influencing the severity of COVID-19 cases and neurological symptoms, as well as long-term neurological complications associated with the disease. Due to the importance of the microbiota in COVID-19, several therapeutic approaches targeting the microbiota have been proposed to improve outcomes in this disease, including fecal microbiota transplantation, probiotic and prebiotic supplementation, postbiotic or microbiota-derived metabolite supplementation, dietary interventions, and lifestyle strategies. Overall, the review highlights the critical role of the human microbiota in the pathogenesis and progression of COVID-19 and the potential of microbiota-targeted interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is among the most common cancers in the world with a low survival rate. Our previous study showed Short chain enoyl-CoA hydratase (ECHS1) could bind to HBsAg (HBs) and that ECHS1's localization in mitochondria induced HepG2 cell apoptosis. However, the role of the ECHS1 in energy metabolism and autophagy during hepatocellular carcinoma development remains undefined. We aimed to determine what ECHS1 does to energy metabolism and its effects on HCC progression. We performed CCK-8, EdU assays in hepatocellular carcinoma cell lines (HepG2 and HuH7) with stable ECHS1 knock-down. ATP and NADP+/NADPH levels were measured using an colorimetric assay. Our data demonstrated that ECHS1 silencing inhibited cell proliferation and induced autophagy. ECHS1 knockdown did not increase fatty acid synthesis, but decreased cellular ATP. This resulted in AMP-activated protein kinase (AMPK) activation and induced HCC cell autophagy. Our results showed that silencing ECHS1 to attenuate proliferation and induce autophagy may make it a novel cancer therapy target.

Gastric cancer (GC) is the second most frequent oncological cause of death, the fifth most common malignancy in the world, and accounts for 6.8% of all tumors. As an aggressive disease, GC is often diagnosed at an advanced stage, which is why it is a major cause of cancer-related death. In the last several decades, the incidence of GC has decreased, which should be credited to advances in diagnostic and therapeutic technologies including tumor-marker detection systems, imaging modalities, pathological methods, gastroscopy, and particularly surgical and pharmacologic interventions. Because they are economical, convenient, and noninvasive, the detection of conventional serum tumor biomarkers (e.g., CEA, CA19-9, and CA72-4) has been widely employed in the diagnosis and evaluation of GC. However, due to their poor specificity and sensitivity, these molecular markers cannot meet the demand of early GC detection. Hence, new and reliable tumor biomarkers are desperately needed. This review systematically summarizes the three most commonly used biomarkers of GC (e.g., CEA, CA19-9, and CA72-4) and addresses two categories of potential molecular biomarkers for the diagnosis of GC: microRNA and methylated DNA.

Objective: This study aimed to use visual mapping and bibliometric analysis to summarize valuable information on the tumor microenvironment (TME)-related research on hepatocellular carcinoma (HCC) in the past 20 years and to identify the research hotspots and trends in this field. Methods: We screened all of the relevant literature on the TME of HCC in the Web of Science database from 2003 to 2023 and analysed the research hotspots and trends in this field via VOSviewer and CiteSpace. Results: A total of 2,157 English studies were collected. According to the prediction, the number of papers that were published in the past three years will be approximately 1,394, accounting for 64.63%. China published the most papers (n=1,525) and had the highest total number of citations (n=32,253). Frontiers In Immunology published the most articles on the TME of HCC (n=75), whereas, Hepatology was the journal with the highest total number of citations (n=4,104) and average number of citations (n=91). The four clusters containing keywords such as “cancer-associated fibroblasts”, “hepatic stellate cells”, “immune cells”, “immunotherapy”, “combination therapy”, “landscape”, “immune infiltration”, and “heterogeneity” are currently hot research topics in this field. The keywords “cell death”, “ferroptosis”, “biomarkers”, and “prognostic features” have emerged relatively recently, and these research directions are becoming increasingly popular. Conclusions: We identified four key areas of focus in the study of the TME in HCC: the main components and roles in the TME, immunotherapy, combination therapy, and the microenvironmental landscape. Moreover, the result of our study indicate that effect of ferroptosis on the TME in HCC may become a future research trend. [ABSTRACT FROM AUTHOR]

