Clinical characteristics and treatment compounds of obesity-related kidney injury.

Disorders in energy homeostasis can lead to various metabolic diseases, particularly obesity. The obesity epidemic has led to an increased incidence of obesity-related nephropathy (ORN), a distinct entity characterized by proteinuria, glomerulomegaly, progressive glomerulosclerosis, and renal function decline. Obesity and its associated renal damage are common in clinical practice, and their incidence is increasing and attracting great attention. There is a great need to identify safe and effective therapeutic modalities, and therapeutics using chemical compounds and natural products are receiving increasing attention. However, the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN. In this review, we summarize the important clinical features and compound treatment strategies for obesity and obesity-induced kidney injury. We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation, oxidative stress, insulin resistance, fibrosis, kidney lipid accumulation, and dysregulated autophagy. In addition, detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized. The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases, fostering the anticipation of novel insights in this domain.

Laparoscopic dissection of the first and second porta hepatis along Laennec's capsule via "Hepatic Serosal Incision" approach: How I do it.

To provide a standardized approach for laparoscopic access to dissection of the first and second porta hepatis. By opening a portion of the hepatic serosa and subsequently exposing the hepatic Laennec's capsule, dissection of the first and second porta hepatis was performed along the Laennec's capsule. Utilizing the "Hepatic Serosal Incision" approach along the Laennec's capsule enabled the precise dissection of the left and right hepatic pedicles of the first porta hepatis and the root of the hepatic veins at the second porta hepatis under laparoscopy. This method allows for rapid and accurate access to the space between Laennec's capsule and the hepatic hilar plate system under laparoscopy as well as clear exposure of the root of the hepatic veins and their branches, facilitating more precise laparoscopic anatomical liver resection.

Cystic Plate Approach Combined with Indocyanine Green（ICG） Fluorescence in Laparoscopic Anatomical Hepatectomy.

BACKGROUND: The in-depth understanding of the fine anatomy of the liver has promoted the development of modern liver surgery. With the rapid popularity of laparoscopic hepatectomy, the membrane structure of the liver and its ability to dissect the intra- and extra-hepatic vascular system more conveniently and accurately has been gradually emphasized. OBJECTIVE: Exploring the value of extrahepatic sheath dissection of the hepatic pedicle in minimally invasive anatomical hepatectomy with cystic plate approach. This study aims to assess the benefits of integrating the cystic plate approach with real-time guided laparoscopic anatomical hepatectomy, in comparison with conventional laparoscopic anatomical hepatectomy. MATERIALS AND METHODS: Based on the theory of cystic plate and hepatic portal plate, we have pioneered the fluorescence real-time guided cystic plate approach in hepatectomy. The article focuses on the anatomical knowledge and technical difficulties of anatomical hepatectomy with fluoroscopic laparoscopic cystic plate approach and explores the safety and practicality of the cystic plate approach in laparoscopic anatomical hepatectomy. Additionally, a retrospective cohort study was also conducted to compare the operation time, intraoperative blood loss, and postoperative complications between the cystic plate approach and the conventional approach during fluoroscopic laparoscopic hepatectomy. RESULTS: A total of 38 patients who met the inclusion criteria underwent laparoscopic hepatectomy between January 2019 and November 2022. No significant disadvantages were found in terms of operation time and intraoperative blood loss during the surgeries. Furthermore, the postoperative indications, including liver function indexes on the first postoperative day, WBC, and the postoperative hospital stay, were also not affected, thus proving the safety of the cystic approach. Importantly, through the cystic plate approach, the target liver pedicle was fully freed, and then the segments to be resected were precisely marked by positive or negative staining, followed by hepatectomy under real-time fluoroscopic guidance. This approach is extremely advantageous in anatomical liver segment resections, especially in right posterior lobe or hemi-hepatectomy, without increasing intraoperative bleeding or postoperative complication rates. CONCLUSION: This technique allows for easy and safe freeing of the target liver pedicle using membrane structures, and also allows for precise anatomical hepatectomy in combination with real-time fluoroscopic laparoscopic navigation.

