Mitogenome-Based Phylogeny with Divergence Time Estimates Revealed the Presence of Cryptic Species within Heptageniidae (Insecta, Ephemeroptera).

Heptageniidae are known for their flat heads and bodies and are divided into three subfamilies. Despite the extensive diversity within this group and considerable efforts made to understand their evolutionary history, the internal classifications and origin time of Heptageniidae remains controversial. In this study, we newly sequenced 17 complete mitogenomes of Heptageniidae to reconstruct their phylogenetic positions within this family. Because of the ambiguous time of origin, our study also estimated the divergence time within Heptageniidae based on five fossil calibration points. The results of BI and ML trees all highly supported the monophyly of Heptageniidae and three subfamilies. The phylogenetic relationship of Rhithrogeninae + (Ecdyonurinae + Heptageniinae) was also recovered. The divergence time showed that Heptageniidae originated from 164.38 Mya (95% HPD, 150.23-181.53 Mya) in the mid-Jurassic, and Rhithrogeninae originated from 95.54 Mya (95% HPD, 73.86-120.19 Mya) in the mid-Cretaceous. Ecdyonurinae and Heptageniinae began to diverge at 90.08 Mya (95% HPD, 68.81-113.16 Mya) in the middle Cretaceous. After morphological identification, analysis of the mitogenome's composition, genetic distance calculation, phylogenetic analysis, and divergence time calculation, we suggest that two different populations of Epeorus montanus collected from Aksu, Xinjiang Uygur Autonomous Region (40°16' N, 80°26' E) and Xinyuan, Xinjiang Uygur Autonomous Region (43°20' N, 83°43' E) in China are cryptic species of E. montanus, but further detailed information on their morphological characteristics is needed to fully identify them.

Advances and challenges in neuroimaging-based pain biomarkers.

Identifying neural biomarkers of pain has long been a central theme in pain neuroscience. Here, we review the state-of-the-art candidates for neural biomarkers of acute and chronic pain. We classify these potential neural biomarkers into five categories based on the nature of their target variables, including neural biomarkers of (1) within-individual perception, (2) between-individual sensitivity, and (3) discriminability for acute pain, as well as (4) assessment and (5) prospective neural biomarkers for chronic pain. For each category, we provide a synthesized review of candidate biomarkers developed using neuroimaging techniques including functional magnetic resonance imaging (fMRI), structural magnetic resonance imaging (sMRI), and electroencephalography (EEG). We also discuss the conceptual and practical challenges in developing neural biomarkers of pain. Addressing these challenges, optimal biomarkers of pain can be developed to deepen our understanding of how the brain represents pain and ultimately help alleviate patients' suffering and improve their well-being.

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Nanyang Cattle.

The objective of this study was to determine the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, in Nanyang cattle after a single intravenous (IV), and intramuscular (IM) administration of enrofloxacin at 2.5 mg/kg body weight (BW). Blood samples were collected at predetermined time points. Enrofloxacin and ciprofloxacin concentrations in plasma were simultaneously determined using a high-performance liquid chromatography (HPLC) assay method and subjected to a non-compartmental analysis. After IV administration, enrofloxacin had a mean (±SD) volume of distribution at steady state (VSS) of 1.394 ± 0.349 L/kg, a terminal half-life (t1/2λz) of 3.592 ± 1.205 h, and a total body clearance (Cl) of 0.675 ± 0.16 L/h/kg. After IM administration, enrofloxacin was absorbed relatively slowly but completely, with a mean absorption time (MAT) of 6.051 ± 1.107 h and a bioavailability of 99.225 ± 7.389%. Both compounds were detected simultaneously in most plasma samples following both routes of administration, indicating efficient biotransformation of enrofloxacin to ciprofloxacin. After IV injection, the peak concentration (Cmax) of ciprofloxacin was 0.315 ± 0.017 µg/mL, observed at 0.958 ± 0.102 h. Following IM injection, the corresponding values were 0.071 ± 0.006 µg/mL and 3 ± 1.095 h, respectively. Following IV and IM administration, the conversion ratio of enrofloxacin to ciprofloxacin was calculated as 59.2 ± 9.6% and 31.2 ± 7.7%, respectively. The present results demonstrated favorable pharmacokinetic profiles for enrofloxacin, characterized by complete absorption with relatively slow kinetics, extensive distribution, efficient biotransformation to ciprofloxacin, and prolonged elimination in Nanyang cattle.