Cirrhotic liver nodules can progress to hepatocellular carcinoma (HCC) through a multi-step carcinogenesis model, with dysplastic nodules being particularly high risk. Currently, monitoring the progression of non-HCC cirrhotic nodules is primarily through dynamic observation, but there is a lack of sensitive, efficient, and convenient methods. Dynamic monitoring and risk evaluation of malignant transformation are essential for timely treatment and improved patient survival rates. Routine liver biopsies are impractical for monitoring, and imaging techniques like ultrasound, computed tomography, and magnetic resonance imaging are not suitable for all patients or for accurately assessing subcentimeter nodules. Identifying serum biomarkers with high sensitivity, specificity, and stability, and developing a multi-index evaluation model, may provide a more convenient and efficient approach to monitoring pathological changes in cirrhotic nodules. [ABSTRACT FROM AUTHOR]

Motivation Recent advances in sequencing technology provide opportunities to study biological processes at a higher resolution. Cell type annotation is an important step in scRNA-seq analysis, which often relies on established marker genes. However, most of the previous methods divide the identification of cell types into two stages, clustering and assignment, whose performances are susceptible to the clustering algorithm, and the marker information cannot effectively guide the clustering process. Furthermore, their linear heuristic-based cell assignment process is often insufficient to capture potential dependencies between cells and types. Results Here, we present I nterpretable C ell T ype A nnotation based on s elf-training (sICTA), a marker-based cell type annotation method that combines the self-training strategy with pseudo-labeling and the nonlinear association capturing capability of Transformer. In addition, we incorporate biological priori knowledge of genes and pathways into the classifier through an attention mechanism to enhance the transparency of the model. A benchmark analysis on 11 publicly available single-cell datasets demonstrates the superiority of sICTA compared to state-of-the-art methods. The robustness of our method is further validated by evaluating the prediction accuracy of the model on different cell types for each single-cell data. Moreover, ablation studies show that self-training and the ability to capture potential dependencies between cells and cell types, both of which are mutually reinforcing, work together to improve model performance. Finally, we apply sICTA to the pancreatic dataset, exemplifying the interpretable attention matrix captured by sICTA. Availability and implementation The source code of sICTA is available in public at https://github.com/nbnbhwyy/sICTA. The processed datasets can be found at https://drive.google.com/drive/folders/1jbqSxacL%5fIDIZ4uPjq220C9Kv024m9eL. The final version of the model will be permanently available at https://doi.org/10.5281/zenodo.13474010 [ABSTRACT FROM AUTHOR]

Background: The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China. Methods: A cross-sectional study was conducted among 69,667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions. Results: The LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.8% (95%CI, 12.5-13%) and 6.4% (95%CI, 6-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ2 = 2931.9, P < 0.001). Conclusions: The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions. National screening strategy needs improvement. Regular training and quality assurance could improve the performance of TST and C-TST and close the detection gap of LTBI. [ABSTRACT FROM AUTHOR]

