USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart.

BACKGROUND: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy. METHODS: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice. Cardiac-specific knockout of USP28 in the db/db background mice was generated by crossbreeding db/m and Myh6-Cre+/USP28fl/fl mice. Recombinant adeno-associated virus serotype 9 carrying USP28 under cardiac troponin T promoter was injected into db/db mice. High glucose plus palmitic acid-incubated neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes were used to imitate diabetic cardiomyopathy in vitro. The molecular mechanism was explored through RNA sequencing, immunoprecipitation and mass spectrometry analysis, protein pull-down, chromatin immunoprecipitation sequencing, and chromatin immunoprecipitation assay. RESULTS: Microarray profiling of the UPS (ubiquitin-proteasome system) on the basis of db/db mouse hearts and diabetic patients' hearts demonstrated that the diabetic ventricle presented a significant reduction in USP28 expression. Diabetic Myh6-Cre+/USP28fl/fl mice exhibited more severe progressive cardiac dysfunction, lipid accumulation, and mitochondrial disarrangement, compared with their controls. On the other hand, USP28 overexpression improved systolic and diastolic dysfunction and ameliorated cardiac hypertrophy and fibrosis in the diabetic heart. Adeno-associated virus serotype 9-USP28 diabetic mice also exhibited less lipid storage, reduced reactive oxygen species formation, and mitochondrial impairment in heart tissues than adeno-associated virus serotype 9-null diabetic mice. As a result, USP28 overexpression attenuated cardiac remodeling and dysfunction, lipid accumulation, and mitochondrial impairment in high-fat diet/streptozotocin-induced type 2 diabetes mice. These results were also confirmed in neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes. RNA sequencing, immunoprecipitation and mass spectrometry analysis, chromatin immunoprecipitation assays, chromatin immunoprecipitation sequencing, and protein pull-down assay mechanistically revealed that USP28 directly interacted with PPARα (peroxisome proliferator-activated receptor α), deubiquitinating and stabilizing PPARα (Lys152) to promote Mfn2 (mitofusin 2) transcription, thereby impeding mitochondrial morphofunctional defects. However, such cardioprotective benefits of USP28 were largely abrogated in db/db mice with PPARα deletion and conditional loss-of-function of Mfn2. CONCLUSIONS: Our findings provide a USP28-modulated mitochondria homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts, suggesting that USP28 activation or adeno-associated virus therapy targeting USP28 represents a potential therapeutic strategy for diabetic cardiomyopathy.

Long-term Outcomes of Endovascular Repair for Blunt Thoracic Aortic Injury: A 10 Year Multi-center Experience.

OBJECTIVE: This study aimed to assess the long-term outcomes in patients treated by thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injuries (BTAI). MATERIALS AND METHODS: From January 2010 to December 2019, this retrospective observational study was conducted at 3 centers, involving 62 consecutive BTAI patients who underwent TEVAR. Computed tomography angiography scans were planned to be conducted at 6 months post-procedure, and annually thereafter. RESULTS: Technical success was achieved in all 62 procedures (100%), which included cases of dissection (n=35, 56.45%), pseudoaneurysm (n=20, 32.26%), and rupture (n=7, 11.29%). Mean injury severity score was 31.66±8.30. A total of 21 supra-arch branches were revascularized by chimney technique, with 12 cases involving the left subclavian artery (LSA) and 9 cases involving the left common carotid artery. In addition, 11 LSAs were covered during the procedure. The in-hospital mortality rate was 1.61% (n=1). The mean follow-up time was 86.82±30.58 months. The all-cause follow-up mortality rate was 3.28% (n=2). Stenosis or occlusion of 3 supra-arch branches (4.92%) was identified at follow-up, with 2 cases (3.28%) requiring re-intervention. No spinal cord ischemia, endoleak, or migration was observed. CONCLUSIONS: Despite only including patients with long-term follow-up, this study confirms the long-term safety and effectiveness of TEVAR for BTAI. For young BTAI patients, as the thoracic aorta increases with age, longer follow-up is needed to observe the potential mismatch between the endograft and the aorta. CLINICAL IMPACT: This study confirms the long-term safety and effectiveness of endovascular treatment for blunt thoracic aortic injury (BTAI). For young BTAI patients, as the thoracic aorta increases with age, longer follow-up is needed to observe the potential mismatch between the endograft and the aorta. Through a remarkably extended follow-up period (86.82±30.58 months) conducted at multiple centers in China, this study confirms the long-term safety and effectiveness of endovascular treatment for BTAI.