Unlocking multi-photon excited luminescence in pyrazolate trinuclear gold clusters for dynamic cell imaging.

The family of coinage-metal-based cyclic trinuclear complexes exhibits abundant photophysical properties, promising for diverse applications. However, their utility in biochemistry is often hindered by large particle size and strong hydrophobicity. Meanwhile, the investigation into multi-photon excited luminescence within this family remained undocumented, limiting their potential in bio-imaging. Herein, we unveil the multi-photon excited luminescent properties of pyrazolate-based trinuclear gold(I) clusters, facilitated by excimeric gold(I)···gold(I) interactions, revealing a nonlinear optical phenomenon within this family. Furthermore, to address issues of poor biocompatibility, we employ electrospinning coupled with hydroxypropyl-beta-cyclodextrin as the matrix to fabricate a flexible, durable, transparent, and red emissive film with a photoluminescence quantum yield as high as 88.3%. This strategy not only produces the film with sufficient hydrophilicity and stability, but also achieves the downsizing of trinuclear gold(I) clusters from microscale to nanoscale. Following the instantaneous dissolution of the film in the media, the released trinuclear gold(I) nanoparticles have illuminated cells and bacteria through a real-time, non-toxic, multi-photon bio-imaging approach. This achievement offers a fresh approach for utilizing coinage-metal-based cyclic trinuclear complexes in biochemical fields.

Comparison of reperfusion- and central repair-first strategies for acute type a dissection with mesenteric malperfusion: a single-center retrospective cohort study.

BACKGROUND: We seek to compare the early and late outcomes of reperfusion-first versus central repair-first strategies in patients with acute type A dissection (ATAAD) complicated by mesenteric malperfusion. METHODS: Among 68 patients, reperfusion-first strategy with superior mesenteric artery (SMA) stenting was adopted in 31 and central repair-first in 37, based on rupture risk and circulatory compromise, severity, time and mechanisms of mesenteric ischemia. Early and late outcomes were compared between two strategies. Follow-up was 100% at 3.3±1.4 years. RESULTS: Mean age was 50.6±11.4 years (59 males, 86.8%). The reperfusion-first group had more celiac artery involvement (74.2% vs. 48.6%) and peritoneal irritation signs (19.4% vs. 2.7%), while central repair-first group had more tamponade (27% vs. 3.2%). Early mortality was 48.6% (18/37) with central repair-first strategy versus 19.4% (6/31) in reperfusion-first group (P=0.012). Reperfusion-first patients had fewer gastrointestinal complications (12.9% vs. 54.1%, P<0.001) and respiratory failure (3.2% vs. 24.3%, P=0.017). At 5 years, SMA stent patency was 84%, and survival was significantly higher in reperfusion-first patients (80.6% vs. 45.9%, P=0.009), with similar freedom from adverse events between two groups (74.9% vs. 76.0%, P=0.812). Tamponade (hazard ratio [HR], 3.093; P=0.023), peritoneal irritation signs (HR, 8.559; P=0.006), and lactate (mmol/L) (HR, 1.279; P<0.001) were predictors for all-cause mortality. CONCLUSIONS: In this series of ATAAD patients with mesenteric malperfusion, the reperfusion-first strategy with SMA stenting could significantly reduce the mortality risk and achieved favorable late survival and freedom from adverse events. These results argue favorably for the use of the reperfusion-first strategy in such patients.

Comparative Mitogenome of Phylogenetic Relationships and Divergence Time Analysis within Potamanthidae (Insecta: Ephemeroptera).