CLSTN3B enhances adipocyte lipid droplet structure and function via endoplasmic reticulum contact.

Interorganelle contacts facilitate material exchanges and sustain the structural and functional integrity of organelles. Lipid droplets (LDs) of adipocytes are responsible for energy storage and mobilization responding to body needs. LD biogenesis defects compromise the lipid-storing capacity of adipocytes, resulting in ectopic lipid deposition and metabolic disorders, yet how the uniquely large LDs in adipocytes attain structural and functional maturation is incompletely understood. Here we show that the mammalian adipocyte-specific protein CLSTN3B is crucial for adipocyte LD maturation. CLSTN3B employs an arginine-rich segment to promote extensive contact and hemifusion-like structure formation between the endoplasmic reticulum (ER) and LD, allowing ER-to-LD phospholipid diffusion during LD expansion. CLSTN3B ablation results in reduced LD surface phospholipid density, increased turnover of LD-surface proteins, and impaired LD functions. Our results establish the central role of CLSTN3B in the adipocyte-specific LD maturation pathway that enhances lipid storage and maintenance of metabolic health under caloric overload.

"Hooking method" for hepatic inflow control: a new approach for laparoscopic Pringle maneuver.

BACKGROUND: The laparoscopic Pringle maneuver is crucial for controlling bleeding during laparoscopic hepatectomy. In this study, we introduce a new laparoscopic Pringle maneuver and preliminarily investigate its application in laparoscopic hepatectomy. METHODS: We collected and analyzed the clinical data of 17 consecutive patients who underwent laparoscopic hepatectomy at the Department of Hepatic Surgery, the First Affiliated Hospital of the University of Science and Technology of China, from January 2022 to January 2023. All patients underwent the hooking method for intermittent occlusion of hepatic inflow. Intraoperative and postoperative clinical indices were observed and recorded. RESULTS: All 17 patients underwent laparoscopic hepatectomy with hepatic inflow control using the hooking method. Four patients with adhesions under the hepatoduodenal ligament successfully had occlusion loops placed using the hooking method combined with Zhang's modified method during surgery. The median occlusion time for the 17 patients was 34 (12-60) min, and the mean operation time was 210 ± 70 min. The mean intraoperative blood loss was 145 ± 86 ml, and no patients required intraoperative blood transfusion. The patients' postoperative peak AST was 336 ± 183 U/L, and the postoperative peak ALT was 289 ± 159 U/L. Postoperative complications occurred in 2 patients (11.8%), including 1 Clavien-Dindo grade I and 1 Clavien-Dindo grade II complication. No Clavien-Dindo grade IIIa or higher complications or deaths occurred in any patient. None of the patients developed portal vein thrombosis or hepatic artery aneurysm formation. The median postoperative hospital stay was 6 (4-14) days. CONCLUSION: The hooking method combines the advantages of both intracorporeal Pringle maneuver and extracorporeal Pringle maneuver. It is a simple, safe, and effective method for controlling hepatic inflow and represents a promising approach for performing totally intracorporeal laparoscopic Pringle maneuver.

How to perform laparoscopic right hepatic pedicle dissection: cystic plate approach based on the 'red/yellow demarcation line'.

How to perform laparoscopic right hepatic pedicle dissection: cystic plate approach based on the 'red/yellow demarcation line'.

Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice.