Although Akkermansia muciniphila (Am) plays a beneficial role as a probiotic in the treatment of metabolic syndrome, the mechanisms remain elusive. We tested the hypothesis that Am extracellular vesicles (AmEVs) protect against hypertension through modulation of gene expression in the kidneys of spontaneously hypertensive rats (SHRs). Extracellular vesicles purified from anaerobically cultured Am (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and SHRs weekly for 4 weeks. Renal cortical tissues isolated from both rat strains were analyzed by trichrome stain and RT-qPCR. AmEVs protect against the development of hypertension in SHRs without a serious adverse reaction. AmEVs increased the expression of vasocontracting Agt and At1ar as well as vasodilating At2r, Mas1 and Nos2 in the kidneys of both strains. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) is frequently associated with non-cardia type gastric cancer, and it is designated as a group I carcinogen. This study aimed to systematically review and meta-analyze the evidence on the prevalence of CagA status in people with gastric disorders in the Indo-Pacific region, and to examine the association of CagA positive in the risk of gastric disorders. This study focused on the Indo-Pacific region owing to the high disability adjusted life-years related to these disorders, the accessibility of efficient treatments for this common bacterial infection, and the varying standard of care for these disorders, particularly among the elderly population in the region. Methods: Relevant studies were identified in the health-related electronic databases including PubMed, Ovid, Medline, Ovid Embase, Index Medicus, and Google Scholar that were published in English between 1 January 2000, and 18 November 2023. For pooled prevalence, meta-analysis of proportional studies was done, after Freeman-Tukey double arcsine transformation of data. A random-effect model was used to compute the pooled odds ratio (OR) and 95% confidence interval (CI) to investigate the relationship between CagA positivity and gastric disorders. Results: Twenty-four studies from eight Indo-Pacific countries (Bhutan, India, Indonesia, Malaysia, Myanmar, Singapore, Thailand, Vietnam) were included. Overall pooled prevalence of CagA positivity in H. pylori-infected gastric disorders was 83% (95%CI = 73–91%). Following stratification, the pooled prevalence of CagA positivity was 78% (95%CI = 67–90%) in H. pylori-infected gastritis, 86% (95%CI = 73–96%) in peptic ulcer disease, and 83% (95%CI = 51–100%) in gastric cancer. Geographic locations encountered variations in CagA prevalence. There was a greater risk of developing gastric cancer in those with CagA positivity compared with gastritis (OR = 2.53,95%CI = 1.15–5.55). Conclusion: Findings suggest that the distribution of CagA in H. pylori-infected gastric disorders varies among different type of gastric disorders in the study countries, and CagA may play a role in the development of gastric cancer. It is important to provide a high standard of care for the management of gastric diseases, particularly in a region where the prevalence of these disorders is high. Better strategies for effective treatment for high-risk groups are required for health programs to revisit this often-neglected infectious disease. [ABSTRACT FROM AUTHOR]

Background: This study seeks to enhance the accuracy and efficiency of clinical diagnosis and therapeutic decision-making in hepatocellular carcinoma (HCC), as well as to optimize the assessment of immunotherapy response. Methods: A training set comprising 305 HCC cases was obtained from The Cancer Genome Atlas (TCGA) database. Initially, a screening process was undertaken to identify prognostically significant immune-related genes (IRGs), followed by the application of logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods for gene modeling. Subsequently, the final model was constructed using support vector machines-recursive feature elimination (SVM-RFE). Following model evaluation, quantitative polymerase chain reaction (qPCR) was employed to examine the gene expression profiles in tissue samples obtained from our cohort of 54 patients with HCC and an independent cohort of 231 patients, and the prognostic relevance of the model was substantiated. Thereafter, the association of the model with the immune responses was examined, and its predictive value regarding the efficacy of immunotherapy was corroborated through studies involving three cohorts undergoing immunotherapy. Finally, the study uncovered the potential mechanism by which the model contributed to prognosticating HCC outcomes and assessing immunotherapy effectiveness. Results: SVM-RFE modeling was applied to develop an OS prognostic model based on six IRGs (CMTM7, HDAC1, HRAS, PSMD1, RAET1E, and TXLNA). The performance of the model was assessed by AUC values on the ROC curves, resulting in values of 0.83, 0.73, and 0.75 for the predictions at 1, 3, and 5 years, respectively. A marked difference in OS outcomes was noted when comparing the high-risk group (HRG) with the low-risk group (LRG), as demonstrated in both the initial training set (P <0.0001) and the subsequent validation cohort (P <0.0001). Additionally, the SVMRS in the HRG demonstrated a notable positive correlation with key immune checkpoint genes (CTLA-4, PD-1, and PD-L1). The results obtained from the examination of three cohorts undergoing immunotherapy affirmed the potential capability of this model in predicting immunotherapy effectiveness. Conclusions: The HCC predictive model developed in this study, comprising six genes, demonstrates a robust capability to predict the OS of patients with HCC and immunotherapy effectiveness in tumor management. [ABSTRACT FROM AUTHOR]

Purpose: Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8+T cells (CD8+Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8+Ts on PVTT prognosis. Patients and Methods: This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan–Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed. Results: We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8+Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (< 100*10^9/L) and high CD8+Ts (> 320 cells/μL) had a better prognosis. Conclusion: We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8+Ts, and found that PT-8 formed by PLT and CD8+Ts was an excellent predictor of the prognosis of PVTT. [ABSTRACT FROM AUTHOR]