Potamanthidae belongs to the superfamily Ephemeroidea but has no complete mt genome released in the NCBI (except for two unchecked and one partial mt genome). Since the sister clade to Potamanthidae has always been controversial, we sequenced seven mt genomes of Potamanthidae (two species from Rhoenanthus and five species from Potamanthus) in order to rebuild the phylogenetic relationships of Potamanthidae in this study. The divergence time of Potamanthidae was also investigated by utilizing five fossil calibration points because of the indeterminate origin time. In addition, because Rhoenanthus coreanus and Potamanthus luteus are always in low-temperature environments, we aimed to explore whether these two species were under positive selection at the mt genome level. Amongst the 13 PCGs, CGA was used as the start codon in COX1, whereas other genes conformed to initiating with an ATN start codon. From this analysis, UUA (L), AUU (I), and UUU (F) had the highest usage. Furthermore, the DHU arm was absent in the secondary structure of S1 in all species. By combining the 13 PCGs and 2 rRNAs, we reconstructed the phylogenetic relationship of Potamanthidae within Ephemeroptera. The monophyly of Potamanthidae and the monophyly of Rhoenanthus and Potamanthus were supported in the results. The phylogenetic relationship of Potamanthidae + (Ephemeridae + Polymitarcyidae) was also recovered with a high prior probability. The divergence times of Potamanthidae were traced to be 90.44 Mya (95% HPD, 62.80-121.74 Mya), and the divergence times of Rhoenanthus and Potamanthus originated at approximately 64.77 Mya (95% HPD, 43.82-88.68 Mya), thus belonging to the late Pliocene Epoch or early Miocene Epoch. In addition, the data indicated that R. coreanus was under negative selection and that ATP8 and ND2 in Potamanthidae had a high evolutionary rate.

Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.

First Family Case of Hemoglobinopathy Titusville in China with Falsely Low SpO2 and Unmeasurable SaO2.

BACKGROUND: Normal hemoglobin is a tetrameric structure, consisting of two alpha-globin chains and two nonalpha (beta, gamma, delta) chains. Hemoglobinopathies occur when the presence of gene mutations affect the molecular structure or expression of the globin chains. METHODS: We reported the case of a 9-year-old Chinese girl who presented with abnormal low oxygen saturation values on pulse oximetry and no oximetry results were obtained during blood gas analysis (BGA). RESULTS: High-performance liquid chromatography (HPLC) and capillary electrophoresis demonstrated that the presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin Titusville, was proven by gene sequencing. The patient's mother and aunt also carry the hemoglobin variant, representing the first Chinese family case reported. CONCLUSIONS: Hemoglobin Titusville is a rare genetic hemoglobin structural defect. early diagnosis can help patients and clinicians avoid unnecessary anxiety and costly or excessive clinical investigations.

Bergenin Alleviates Ulcerative Colitis By Decreasing Gut Commensal Bacteroides vulgatus-Mediated Elevated Branched-Chain Amino Acids.

Ulcerative colitis is closely associated with the dysregulation of gut microbiota. There is growing evidence that natural products may improve ulcerative colitis by regulating the gut microbiota. In this research, we demonstrated that bergenin, a naturally occurring isocoumarin, significantly ameliorates colitis symptoms in dextran sulfate sodium (DSS)-induced mice. Transcriptomic analysis and Caco-2 cell assays revealed that bergenin could ameliorate ulcerative colitis by inhibiting TLR4 and regulating NF-κB and mTOR phosphorylation. 16S rRNA sequencing and metabolomics analyses revealed that bergenin could improve gut microbiota dysbiosis by decreasing branched-chain amino acid (BCAA) levels. BCAA intervention mediated the mTOR/p70S6K signaling pathway to exacerbate the symptoms of ulcerative colitis in mice. Notably, bergenin greatly decreased the symbiotic bacteria Bacteroides vulgatus (B. vulgatus), and the gavage of B. vulgatus increased BCAA concentrations and aggravated the symptoms of ulcerative colitis in mice. Our findings suggest that gut microbiota-mediated BCAA metabolism plays a vital role in the protective effect of bergenin on ulcerative colitis, providing novel insights for ulcerative colitis prevention through manipulation of the gut microbiota.

Effect of triggering receptor expressed on myeloid cells 2-associated alterations on lipid metabolism in macrophages in the development of non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Triggering receptor expressed on myeloid cells 2 (TREM2) plays crucial roles in metabolic homeostasis and inflammatory response. Altered metabolic function in macrophages could modulate their activation and immune phenotype. The present study aimed to investigate the expression of TREM2 in non-alcoholic fatty liver disease (NAFLD) and to clarify the underlying mechanism of TREM2 on macrophages lipid metabolism and oxidative stress. METHODS: Hepatic TREM2 expression and its relationship with NAFLD progression were analyzed in patients with NAFLD and mice fed a high-fat diet. Lipid metabolism and oxidative stress were investigated in macrophages from NAFLD mice or stimulated with saturated fatty acids. Knockdown and overexpression of TREM2 were further explored. RESULTS: Triggering receptor expressed on myeloid cells 2+ macrophages were increased along with NAFLD development, characterized by aggravated steatosis and liver damage in humans and mice. TREM2 expression was upregulated and lipid metabolism was changed in macrophages from NAFLD mice or metabolically activated by saturated fatty acid in vitro, as demonstrated by increased lipid uptake and catabolism, but reduced de novo synthesis of fatty acids (FAs). Regulation of TREM2 expression in lipid-laden macrophages reprogrammed lipid metabolism, especially the fatty acid oxidation capacity of mitochondria. TREM2 knockdown promoted oxidative stress by aggravating FAs deposition in mitochondria. Intervention of mitochondrial FAs transport in lipid-laden macrophages alleviated FA deposition and reactive oxygen species production induced by TREM2 knockdown. CONCLUSIONS: Triggering receptor expressed on myeloid cells 2 expression was associated with the lipid metabolic profile and reactive oxygen species production in macrophages. High expression of TREM2 in macrophages may protect the liver from oxidative stress in NAFLD.