Comparative pharmacognosy and secondary metabolite analysis of Balanophorae herbs from different sources.

The Balanophorae are not only traditional Chinese herbal medicines but also functional foods with diverse sources. This study aimed to distinguish pharmacognostic characteristics and secondary metabolites among different species of Balanophorae. Eight species of Balanophorae herbs were harvested, including 21 batches with 209 samples. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze secondary metabolites of Balanophorae from 21 sources. Targeted metabolomic analysis was performed to compare differences among the groups. Rhopalocnemis phalloide and B. indica can be identified by their pharmacognostic characteristics. Then, 41 secondary metabolites were identified or characterized in the mixed extracts of the 209 samples, mainly phenolic acids, flavonoids, and their derivatives. The distribution of these secondary metabolites revealed apparent differences among different species. In addition, targeted metabolomic analysis suggested that the secondary metabolite profiles of seven species of Balanophorae showed noticeable differences, and differences were also observed among different growing regions. Finally, five important metabolic markers were screened to successfully distinguish B. laxiflora, B. harlandii, and B. polyandra, including three phenolic acids and two flavonoids. This is the first study to systematically compare both the morphology and secondary metabolites among different sources of Balanophorae, which could provide effective information for identifying diverse species.

Impact Analysis of COVID-19 Pandemic on Hospital Reviews on Dianping Website in Shanghai, China: Empirical Study.

BACKGROUND: In the era of the internet, individuals have increasingly accustomed themselves to gathering necessary information and expressing their opinions on public web-based platforms. The health care sector is no exception, as these comments, to a certain extent, influence people's health care decisions. During the onset of the COVID-19 pandemic, how the medical experience of Chinese patients and their evaluations of hospitals have changed remains to be studied. Therefore, we plan to collect patient medical visit data from the internet to reflect the current status of medical relationships under specific circumstances. OBJECTIVE: This study aims to explore the differences in patient comments across various stages (during, before, and after) of the COVID-19 pandemic, as well as among different types of hospitals (children's hospitals, maternity hospitals, and tumor hospitals). Additionally, by leveraging ChatGPT (OpenAI), the study categorizes the elements of negative hospital evaluations. An analysis is conducted on the acquired data, and potential solutions that could improve patient satisfaction are proposed. This study is intended to assist hospital managers in providing a better experience for patients who are seeking care amid an emergent public health crisis. METHODS: Selecting the top 50 comprehensive hospitals nationwide and the top specialized hospitals (children's hospitals, tumor hospitals, and maternity hospitals), we collected patient reviews from these hospitals on the Dianping website. Using ChatGPT, we classified the content of negative reviews. Additionally, we conducted statistical analysis using SPSS (IBM Corp) to examine the scoring and composition of negative evaluations. RESULTS: A total of 30,317 pieces of effective comment information were collected from January 1, 2018, to August 15, 2023, including 7696 pieces of negative comment information. Manual inspection results indicated that ChatGPT had an accuracy rate of 92.05%. The F1-score was 0.914. The analysis of this data revealed a significant correlation between the comments and ratings received by hospitals during the pandemic. Overall, there was a significant increase in average comment scores during the outbreak (P<.001). Furthermore, there were notable differences in the composition of negative comments among different types of hospitals (P<.001). Children's hospitals received sensitive feedback regarding waiting times and treatment effectiveness, while patients at maternity hospitals showed a greater concern for the attitude of health care providers. Patients at tumor hospitals expressed a desire for timely examinations and treatments, especially during the pandemic period. CONCLUSIONS: The COVID-19 pandemic had some association with patient comment scores. There were variations in the scores and content of comments among different types of specialized hospitals. Using ChatGPT to analyze patient comment content represents an innovative approach for statistically assessing factors contributing to patient dissatisfaction. The findings of this study could provide valuable insights for hospital administrators to foster more harmonious physician-patient relationships and enhance hospital performance during public health emergencies.