The gut microbiome regulates many important host physiological processes associated with cardiovascular health and disease; however, the impact of the gut microbiome on aldosterone is unclear. Investigating whether gut microbiota regulate aldosterone can offer novel insights into how the microbiome affects blood pressure. In this study, we aimed to determine whether gut microbiota regulate host aldosterone. We used enzyme-linked immunosorbent assays (ELISAs) to assess plasma aldosterone and plasma renin activity (PRA) in female and male mice in which gut microbiota are intact, suppressed, or absent. In addition, we examined urinary aldosterone. Our findings demonstrated that when the gut microbiota is suppressed following antibiotic treatment, there is an increase in plasma and urinary aldosterone in both female and male mice. In contrast, an increase in PRA is seen only in males. We also found that when gut microbiota are absent (germ-free mice), plasma aldosterone is significantly increased compared with conventional animals (in both females and males), but PRA is not. Understanding how gut microbiota influence aldosterone levels could provide valuable insights into the development and treatment of hypertension and/or primary aldosteronism. This knowledge may open new avenues for therapeutic interventions, such as probiotics or dietary modifications to help regulate blood pressure via microbiota-based changes to aldosterone. NEW & NOTEWORTHY: We explore the role of the gut microbiome in regulating aldosterone, a hormone closely linked to blood pressure and cardiovascular disease. Despite the recognized importance of the gut microbiome in host physiology, the relationship with circulating aldosterone remains largely unexplored. We demonstrate that suppression of gut microbiota leads to increased levels of plasma and urinary aldosterone. These findings underscore the potential of the gut microbiota to influence aldosterone regulation, suggesting new possibilities for treating hypertension. [ABSTRACT FROM AUTHOR]

Mesophotic coral ecosystems (MCEs; typically, 30–150 m depths) have traditionally been considered potential refuges for shallow-water organisms, but recent evidence suggests that this role is context-dependent. Here, we document a singular habitat at the upper mesophotic depth (- 30 m) in Xiaoliuqiu, Taiwan, and assess the changes in the benthic assemblage one year after a heatwave affected the reefs. In the habitat studied, abundant branching depth-specialist corals were found free-living and thriving on the sandy-rubble bottom amidst dense filamentous turf algae. In 2022, 63.6% of the corals were observed bleached, which was associated with severe heat stress affecting shallow reefs. The dominant coral at the time, Acropora tenella, suffered the most from the bleaching, with only 9.7% of its population remaining healthy. After one year, there was a noticeable shift in dominance from A. tenella to the previously cryptic Anacropora spp. without an obvious change in coral cover. We hypothesize that this rapid shift is driven by Anacropora spp., benefiting from the dense canopy provided by A. tenella. This suggests that the composition of understory organisms may play an important role in the resilience of some reefs affected by disturbance. The characteristics of this habitat, which consists mainly of deep-water specialists, and its susceptibility to stressors indicate that this habitat is unlikely to serve as a refuge for most shallow-water taxa. Our findings reinforce that the effectiveness of MCEs as refuges is not universal, and emphasize the importance of incorporating these unique habitats into conservation strategies and gaining a deeper understanding of their functions before they are lost. [ABSTRACT FROM AUTHOR]

To investigate the effect of bimaxillary surgery on the stress distribution of the temporomandibular joint (TMJ) in patients with mandibular retrognathia under unilateral molar clenching (UMC). Five patients with mandibular retrognathia (preoperative group) and ten asymptomatic subjects (control group) were recruited. In addition, patients treated with bimaxillary surgery were considered as the postoperative group. The muscle forces corresponding to UMC were applied. The results showed that the discal stresses in the postoperative group were significantly greater than those in the preoperative and control groups. Bimaxillary surgery plus UMC had a detrimental effect on the TMJ. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum. [ABSTRACT FROM AUTHOR]