BACKGROUND: Myricetin (3,5,7-trihydroxy-2-(3,4,5-tri hydroxyphenyl)-4-benzopyrone) is a common flavonol extracted from many natural plants and Chinese herb medicines and has been demonstrated to have multiple pharmacological activities, such as anti-microbial, anti-thrombotic, neuroprotective, and anti-inflammatory effects. Previously, myricetin was reported to target Mpro and 3CL-Pro-enzymatic activity to SARS-CoV-2. However, the protective value of myricetin on SARS-Cov-2 infection through viral-entry facilitators has not yet been comprehensively understood. PURPOSE: The aim of the current study was to evaluate the pharmacological efficacy and the mechanisms of action of myricetin against SARS-CoV-2 infection both in vitro and in vivo. METHODS: The inhibitory effects of myricetin on SARS-CoV-2 infection and replication were assessed on Vero E6 cells. Molecular docking analysis and bilayer interferometry (BLI) assays, immunocytochemistry (ICC), and pseudoviruses assays were performed to evaluate the roles of myricetin in the intermolecular interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and angiotensin-converting enzyme 2 (ACE2). The anti-inflammatory potency and mechanisms of myricetin were examined in THP1 macrophages in vitro, as well as in carrageenan-induced paw edema, delayed-type hypersensitivity (DTH) induced auricle edema, and LPS-induced acute lung injury (ALI) animal models. RESULTS: The results showed that myricetin was able to inhibit binding between the RBD of the SARS-CoV-2 S protein and ACE2 through molecular docking analysis and BLI assay, demonstrating its potential as a viral-entry facilitator blocker. Myricetin could also significantly inhibit SASR-CoV-2 infection and replication in Vero E6 cells (EC50 55.18 µM), which was further validated with pseudoviruses containing the RBD (wild-type, N501Y, N439K, Y453F) and an S1 glycoprotein mutant (S-D614G). Moreover, myricetin exhibited a marked suppressive action on the receptor-interacting serine/threonine protein kinase 1 (RIPK1)-driven inflammation and NF-kappa B signaling in THP1 macrophages. In animal model studies, myricetin notably ameliorated carrageenan-induced paw edema in rats, DTH induced auricle edema in mice, and LPS-induced ALI in mice. CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.

Deciphering the molecular mechanisms of Maxing Huoqiao Decoction in treating pulmonary fibrosis via transcriptional profiling and circRNA-miRNA-mRNA network analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung condition with unknown etiology and high mortality. Chinese herbal medicine has been used for more than a thousand years to treat various lung diseases. PURPOSE: The current study aimed to examine whether Chinese herbal Maxing Huoqiao Decoction (MXHQD) exerts therapeutic effects on IPF and to further uncover its underlying molecular mechanisms. METHODS: Mouse model of acute lung injury (ALI) or IPF was induced by intratracheal instillation of LPS or bleomycin, respectively. ALI mice were treated with MXHQD for 7 days, and lung tissues were taken for test after modeling 24 h. IPF mice were gavaged for 21 days after modeling. Lung tissues were subjected to whole transcriptome detection, and the differential RNAs were experimentally verified. RESULTS: The results showed that MXHQD alleviated the computed tomography (CT) and the pathological degree changes in mice with IPF, improved changes in the expression of fibrosis related genes and reduced the hydroxyproline expression in IPF mice. MXHQD also decreased the cell numbers in bronchoalveolar lavage fluids, and the expression levels of the inflammatory factors in the ALI mice lung tissues were significantly inhibited. By applying whole transcriptome analysis, results showed that MXHQD acted on 40 mRNAs, 15 miRNAs, 25 novel lncRNAs and 17 circRNAs to resist pulmonary fibrosis. The competing endogenous RNA (ceRNA) network diagram showed that the multiple components of MXHQD against fibrosis through a network of multiple targets. The differential mRNAs were mainly related to the innate immune response and the defense response to virus. Then the expression of mRNAs in the differential mRNA-miRNA-differential circRNA network in the lung tissue of IPF was verified. The expression of ZBP1 and ISG15 related to immune system and anti virus was verified at both gene and protein expressions. MXHQD could significantly inhibit the elevation of ZBP1 and ISG15 factors induced by the fibrosis model. CONCLUSION: Overall, our findings provide compelling evidence that MXHQD can alleviate IPF by modulating innate immunity. This is the first study to reveal the molecular mechanism underlying the multi-components, multi-channels and multi-targets anti-IPF immune injury of MXHQD, and supports its potential clinical application for IPF.