Elevated CHCHD4 orchestrates mitochondrial oxidative phosphorylation to disturb hypoxic pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a highly prevalent cardiopulmonary disorder characterized by vascular remodeling and increased resistance in pulmonary artery. Mitochondrial coiled-coil-helix-coiled-coil-helix domain (CHCHD)-containing proteins have various important pathophysiological roles. However, the functional roles of CHCHD proteins in hypoxic PAH is still ambiguous. Here, we aimed to investigate the role of CHCHD4 in hypoxic PAH and provide new insight into the mechanism driving the development of PAH. METHODS: Serotype 1 adeno-associated viral vector (AAV) carrying Chchd4 was intratracheally injected to overexpress CHCHD4 in Sprague Dawley (SD) rats. The Normoxia groups of animals were housed at 21% O2. Hypoxia groups were housed at 10% O2, for 8 h/day for 4 consecutive weeks. Hemodynamic and histological characteristics are investigated in PAH. Primary pulmonary artery smooth muscle cells of rats (PASMCs) are used to assess how CHCHD4 affects proliferation and migration. RESULTS: We found CHCHD4 was significantly downregulated among CHCHD proteins in hypoxic PASMCs and lung tissues from hypoxic PAH rats. AAV1-induced CHCHD4 elevation conspicuously alleviates vascular remodeling and pulmonary artery resistance, and orchestrates mitochondrial oxidative phosphorylation in PASMCs. Moreover, we found overexpression of CHCHD4 impeded proliferation and migration of PASMCs. Mechanistically, through lung tissues bulk RNA-sequencing (RNA-seq), we further identified CHCHD4 modulated mitochondrial dynamics by directly interacting with SAM50, a barrel protein on mitochondrial outer membrane surface. Furthermore, knockdown of SAM50 reversed the biological effects of CHCHD4 overexpression in isolated PASMCs. CONCLUSIONS: Collectively, our data demonstrated that CHCHD4 elevation orchestrates mitochondrial oxidative phosphorylation and antagonizes aberrant PASMC cell growth and migration, thereby disturbing hypoxic PAH, which could serve as a promising therapeutic target for PAH treatment.

Pristimerin protects against pathological cardiac hypertrophy through improvement of PPARα pathway.

Pristimerin (PM), serving as a biological component mainly obtained from Celastraceae and Hippocrateaceae families, has been extensively explored for its numerous pharmacological activities, especially anti-cancer activity. However, the function of PM on pathological cardiac hypertrophy is poorly understood. This work was intended to investigate the effects of PM on pressure-overload induced myocardial hypertrophy and its potential pathways. Mouse model of pathological cardiac hypertrophy was generated by transverse aortic constriction (TAC) or minipump administration of the ß-adrenergic agonist ISO for 4 weeks, and PM (0.5 mg/Kg/d, i.p.) was treated for 2 weeks. PPARα-/- mice received TAC surgery were used for mechanism exploration. Moreover, neonatal rat cardiomyocytes (NRCMs) were utilized to explore the effect of PM following Angiotensin II (Ang II, 1.0 µM) administration. We found that PM attenuated pressure-overload induced cardiac dysfunction, myocardial hypertrophy and fibrosis in mice. Likewise, PM incubation dramatically reversed Ang II-mediated cardiomyocytes hypertrophy in NRCMs. RNA-Sequence showed that PM selectively contributed to improvement of PPARα/PGC1 signaling, while silencing PPARα abrogated the beneficial effects of PM on Ang II-treated NRCMs. Importantly, PM ameliorated Ang II-induced mitochondrial dysfunction and decrease in metabolic genes, whereas knockdown of PPARα eliminated these alterations in NRCMs. Similarly, PM presented limited protective effects on pressure-overload induced systolic dysfunction and myocardial hypertrophy in PPARα deficient mice. Overall, this study revealed that PM exerted protective activity against pathological cardiac hypertrophy through improvement of PPARα/PGC1 pathway.