Ethyl acetate extract of Terminalia chebula alleviates DSS-induced ulcerative colitis in C57BL/6 mice.

Background: The Chinese pharmacopeia records Terminalia chebula as effective in treating prolonged diarrhea and dysentery, blood in the stool, and prolapse. Modern pharmacological research proves it has multiple pharmacological benefits, including antioxidant, anti-inflammatory, analgesic, hepatoprotective, neuroprotective, and other properties. Objectives: This study aims to clarify the role of Terminalia chebula's ethyl acetate extract (TCEA) on ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice, as well as explore the potential mechanism of action. Materials and methods: The variation of different extracts of T. chebula was detected using the HPLC technique, and the main components in TCEA were identified. DSS was used to establish a mouse model to mimic the physiological state of UC in humans; the alleviating effect of TCEA and positive control 5-ASA on UC mice were evaluated by gavage treatment. Disease progression was assessed by monitoring the mouse's weight change and disease activity index (DAI). The changes in colon tissue were estimated by measuring colon length, HE, and AB-PAS staining and detecting oxidative stress parameters. The results draw from Western blot and real-time PCR showed the TLR4/MyD88/NF-κB pathway may involve in the anti-inflammatory activity of TCEA. Furthermore, the gut flora sequencing technique was employed to monitor the differentiation of intestinal microbiota of mice induced by DSS and TCEA treatment. Results: TCEA significantly lowered DAI scores and inhibited the weight loss and colonic shortening induced by DSS. The colon histomorphology and oxidative stress levels were enhanced after TCEA treatment compared with DSS induced UC group. TCEA attenuated the inflammatory response by regulating TLR4/MyD88/NF-κB pathway activation. Intestinal flora sequencing showed that DSS and TCEA greatly impacted mice's composition and diversity of intestinal microorganisms. But TCEA increased the abundance of Bacteroidetes and decreased the abundance of Firmicutes and Proteobacteria compared with the DSS group, which contributed a lot to returning the intestinal flora to a balanced state. Conclusion: This study confirms the alleviating effect of TCEA on UC and provides new ideas for developing TCEA into a new drug to treat UC.

Parallel detection of multiple zoonotic parasites using a real-time fluorogenic loop-mediated isothermal amplification-based quadruple-sample microfluidic chip.

Zoonotic parasites pose significant health risks globally. In the present study, we combined a microfluidic chip with loop-mediated isothermal amplification (on-chip LAMP) to detect five zoonotic parasites: Toxoplasma gondii, Cryptosporidium parvum, Cryptosporidium hominis, Clonorchis sinensis, and Taenia solium. This method enabled the simultaneous parallel analysis of five genetic markers from a maximum of four samples per chip. The on-chip LAMP assay was conducted in a highly automated format via the addition (by pipetting) of each sample in a single operation. The reaction was performed in volumes as low as 5 µL at a temperature of 65°C for 60 min, achieving limits of detection ranging from 10-2 to 10-3 pg./µL of recombinant plasmid DNA. All the time-to-positive values were less than 40 min, and almost all the coefficients of variation were less than 10%, even when using limit of detection concentrations for multiple pathogens, indicating robust reproducibility among replicates. The clinical sensitivity and specificity for detecting 135 field samples were 98.08 and 97.59%, respectively, compared with traditional biological methods, indicating good applicability in the detection of field samples. This on-chip LAMP assay allows for low reagent consumption, ease of operation, and multiple analyses of samples and genetic targets, and is applicable for on-site detection and the routine monitoring of multiple zoonotic parasites.