Hypothalamic Grb10 enhances leptin signalling and promotes weight loss.

Leptin acts on hypothalamic neurons expressing agouti-related protein (AgRP) or pro-opiomelanocortin (POMC) to suppress appetite and increase energy expenditure, but the intracellular mechanisms that modulate central leptin signalling are not fully understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an adaptor protein that binds to the insulin receptor and negatively regulates its signalling pathway, can interact with the leptin receptor and enhance leptin signalling. Ablation of Grb10 in AgRP neurons promotes weight gain, while overexpression of Grb10 in AgRP neurons reduces body weight in male and female mice. In parallel, deletion or overexpression of Grb10 in POMC neurons exacerbates or attenuates diet-induced obesity, respectively. Consistent with its role in leptin signalling, Grb10 in AgRP and POMC neurons enhances the anorexic and weight-reducing actions of leptin. Grb10 also exaggerates the inhibitory effects of leptin on AgRP neurons via ATP-sensitive potassium channel-mediated currents while facilitating the excitatory drive of leptin on POMC neurons through transient receptor potential channels. Our study identifies Grb10 as a potent leptin sensitizer that contributes to the maintenance of energy homeostasis by enhancing the response of AgRP and POMC neurons to leptin.

Effects of indocyanine green fluorescence imaging of laparoscopic anatomic liver resection for HCC: a propensity score-matched study.

BACKGROUND: Recently, indocyanine green (ICG) fluorescence imaging has been increasingly used in laparoscopic anatomic liver resection. The aim of this study was to investigate the efficacy of ICG-guided laparoscopic anatomic liver resection in hepatocellular carcinoma (HCC) compared with traditional laparoscopic anatomic liver resection. METHODS: A retrospective study was performed on patients with pathologically diagnosed HCC who successfully underwent laparoscopic anatomical liver resection from January 2019 to December 2021. The outcomes were compared between the two groups before and after the propensity score matching (PSM). RESULTS: A total of 110 patients were included in this study, including 50 patients in the ICG-guided group and 60 patients in the traditional group. Compared with the traditional group, the ICG-guided group had a shorter operative duration (P = 0.040), less intraoperative blood loss (P = 0.044), a lower incidence of postoperative complications (P = 0.023), and a shorter postoperative hospitalisation (P < 0.001). After PSM, significant differences remained between the two groups for the duration of postoperative hospitalisation (P = 0.018) and postoperative complications (P = 0.042). There was no significant difference in the recurrence rate between the two groups before and after PSM. CONCLUSION: Laparoscopic anatomic liver resection guided by ICG fluorescence imaging can reduce the duration of postoperative hospitalisation for patients and the incidence of postoperative complications. However, it has no impact on the long-term outcome of patients.

Ominous Electrocardiographic Patterns in an Older Adult With Chest Pain.

This case report describes an older adult with a history of hypertension and diabetes with paroxysmal chest pain.

Clinical and electrocardiographic features in acute total left main coronary artery occlusion without collateral circulation.

BACKGROUNDS: Study concerning the clinical features, electrocardiogram (ECG) findings and outcomes in patients presenting with acute total occlusion of left main coronary artery (LM) without collateral circulation is limited. METHODS: 25 patients with acute total LM occlusion without collateral circulation by emergency coronary angiography, from muti-center registry, were retrospectively studied. The clinical and angiographic characteristics, ECG and in-hospital mortality were reviewed. RESULTS: Nineteen patients (76%) presented with cardiogenic shock. Twelve (60%, 12/20) patients had coronary slow flow or no reflow phenomenon after primary percutaneous coronary intervention (PCI). The in-hospital mortality rate was 88% (n = 22). All the patients presented with ST-segment elevation myocardial ischemia (STEMI) pattern, mostly involving leads I, aVL, V2, V3, V4, V5 and ST-segment depression in leads II, III and aVF. CONCLUSIONS: Acute total LM occlusion without collateral circulation portends high in-hospital mortality. Anterior ST elevation in the precordial leads from V2 to V4 through V6, and ST elevation in leads I and aVL, accompanying with ST depression in the inferior leads is associated with acute total LM occlusion without collateral circulation.