Angioplasty for Supra-Aortic Arterial Lesions from Takayasu Arteritis: Efficacy of Cutting Balloon Angioplasty Versus Conventional Balloon Angioplasty.

BACKGROUND: This retrospective study aimed to evaluate the safety and efficacy of cutting balloon angioplasty and conventional balloon angioplasty in supra-aortic arterial lesions caused by Takayasu arteritis. METHODS: A total of 46 patients with supra-aortic arterial lesions between January 2011 and December 2018 were included. Cutting balloon angioplasty was applied for 17 patients with 24 supra-aortic arterial lesions (group A), while 29 patients with 36 supra-aortic arterial lesions received conventional balloon angioplasty (group B). The preoperative clinical manifestation, operation result, and postoperative outcomes were recorded and compared in the 2 groups. RESULTS: Dizziness, visual disturbance, and unequal/absent pulses were the most common manifestations. The technical success of revascularization was 93.5% (43/46) in patients and 93.3% (56/60) in lesions. The stent implantation rate in group A was significantly lower than that in group B (4.2% vs. 50% in lesions, P < 0.05). Restenosis was the most common complication in both groups. Although the early (≤30 days) and late (>30 days) complications in group A were less than those in group B, there was no significant difference between the 2 groups (P > 0.05). Moreover, the primary-assisted patency of cutting balloon angioplasty and conventional balloon angioplasty at 1, 2, and 5 years were 66.7%, 62.5%, and 62.5% and 61.1%, 58.2%, and 49.8%, there was no significant difference between the 2 groups (P > 0.05), respectively. CONCLUSIONS: Compared with conventional balloon angioplasty, cutting balloon angioplasty could be considered a safe and effective alternative for supra-aortic arterial lesions caused by Takayasu arteritis, demonstrating better patency and clinical benefit.

HMGA2 contributes to vascular development and sprouting angiogenesis by promoting IGFBP2 production.

Angiogenesis is the process by which new blood vessels form from preexisting vessels and regulates the processes of embryonic development, wound healing and tumorigenesis. HMGA2 is involved in the occurrence of several cancers, but its biological role and the exact downstream genes involved in vascular development and sprouting angiogenesis remain largely unknown. Here, we first found that HMGA2 knockdown in zebrafish embryos resulted in defects of central artery formation. RNA sequencing revealed that IGFBP2 was significantly downregulated by interference with HMGA2, and IGFBP2 overexpression reversed the inhibition of brain vascular development caused by HMGA2 deficiency. In vitro, we further found that HMGA2 knockdown blocked the migration, tube formation and branching of HUVECs. Similarly, IGFBP2 protein overexpression attenuated the impairments induced by HMGA2 deficiency. Moreover, the promotion of angiogenesis by HMGA2 overexpression was verified in a Matrigel plug assay. We next found that HMGA2 bound directly to a region in the IGFBP2 promoter and positively regulated IGFBP2 expression. Interestingly, the mRNA expression levels of HMGA2 and IGFBP2 were increased significantly in the peripheral blood of hemangioma patients, indicating that overexpression of HMGA2 and IGFBP2 results in vessel formation, consistent with the results of the in vivo and in vitro experiments. In summary, our findings demonstrate that HMGA2 promotes central artery formation by modulating angiogenesis via IGFBP2 induction.

False Lumen Stent-Grafts for Repair of Postdissection Aortic Aneurysms.