Colchicine protects against the development of experimental abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA is life-threatening. Colchicine is a medicine used to treat gout and familial Mediterranean fever, and recently, it was approved to reduce the risk of cardiovascular events in adult patients with established atherosclerotic disease. With an AAA mice model created by treatment with porcine pancreatic elastase (PPE) and ß-aminopropionitrile (BAPN), this work was designed to explore whether colchicine could protect against the development of AAA. Here, we showed that colchicine could limit AAA formation, as evidenced by the decreased total aortic weight per body weight, AAA incidence, maximal abdominal aortic diameter and collagen deposition. We also found that colchicine could prevent the phenotypic switching of vascular smooth muscle cells from a contractile to synthetic state during AAA. In addition, it was demonstrated that colchicine was able to reduce vascular inflammation, oxidative stress, cell pyroptosis and immune cells infiltration to the aortic wall in the AAA mice model. Finally, it was proved that the protective action of colchicine against AAA formation was mainly mediated by preventing immune cells infiltration to the aortic wall. In summary, our findings demonstrated that colchicine could protect against the development of experimental AAA, providing a potential therapeutic strategy for AAA intervention in the clinic.

Terminalia bellirica Fruit Extract Alleviates DSS-Induced Ulcerative Colitis by Regulating Gut Microbiota, Inflammatory Mediators, and Cytokines.

Ulcerative colitis (UC) is a chronic inflammatory disease significantly impacting patients' lives. This study aimed to elucidate the alleviating effect of ethyl acetate extract (TBEA) from Terminalia bellirica fruit on UC and to explore its mechanism. TBEA was the fraction with the best anti-inflammatory activity screened using in vitro anti-inflammatory assays, and HPLC initially characterized its composition. The mice model of ulcerative colitis was established after free drinking of 2.5% dextran sulfate sodium for six days, and the experimental group was treated with 50 mg/kg and 100 mg/kg TBEA for seven days. We found that TBEA significantly alleviated symptoms in UC mice, including a physiologically significant reduction in disease activity index and pathological damage to colonic tissue. TBEA dramatically slowed down oxidative stress and inflammatory process in UC mice, as evidenced by decreasing myeloperoxidase and malondialdehyde activities and increasing glutathione and catalase levels by reducing the concentrations of IL-6, IL-1ß, TNF-α, and NO in UC mice, as well as by regulating key proteins in the IL-6/JAK2/STAT3 pathway. Meanwhile, TBEA maintained intestinal homeostasis by regulating intestinal flora structure. Our study provides new ideas for developing TBEA into a new drug to treat UC.

Plant Exosome-like Nanovesicles and Their Role in the Innovative Delivery of RNA Therapeutics.

Exosomes are single membrane-bound spheres released from cells carrying complex cargoes, including lipids, proteins, and nucleic acids. Exosomes transfer specific cargoes from donor to acceptor cells, playing important roles in cell-to-cell communication. Current studies have reported that plant exosomes are prominent in transferring small RNA between host and pathogens in a cross-kingdom manner. Plant exosomes are excellent RNA interference (RNAi) delivery agents with similar physical and chemical properties to mammalian exosomes and have potential applications in therapeutic delivery systems. Recent data have suggested that plant exosome-like nanovesicles (PENVs) and artificial PENV-derived nano-vectors (APNVs) are beneficial for delivering therapeutic small RNA in mammalian systems and exhibit excellent competitiveness in future clinical applications. This review features their preparation methods, composition, roles in small RNA delivery for health functionalities, and their potency as functional nanomedicine.

Endoscopic Endonasal Approach for Trigeminal Schwannomas: Tailored Approaches Based on Lesion Traits.

OBJECTIVES: To describe four endoscopic endonasal subapproaches, namely, the trans-lamina papyracea, trans-prelacrimal recess, trans-Meckel's cave, and transclival approaches for trigeminal schwannomas (TSs). METHODS: This retrospective study reviewed the medical records and intraoperative videos of 38 patients with TSs who underwent endoscopic endonasal approach (EEA) between Jan 2013 and Dec 2021. RESULTS: According to Jeong's classification, for TS equally in middle and posterior fossae (MP), a purely trans-Meckel's cave approach was carried out in 2 cases, and a combined transclival approach was carried out in 4 cases. The four tumors that involved infratemporal fossa (two E3, one mE3, and one Mpe3) were performed via a trans-prelacrimal recess approach, and type Mpe3 was also assisted by the trans-Meckel's cave approach. One patient with type E1 was treated with a trans-lamina papyracea approach. The other 27 cases, including type M, Mp, ME2, and MpE2, were all removed by a purely trans-Meckel's cave approach. Thirty-six patients (97.4%) received total resection under a purely EEA. The functional abilities and preoperative symptoms of 31 patients (88.6%) improved. Eight (21.1%) patients experienced permanent neurological function deficits. Postoperative cerebrospinal fluid and intraoperative internal carotid artery injury occurred in 1 (2.6%) patient. CONCLUSION: According to the specific endoscopic endonasal subapproaches corresponding to the different TS locations, satisfactory results can be obtained for most types of tumors. It represents an effective alternative to the open transcranial approach and can also be properly used in most types of TS with experienced hands. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2564-2571, 2023.