Dendrobium nobile Lindl. alkaloids (DNLA) are considered important active ingredients of Dendrobium, which have a variety of pharmacological functions. Recent studies indicate that DNLA has beneficial activity in acute liver injury. However, the specific mechanism by which DNLA produces liver protective effects is stills unclear. This study was designed to determine whether regulation of autophagy is involved in the mode of action of DNLA in liver protection. Using CCl 4 -induced acute liver injury (ALI) and cell culture models, the molecular mechanism of DNLA-mediated autophagy regulation was studied. The results showed that DNLA significantly improved CCl 4 -induced liver damage and oxidative stress, which was confirmed in AML-12 cells. DNLA promoted autophagy in cells treated with CCl 4 , manifested by reduced protein expressions of p62 and LC3-II. Fluorescence imaging showed a decrease in the number of autophagosomes in AML-12 cells transfected with mCherry-GFP-LC3B. In addition, DNLA inhibited lysosomal membrane permeabilization by upregulating lysosomal associated membrane protein-1 (LAMP1), thereby promoting autophagy, preventing CCl 4 -induced mitochondrial dysfunction, and reducing the production of mitochondrial reactive oxygen species (ROS). While pretreatment of cells with lysosomal inhibitor chloroquine weakened mitochondrial protection elicited by DNLA, overexpression of mitochondrial-targeted SOD2 in AML-12 cells significantly blocked CCl 4 induced downregulation of LAMP1, thereby improving lysosome integrity and promoting lysosome dependent autophagy, suggesting that there may exist a bidirectional regulation between mitochondrial ROS and lysosome-autophagy activation. Collectively, these results demonstrated that DNLA can protect the liver injury mediated by dysregulation of lysosome-autophagy process through promoting ROS-lysosome-autophagy axis and improving mitochondrial damage., Competing Interests: Declarations Conflict of interest The authors declare that they have no competing interests. Institutional review board statement Animal handlings were fully compliance with the Chinese Experimental Animal Guideline and approved by the Animal Ethics Committee of Zunyi Medical University (ZMU21-2105–002) on 16 May 2021., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background and purpose: While HCC is an inflammation-associated cancer, CRLM develops on permissive healthy liver microenvironment. To evaluate the immune aspects of these two different environments, peripheral blood-(PB), peritumoral-(PT) and tumoral tissues-(TT) from HCC and CRLM patients were evaluated. Methods: 40 HCC and 34 CRLM were enrolled and freshly TT, PT and PB were collected at the surgery. PB-, PT- and TT-derived CD4+CD25+ Tregs, M/PMN-MDSC and PB-derived CD4+CD25− T-effector cells (Teffs) were isolated and characterized. Tregs' function was also evaluated in the presence of the CXCR4 inhibitor, peptide-R29, AMD3100 or anti-PD1. RNA was extracted from PB/PT/TT tissues and tested for FOXP3, CXCL12, CXCR4, CCL5, IL-15, CXCL5, Arg-1, N-cad, Vim, CXCL8, TGFβ and VEGF-A expression. Results: In HCC/CRLM-PB, higher number of functional Tregs, CD4+CD25hiFOXP3+ was detected, although PB-HCC Tregs exert a more suppressive function as compared to CRLM Tregs. In HCC/CRLM-TT, Tregs were highly represented with activated/ENTPD-1+Tregs prevalent in HCC. As compared to CRLM, HCC overexpressed CXCR4 and N-cadherin/vimentin in a contest rich in arginase and CCL5. Monocytic MDSCs were highly represented in HCC/CRLM, while high polymorphonuclear MDSCs were detected only in HCC. Interestingly, the function of CXCR4-PB-Tregs was impaired in HCC/CRLM by the CXCR4 inhibitor R29. Conclusion: In HCC and CRLM, peripheral blood, peritumoral and tumoral tissues Tregs are highly represented and functional. Nevertheless, HCC displays a more immunosuppressive TME due to Tregs, MDSCs, intrinsic tumor features (CXCR4, CCL5, arginase) and the contest in which it develops. As CXCR4 is overexpressed in HCC/CRLM tumor/TME cells, CXCR4 inhibitors may be considered for double hit therapy in liver cancer patients. [ABSTRACT FROM AUTHOR]