PURPOSE: To evaluate the safety and efficacy of false lumen (FL) stent-grafts in the treatment of postdissection aortic aneurysms. MATERIALS AND METHODS: Eleven patients who underwent endovascular repair using FL stent-grafts from January 2016 to June 2019 were included. Among them, 2 patients had a prior history of type A aortic dissection, whereas 9 had undergone a prior endovascular repair for type B aortic dissection. Computed tomography angiography was performed to evaluate the reintervention and technical success rate, aortic remodeling, and other related aortic complications. RESULTS: The mean age of patients was 55.6 ± 10.4 years. Technical success was achieved in all patients, and neither early mortality nor paralysis occurred. In total, 8 visceral branch arteries originating from the FL were reconstructed. The true lumen areas at the celiac axis, superior mesenteric artery, renal artery, and abdominal aortic bifurcation were significantly increased from 230.1 mm2 to 312.3 mm2, 212.1 mm2 to 277.5 mm2, 209.1 mm2 to 291.6 mm2, and 214.4 mm2 to 300.6 mm2, respectively (P < .05). The total diameter of the aorta at the 4 designated levels was stable or had shrunk in all patients. At a mean follow-up of 18.9 ± 7.6 months, 1 patient received re-intervention owing to iliac stent-graft occlusion. No aortic-related mortality occurred. CONCLUSIONS: FL stent-grafts can safely and effectively treat patients with postdissection aortic aneurysms. This strategy can be used to promote thrombosis of the FL and aortic remodeling. A larger sample and an extended follow-up period are needed to produce more conclusive results.

Physician-Modified Branched Double-Trunk Stent-Graft (PBDS) for Thoracoabdominal Aortic Aneurysm.

PURPOSE: To describe the preliminary experience of using physician-modified, branched, double-trunk stent-grafts (PBDS) for treating thoracoabdominal aortic aneurysms (TAAA). MATERIALS AND METHODS: Ten (10) patients with TAAA were included in the study from June 2017 to March 2020. The technical success, perioperative complications, re-intervention, and patency of branch arteries were assessed. RESULTS: The technical success rate was 100%. There were four type III endoleaks (40%) recorded in the perioperative period. The median follow-up was 13.4 months (range, 3-36 months). During follow-up, two renal stent-graft occlusions (2 of 37 visceral arteries reconstructed, 5.4%), one cerebral infarction (1 of 10, 10%) and one paraplegia (1 of 10, 10%) occurred. No aortic-related death was recorded. CONCLUSION: PBDS is useful in sealing TAAA and preventing visceral branches, providing an option for patients unsuited for open surgical repair. A larger sample size of patients is required to confirm the safety and effectiveness of this technique.

Endovascular repair combined with staged drainage for the treatment of infectious aortic aneurysm: a case report.

BACKGROUND: Infectious aortic aneurysm, defined as a focal dilation of an infectious arterial wall, is an uncommon life-threatening disease. Compared with open surgery, endovascular repair yields acceptable clinical outcomes. However, residual tissue infection may increase the risk of secondary intervention. Here, we present a successful case of endovascular repair combined with staged drainage for the treatment of infectious aortic aneurysm. CASE PRESENTATION: A 58-year-old man presented to hospital with a 3-day history of lower back pain radiating to the back associated with fever. The dynamic imaging characteristics revealed rapid progress of infectious abdominal aortic aneurysm with negative blood culture. The patient underwent endovascular repair and salmonella enteritidis was identified through drain culture. CONCLUSIONS: Endovascular procedure and staged drainage can be feasible and effective option in selected cases.

Endovascular Treatment of Distal False Lumen Aneurysmal Expansion in Chronic Type B Aortic Dissection with True Lumen Occlusion.

Aneurysmal degeneration of distal false lumen after primary endovascular exclusion or open replacement of the proximal entry tear was not rare. Currently, no endovascular reintervention techniques have been established for this condition because of its pathological complexity, especially when the true lumen is severely stenosed or even occluded. In this report, we presented a case of chronic type B aortic dissection, whose false lumen of the abdominal aorta significantly expanded and true lumen occluded after the primary endovascular treatment of the proximal entry tear. Therefore, this-time endovascular treatment reconstructed the renal artery and lower limb artery through the false lumen. The 3-year follow-up computed tomography angiography confirmed that the reconstructed renal artery was patent and no endoleak was detected. Complete thrombosis and shrink of the aneurysmal false lumen were confirmed. Thus, endovascular treatment could be a feasible strategy for this subset of patients.