Application of Indocyanine Green Fluorescence Imaging Combined with Laparoscopic Ultrasound in Laparoscopic Microwave Ablation of Liver Cancer.

BACKGROUND The aim of this study was to assess the effect of indocyanine green (ICG) fluorescence imaging combined with laparoscopic ultrasound in laparoscopic microwave ablation of liver cancer. MATERIAL AND METHODS This study retrospectively analyzed 61 patients who underwent laparoscopic microwave ablation of liver cancer, including laparoscopic microwave ablation with and without ICG fluoroscopy. RESULTS The operative times, ablation times, postoperative hospital stay, postoperative complication rate, hospitalization cost, postoperative liver function changes, and postoperative overall survival were similar between the 2 groups, but there was a statistically significant difference in recurrence-free survival (P<0.05). A total of 5 lesions were found in the fluorescence laparoscopy group that were not found by preoperative imaging, while no new lesions were found in the ordinary laparoscopy group. Fluorescence laparoscopy has obvious advantages over ordinary laparoscopy in finding small lesions that were not found before surgery. In terms of complete ablation rate, 3 patients in the ordinary laparoscopy group and 1 patient in the fluorescence laparoscopy group were judged to be incompletely ablated and were ablated again at 1 month after the operation. CONCLUSIONS For small hepatocellular carcinoma with severe liver cirrhosis and located on the liver surface, fluorescence laparoscopy can better reveal the location and boundary of the tumor, and fluorescence laparoscopy can detect tiny lesions that cannot be detected by preoperative imaging. The combination of fluorescence laparoscopy and microwave ablation has a good effect on the treatment of small hepatocellular carcinoma located on the surface of the liver that is difficult to distinguish.

Revealing the mechanisms of the bioactive ingredients accumulation in Polygonatum cyrtonema by multiomics analyses.

Polygonatum cyrtonema is a medicinal and edible herb rich in polysaccharides, steroidal saponins, and flavonoids that has been widely used as a food, vegetable, and medicine over the years. Although previous studies have preliminarily explored the metabolic and transcriptional regulatory mechanisms of the main secondary metabolites in P. cyrtonema, the complex mechanism of microRNA (miRNA)-mediated posttranscriptional regulation remains unclear. Metabolome analysis showed that iso-ophiopogonanone B, (25S)-pratioside D1, disporopsin, and isodiosgenin-Glc-Glc, which are associated with intermediates in the flavonoids and saponins pathways, were significantly upregulated in the stem and leaf compared with the rhizome, and most saccharides, including arabinose, cellobiose, maltotetraose, and panose, showed the opposite trend, suggesting that they may contribute to the formation and accumulation of the main active ingredients in P. cyrtonema. We found that 4-hydroxymandelonitrile have a relatively good inhibitory effect on α-glucosidase, indicating that it may play a role in hypoglycemic functions. Transcriptome and weighted gene coexpression network analysis (WGCNA) were combined to reveal several candidate genes involved in the accumulation of polysaccharides, saponins, and flavonoids, including PcSQLE, PcCYP71A1, PcSUS, PcFK, and PcMYB102. Integrated analyses of miRNAs and messengerRNAs (mRNAs) showed that novel_miR14, novel_miR49, novel_miR75, and aof_miR164 were negatively correlated with alpha-linolenic acid metabolism and the mitogen activated protein kinase (MAPK) signaling pathway, including PcAOS, PcSPLA2, PcFRK1, and PcDELLA, indicating that these miRNAs may coordinately regulate the biosynthesis of other secondary metabolites in P. cyrtonema. These findings will facilitate in-depth research on the functions of these miRNAs and mRNAs related to the main active substances for pathological and biological regulation, which will be beneficial to provide theoretical guidance for the molecular breeding of P. cyrtonema.