When braided dense-mesh stents are used to treat carotid stenosis, the structural mechanics of vascular stents, the contact mechanics with blood vessels, and the fluid mechanics in the blood environment need to be studied in depth to reduce the damage of stents to blood vessels and the incidence of in-stent restenosis. Three types of braided stents with 8, 16, and 24 strands and laser-cut stents with the corresponding size parameters were designed, and the bending behavior of each of these types of stent, deployment, and fluid dynamic analysis of the 24-strand braided stent were simulated. The results show that the bending stress of the 8-, 16-, and 24-strand braided stents is 46.33%, 50.24%, and 31.86% of that of their laser-cut counterparts. In addition, higher strand density of the braided stents was associated with greater bending stress; after the 24-strand braided stent was expanded within the stented carotid artery, the carotid stenosis rate was reduced from 81.52% to 46.33%. After stent implantation, the maximum stress on the vessel wall in a zero-pressure diastolic environment decreased from 0.34 to 0.20 MPa, the maximum pressure on the intravascular wall surface decreased from 4.89 to 3.98 kPa, the area of high-pressure region decreased, the wall shear force of the stenotic segment throat decreased, and blood flow increased in the stenosis segments. The braided stent had less bending stress and better flexibility than the laser-cut stent under the same stent size parameters; after the 24-strand braided stent was implanted into the stented vessel, it could effectively dilate the vessel, and the blood flow status was improved. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. Methods: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. Results: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. Conclusions: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment. [ABSTRACT FROM AUTHOR]

Introduction: Benign recurrent vertigo (BRV), Menière's disease (MD), and vestibular migraine (VM) show many similarities with regard to the course of vertigo attacks and clinical features. In this paper, we elaborate on the decreasing frequency of vertigo attacks observed in a previous study from our group by exploring changes in the duration and trigger factors of vertigo attacks in patients with BRV, MD, or VM. Methods: For this 3-year prospective cohort study in our tertiary referral center we recruited patients with a confirmed diagnosis of BRV, MD, or VM by a neurologist and otorhinolaryngologist in our center in 2015–2016. A study-specific questionnaire was used to assess the usual duration of vertigo attacks and their potential triggers every 6 months. Main outcome measures were changes in duration and trigger factors of vertigo attacks in the subgroups of patients with persisting attacks, which were analyzed using repeated measures logistic regression models. Results: 121 patients were included (BRV: n = 44; MD: n = 43; VM: n = 34) of whom 117 completed the 3-year follow-up period and 57 (48.7%) kept reporting vertigo attacks at one more follow-up measurements. None of the diagnosis groups showed statistically significant shortening of attack duration at the subsequent annual follow-up measurements compared to baseline. At baseline, stress and fatigue being reported as triggers for attacks differed significantly between the three groups (stress: BRV 40.9%, MD 62.8%, VM 76.5%, p = 0.005; fatigue: BRV 31.0%, MD 48.8%, VM 68.8%, p = 0.003). In the VM group, a consistent reduction of stress and fatigue as triggers was observed up until the 24- and the 30-month follow-up measurements, respectively, with odds ratios (ORs) ranging from 0.15 to 0.33 (all p < 0.05). In the MD group, a consistent reduction of head movements as trigger was observed from the 24-month measurement onward (ORs ranging from 0.07 to 0.11, all p < 0.05). Conclusion: Our study showed no reduction in vertigo attack duration over time in patients with BRV, MD, and VM who remain to have vertigo attacks. In VM and MD patients with persisting vertigo attacks stress, fatigue and head movements became less predominant triggers for vertigo attacks. [ABSTRACT FROM AUTHOR]

Radio frequency fingerprint (RFF) identification is a promising technique for identifying Internet of Things (IoT) devices. This paper presents a comprehensive survey on RFF identification, which covers various aspects ranging from related definitions to details of each stage in the identification process, namely signal preprocessing, RFF feature extraction, further processing, and RFF identification. Specifically, three main steps of preprocessing are summarized, including carrier frequency offset estimation, noise elimination, and channel cancellation. Besides, three kinds of RFFs are categorized, comprising I/Q signal-based, parameter-based, and transformation-based features. Meanwhile, feature fusion and feature dimension reduction are elaborated as two main further processing methods. Furthermore, a novel framework is established from the perspective of closed set and open set problems, and the related state-of-the-art methodologies are investigated, including approaches based on traditional machine learning, deep learning, and generative models. Additionally, we highlight the challenges faced by RFF identification and point out future research trends in this field. [ABSTRACT FROM AUTHOR]