Endovascular Reconstruction from Aortic Valve to Aortic Arch Using One-Piece Valved-Fenestrated Stent Graft with a Branch: A Proof-of-Concept Study.

OBJECTIVE: To explore the feasibility of endovascular reconstruction of aortic root including aortic valve, sinus of valsalva and ascending aorta by a single stent-graft, a novel valved stent-graft with two fenestrae for preserving the coronary arteries was designed and performed in-vitro on a pig heart based circulation simulating system. METHODS: Pig hearts were harvested from 30 healthy adult female pigs weighing between 60-65 kilograms. Before sacrifice, all the pigs received aortic computed tomography angiography (CTA) examinations and morphologic parameters of aortic root were measured. Then we customized the valved stent-grafts according to the CTA measurements. After the pig heart was fixed on the special platform according to the original orientation and connected to the circulation system, the stent graft was delivered through transapical access and covered the segment from aortic annulus to proximal part of aortic arch under DSA (digital subtraction angiography) guidance. Then changes of coronary flow before and after the procedure and fenestration alignment with coronary ostia were analyzed. RESULTS: The overall technical success rate was 100%. The valve functions tested by ultrasound were in good condition under 120 mmHg circulation pressure. The flow of left coronary artery (LCA) did not decrease, but increased after the stent-graft implantation (340 ± 2.06 mL/min versus 288 ± 5.29 mL/min, P < .05). Similarly, the flow of right coronary artery (RCA) also increased (392 ± 9.17 mL/min versus 348 ± 8.01 mL/min; P < .05). The final angiography confirmed that both coronary arteries were patent. When generally observed from outer wall of valsalva sinus, both RCA and LCA orifices were aligned with the fenestrae. In 4 cases, the autologous valve leaflets blocked nearly 20% of the LCA fenestra's area, but the flow did not significantly decrease in these cases. CONCLUSION: Stimulated on a pig heart-based circulation simulation system, the one-piece valved-fenestrated stent graft with a branch could be delivered via the transapical access and deployed accurately, which achieved endovascular reconstruction of aortic valve, sinus of valsalva and ascending aorta while preserving the coronary artery perfusion by fenestrations. More in-vivo experiments on animal models are mandatory to further verify its efficacy and safety.

Multifunctional thiolated chitosan/puerarin composite hydrogels with pH/glutathione dual responsiveness for potential drug carriers.

Puerarin (PUE), a natural and biologically active isoflavone extracted from Chinese medicine Pueraria lobata, can self-assemble to form a hydrogel without other chemical modifications. However, although PUE hydrogel has pH responsivity, but it is difficult to adapt to the changeable pathological environment. Therefore, thiolated chitosan (TCS) is synthesized and hybridized with PUE hydrogel to prepare TCS10/PUE composite hydrogel. The results of rheological measurement showed that the resultant composite hydrogels inherited the low loss performance of TCS hydrogel, which means that they have stronger elasticity. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images displayed that TCS10/PUE composite hydrogel has a fibrous-network structure. X-Ray Diffractometer (XRD) and Fourier transform infrared spectroscopy (FT-IR) proved the existence of hydrogen bonds and disulfide bonds in the formation of composite hydrogel. Degradation experiment showed that TCS10/PUE composite hydrogels have pH and glutathione (pH/GSH) dual sensitivity. Furthermore, TCS10/PUE composite hydrogels exhibited multi-functionality including thixotropy, cytocompatibility, antibacterial and anti-inflammatory properties. Berberine chloride hydrate (BCH) was further used as a model drug for in vitro release study. BCH and PUE could be released cooperatively under pH/GSH dual responsivity. These results indicated that the resultant composite hydrogel has eminent pH/GSH dual responsivity and could act as a potential new intelligent drug carrier.

The chemical composition of Diwu YangGan capsule and its potential inhibitory roles on hepatocellular carcinoma by microarray-based transcriptomics.

The Traditional Chinese Medicine compound preparation known as Diwu Yanggan capsule (DWYG) can effectively hinder the onset and progression of hepatocellular carcinoma (HCC), which is recognized worldwide as a significant contributor to fatalities associated with cancer. Nevertheless, the precise mechanisms implicated have remained ambiguous. In present study, the model of HCC was set up by the 2-acetylaminofluorene (2-AAF)/partial hepatectomy (PH) in rats. To confirm the differentially expressed genes (DEGs) identified in the microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted. In the meantime, the liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF-MS/MS) was employed to characterize the component profile of DWYG. Consequently, the DWYG treatment exhibited the ability to reverse 51 variation genes induced by 2-AAF/PH. Additionally, there was an overlap of 54 variation genes between the normal and model groups. Upon conducting RT-qPCR analysis, it was observed that the expression levels of all genes were increased by 2-AAF/PH and subsequently reversed after DWYG treatment. Notably, the fold change of expression levels for all genes was below 0.5, with 3 genes falling below 0.25. Moreover, an investigation was conducted to determine the signaling pathway that was activated/inhibited in the HCC group and subsequently reversed in the DWYG group. Moreover, the component profile of DWYG encompassed a comprehensive compilation of 206 compounds that were identified or characterized. The findings of this study elucidated the potential alleviative mechanisms of DWYG in the context of HCC, thereby holding significant implications for its future clinical utilization and widespread adoption.

Targeted Screening of Curcumin Derivatives as Pancreatic Lipase Inhibitors Using Computer-Aided Drug Design.

Curcumin has demonstrated promising preclinical antiobesity effects, but its low bioavailability makes it difficult to exert its full effect at a suitable dose. The objective of this study was to screen curcumin derivatives with enhanced bioavailability and lipid-lowering activity under the guidance of computer-aided drug design (CADD). CAAD was used to perform virtual assays on curcumin derivatives to assess their pharmacokinetic properties and effects on pancreatic lipase activity. Subsequently, 19 curcumin derivatives containing 5 skeletons were synthesized to confirm the above virtual assay. The in vitro pancreatic lipase inhibition assay was employed to determine the half-maximal inhibitory concentration (IC50) of these 19 curcumin derivatives. Based on CADD analysis and in vitro pancreatic lipase inhibition, 2 curcumin derivatives outperformed curcumin in both aspects. Microscale thermophoresis (MST) experiments were employed to assess the binding equilibrium constants (K d) of the aforementioned 2 curcumin derivatives, curcumin, and the positive control drug with pancreatic lipase. Through virtual screening utilizing a chemoinformatics database and molecular docking, 6 derivatives of curcumin demonstrated superior solubility, absorption, and pancreatic lipase inhibitory activity compared to curcumin. The IC50 value for 1,7-bis(4-hydroxyphenyl)heptane-3,5-dione (C4), which displayed the most effective inhibitory effect, was 42.83 µM, while the IC50 value for 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (C6) was 98.62 µM. On the other hand, the IC50 value for curcumin was 142.24 µM. The MST experiment results indicated that the K d values of C4, C6, and curcumin were 2.91, 18.20, and 23.53 µM, respectively. The results of the activity assays exhibited a relatively high degree of concordance with the outcomes yielded by CADD screening. Under the guidance of CADD, the targeted screening of curcumin derivatives with excellent properties in this study exhibited high-efficiency and low-cost benefits.

Minimally Invasive Endovascular Repair for Nondissected Ascending Aortic Disease: A Systematic Review.