Background: Analysis of hepatocellular carcinoma (HCC) single-cell sequencing data was conducted to explore the role of tumor-associated neutrophils in the tumor microenvironment. Methods: Analysis of single-cell sequencing data from 12 HCC tumor cores and five HCC paracancerous tissues identified cellular subpopulations and cellular marker genes. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to establish and validate prognostic models. xCELL, TIMER, QUANTISEQ, CIBERSORT, and CIBERSORT-abs analyses were performed to explore immune cell infiltration. Finally, the pattern of tumor-associated neutrophil roles in tumor microenvironmental components was explored. Results: A total of 271 marker genes for tumor-associated neutrophils were identified based on single-cell sequencing data. Prognostic models incorporating eight genes were established based on TCGA data. Immune cell infiltration differed between the high- and low-risk groups. The low-risk group benefited more from immunotherapy. Single-cell analysis indicated that tumor-associated neutrophils were able to influence macrophage, NK cell, and T-cell functions through the IL16, IFN-II, and SPP1 signaling pathways. Conclusion: Tumor-associated neutrophils regulate immune functions by influencing macrophages and NK cells. Models incorporating tumor-associated neutrophil-related genes can be used to predict patient prognosis and immunotherapy responses. [ABSTRACT FROM AUTHOR]

Background: Liver cancer accounts for more than 700,000 deaths each year making it the third leading cause of cancer-related deaths worldwide. Late diagnosis of the disease is the reason behind most deaths. Driver mutations are genetic alterations in tumor cells, which are responsible for the development of liver cancer; therefore, the identification of genetic biomarkers is necessary for the prediction and early diagnosis of liver cancer. Objectives: The main objective of this study is to identify pathogenic alleles that may act as potential biomarkers for the prediction of liver cancer. It also identifies the role of novel genes in liver cancer that are not known to cause the disease. Methods: The mutation data of non-coding variants were downloaded from the catalogue of somatic mutations in cancer (COSMIC) databases. Different bioinformatics tools were, then, used to retrieve mutations in liver cancer. The genetic alterations in hepato-cellular carcinoma (HCC) were analyzed. Results: The present study successfully identified pathogenic alleles (consistent mutations) along with a set of novel genes that might be involved in the development of liver cancer. It identified non-coding mutations near human genes and transcription factor binding sites of HepG2 cells. This study also identified mutations near the genes that are involved in the Ras/MAFK signaling pathway of the Hepatitis B virus. Conclusions: The pathogenic alleles identified in this study may provide targeted therapy for the treatment of liver cancer. The identification of novel genes may help to understand the progression of liver cancer at the molecular level. The identified driver mutations may act as potential biomarkers and therapeutic targets for early prediction and treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Aim: Gastric cancer (GC) is one of the most diagnosed cancers worldwide. GC is a heterogeneous disease whose pathogenesis has not been entirely understood. Besides, the GC prognosis for patients remains poor. Hence, finding reliable biomarkers and therapeutic targets for GC patients is urgently needed. Methods: GSE54129 and GSE26942 datasets were downloaded from Gene Expression Omnibus (GEO) database to detect differentially expressed genes (DEGs). Then, gene set enrichment analyses and protein-protein interactions were investigated. Afterward, ten hub genes were identified from the constructed network of DEGs. Then, the expression of hub genes in GC was validated. Performing survival analysis, the prognostic value of each hub gene in GC samples was investigated. Finally, the databases were used to predict microRNAs that could regulate the hub genes. Eventually, top miRNAs with more interactions with the list of hub genes were introduced. Results: In total, 203 overlapping DEGs were identified between both datasets. The main enriched KEGG pathway was "Protein digestion and absorption." The most significant identified GO terms included "primary alcohol metabolic process," "basal part of cell," and "extracellular matrix structural constituent conferring tensile strength." Identified hub modules were COL1A1, COL1A2, TIMP1, SPP1, COL5A2, THBS2, COL4A1, MUC6, CXCL8, and BGN. The overexpression of seven hub genes was associated with overall survival. Moreover, among the list of selected miRNAs, hsa-miR-27a-3, hsa-miR-941, hsa-miR-129-2-3p, and hsa-miR-1-3p, were introduced as top miRNAs targeting more than five hub genes. Conclusions: The present study identified ten genes associated with GC, which may help discover novel prognostic and diagnostic biomarkers as well as therapeutic targets for GC. Our results may advance the understanding of GC occurrence and progression. [ABSTRACT FROM AUTHOR]