Objective: The aim of this study is to evaluate the efficacy of endovascular treatment for nondissected diseases of the ascending aorta. Data Sources. PubMed, Embase, and SciELO. Review Methods. In this study, we conducted a search on the PubMed, Embase, and SciELO databases for all cases of ascending aortic endovascular repair included in the literature published between January 2007 and July 2023, excluding type A aortic dissection. We reviewed 56 case reports and 7 observational studies included in this study, assessing the techniques, equipment, procedural steps, and results. We summarized the age, complications, follow-up time, and access route. Results: This study includes 63 articles reporting 105 patients (mean age: 64.96 ± 17.08 years) who received endovascular repair for nondissected ascending aortic disease. The types of disease include aneurysm (N = 16), pseudoaneurysm (N = 71), penetrating aortic ulcer (N = 10), intramural hematoma (N = 2), thrombosis (N = 2), iatrogenic coarctation (N = 1), and rupture of the aorta (N = 3). The success rate of surgery is 99.05% (104/105). Complications include endoleak (10.48%, 11/105), stroke (5.71%, 6/105), postoperative infection (1.91%, 2/105), acute renal failure (0.95%, 1/105), aortic rupture (0.95%, 1/105), thrombosis (0.95%, 1/105), and splenic infarction (0.95%, 1/105). Five patients required conversion to open surgery, two patients underwent endovascular reintervention, and four of these five patients underwent surgery due to endoleak. Early mortality was 2.86% (3/105). Conclusion: While the viability and results of endovascular repair for the treatment of ascending aortic disease are acknowledged in some circumstances, further research is needed to determine the safety and effectiveness of endovascular treatment for ascending aortic disease.

TEVAR for aortic arch lesions combining physician-modified endograft and in-situ fenestration.

BACKGROUND: The aim of this retrospective study was to investigate the outcomes of combining physician-modified endograft (PMEG) and in-situ fenestration (ISF) for aortic arch repair. METHODS: A retrospective analysis was performed in 12 patients with aortic arch pathologies who underwent thoracic endovascular aortic repair with PMEG and ISF between June 2019 and February 2020. RESULTS: Revascularizations of supra-aortic arteries were successfully performed in 91.7% patients (11/12). One patient with aberrant right subclavian artery was unsuccessful because of tortuosity and sharp angle. One patient received endovascular exclusion by Viabahn due to artery injury of the femoral access. During the follow-up (mean 22.7 months), one patient underwent Bentall surgery because of retrograde type A aortic dissection, and one patient received coils embolization due to occurrence of a type I endoleak. In addition, one patient died of myocardial infarction 13 months after surgery. Results obtained after computed tomography angiography confirmed patency of all the supra-aortic arteries. CONCLUSIONS: Combining PMEG and ISF could be a feasible option for aortic arch lesions in selected patients. Long-term durability concerns require further evaluation.

Dynamical changes of tea metabolites fermented by Aspergillus cristatus, Aspergillus neoniger and mixed fungi: A temporal clustering strategy for untargeted metabolomics.

Dark tea fermentation involves various fungi, but studies focusing on the mixed fermentation in tea remain limited. This study investigated the influences of single and mixed fermentation on the dynamical alterations of tea metabolites. The differential metabolites between unfermented and fermented teas were determined using untargeted metabolomics. Dynamical changes in metabolites were explored by temporal clustering analysis. Results indicated that Aspergillus cristatus (AC) at 15 days, Aspergillus neoniger (AN) at 15 days, and mixed fungi (MF) at 15 days had respectively 68, 128 and 135 differential metabolites, compared with unfermentation (UF) at 15 days. Most of metabolites in the AN or MF group showed a down-regulated trend in cluster 1 and 2, whereas most of metabolites in the AC group showed an up-regulated trend in cluster 3 to 6. The three key metabolic pathways mainly composed of flavonoids and lipids included flavone and flavonol biosynthesis, glycerophospholipid metabolism and flavonoid biosynthesis. Based on the dynamical changes and metabolic pathways of the differential metabolites, AN showed a predominant status in MF compared with AC. Together, this study will advance the understanding of dynamic changes in tea fermentation and provide valuable insights into the processing and quality control of dark tea.