Bacillus coagulans is a probiotic agent widely used in various industries. In this study, we isolated a novel strain of B. coagulans, X26, from soil and characterized its properties. X26 exhibited superior enzyme, acid, and biomass yields when compared with other bacterial probiotics and an antibiotic. Moreover, X26 significantly improved the body weight of rats, highlighting its potential for industrial development as a supplement for animals. To optimize the fermentation process of this bacterium, we adopted the response surface design. When X26 was cultured in a medium with 16.5 g/L maltose, 25.00 g/L yeast extract, and 3.5 g/L K2HPO4, the optimal yield was predicted to be 5.1 × 109 CFU/mL. Consistent with the prediction, the yield of X26 in a 500-mL flask culture was (5.12 ± 0.01) × 109 CFU/mL, and in a 30-L fermenter was (5.11 ± 0.02) × 109 CFU/mL, accounting for a 9.9-fold higher field than that with a basal medium before optimization. We further optimized the fermentation process in the 30-L and a 10-T fermenter, generating yields of (7.8 ± 0.2) × 109 CFU/mL (spore rate: 96.54%) and (8.7 ± 0.1) × 109 CFU/mL (spore rate: 97.93%), respectively. These yields and spore rates were achieved at 45–55°C, the typical fermentation temperature of B. coagulans. Our findings indicate that B. coagulans X26 is a promising probiotic with considerable potential for cost-effective industrial fermentation. [ABSTRACT FROM AUTHOR]

Introduction: Stroke is a major noninfectious disease that endangers patients' health. About 83% of patients have some degree of balance dysfunction. Rehabilitation training is an effective means to improve the balance function of stroke patients. The aim of this meta-analysis was to assess which of the eight rehabilitation training methods was more effective in promoting balance recovery. Material and methods: Eight studies of rehabilitation training to improve balance function in stroke patients were searched in PubMed, Scopus, Web of Science, Embase, Cochrane, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases. Data extraction was carried out by two independent researchers. The improvement in balance function included in the study was measured using the Berg Balance Scale (BBS). A random effects model was used to assess the mean difference in these values between patients who received different rehabilitation training and controls. Results: A total of 46 randomized controlled trials (RCTs) were included, including 3741 patients. Meta-analysis results showed that the clinical effectiveness in promoting balance recovery in stroke patients was ranked as follows: core stability training (odds ratio (OR) = 14.98, 95% confidence interval (CI): 8.18-27.44) > whole-body vibration training (OR = 10.27, 95% CI: 4.36-24.18) > mirror therapy (OR = 5.15, 95% CI: 2.40-11.04). Conclusions: This results suggested that core stability was more beneficial for improving balance function in stroke patients. [ABSTRACT FROM AUTHOR]

Mandibular deformities negatively affect the daily activities of the patients and may cause temporomandibular disorders (TMD). Bilateral sagittal split ramus osteotomy (BSSRO) and Le Fort I osteotomy are effective treatments to correct the mandibular deformities. The aim of this study was to investigate and compare the effects of the BSSRO with or without Le Fort I on the stress distributions of the temporomandibular joints (TMJs) of the patients with mandibular deformities under centric occlusion based on finite element (FE) method. Preoperative and postoperative cone-beam computed tomography (CBCT) images of twenty-four patients diagnosed with mandibular prognathism, including ten patients with BSSRO and another 14 patients with bimaxillary osteotomy (BSSRO with Le Fort I), were used to construct maxillofacial models. Ten asymptomatic individuals were also performed CBCT scanning and defined as the control group. In addition, the muscle forces and boundary conditions corresponding to centric occlusions were applied on each model. For the preoperative groups with both the BSSRO and bimaxillary osteotomies, the average peak contact stresses of the TMJs were both greater than those of the control group. After the surgeries, the contact stresses of the discs and temporal bones of both groups considerably decreased. However, the contact stresses on the condyles slightly increased after BSSRO but decreased after bimaxillary osteotomy. The TMJs of the patients with maxillofacial deformities suffered abnormal tensile and compressive stresses compared with the asymptomatic subjects under centric occlusion. Both of the BSSRO and bimaxillary osteotomy could improve the risk stress distributions of the TMJs. [ABSTRACT FROM AUTHOR]