Inhibiting neuronal AC1 for treating anxiety and headache in the animal model of migraine.

Migraines are a common medical condition. From a basic science point of view, the central mechanism for migraine and headache is largely unknown. In the present study, we demonstrate that cortical excitatory transmission is significantly enhanced in the anterior cingulate cortex (ACC)-a brain region which is critical for pain perception. Biochemical studies found that the phosphorylation levels of both the NMDA receptor GluN2B and AMPA receptor GluA1 were enhanced in ACC of migraine rats. Both the presynaptic release of glutamate and postsynaptic responses of AMPA receptors and NMDA receptors were enhanced. Synaptic long-term potentiation (LTP) was occluded. Furthermore, behavioral anxiety and nociceptive responses were increased, which were reversed by application of AC1 inhibitor NB001 within ACC. Our results provide strong evidence that cortical LTPs contribute to migraine-related pain and anxiety. Drugs that inhibit cortical excitation such as NB001 may serve as potential medicines for treating migraine in the future.

In situ subtotal spleen resection combined with selective pericardial devascularization for the treatment of portal hypertension.

BACKGROUND: Hypersplenism and esophageal varices bleeding are the major complications of portal hypertension (PHT). In recent years, increasing attention has been given to spleen preservation operations. The mode and long-term effects of subtotal splenectomy and selective pericardial devascularization for PHT remain controversial. AIM: To investigate the clinical efficacy and safety of subtotal splenectomy combined with selective pericardial devascularization for the treatment of PHT. METHODS: This was a retrospective study of 15 patients with PHT who underwent subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization in the Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University from February 2011 to April 2022. Fifteen propensity score-matched patients with PHT who underwent total splenectomy at the same time served as the control group. The patients were followed for up to 11 years after surgery. We compared the postoperative platelet levels, perioperative splenic vein thrombosis, and serum immunoglobulin levels between the two groups. Abdominal enhanced computed tomography was used to evaluate the blood supply and function of the residual spleen. The operation time, intraoperative blood loss, evacuation time, and hospital stay were compared between the two groups. RESULTS: The postoperative platelet level of patients in the subtotal splenectomy group was significantly lower than that in the total splenectomy group (P < 0.05), and the postoperative portal system thrombosis rate in the subtotal splenectomy group was also much lower than that in the total splenectomy group. The levels of serum immunoglobulins (IgG, IgA, and IgM) showed no significant differences after surgery compared with before surgery in the subtotal splenectomy group (P > 0.05), but serum immunoglobulin IgG and IgM levels decreased dramatically after total splenectomy (P < 0.05). The operation time in the subtotal splenectomy group was longer than that in the total splenectomy group (P < 0.05), but there were no significant differences in the amount of intraoperative blood loss, evacuation time, or hospital stay between the two groups. CONCLUSION: Subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization is a safe and effective surgical treatment for patients with PHT, not only correcting hypersplenism but also preserving splenic function, especially immunological function.

Natamycin Has an Inhibitory Effect on Neofusicoccum parvum, the Pathogen of Chestnuts.

This research aimed to investigate natamycin's antifungal effect and its mechanism against the chestnut pathogen Neofusicoccum parvum. Natamycin's inhibitory effects on N. parvum were investigated using a drug-containing plate culture method and an in vivo assay in chestnuts and shell buckets. The antifungal mechanism of action of natamycin on N. parvum was investigated by conducting staining experiments of the fungal cell wall and cell membrane. Natamycin had a minimum inhibitory concentration (MIC) of 100 µg/mL and a minimum fungicidal concentration (MFC) of 200 µg/mL against N. parvum. At five times the MFC, natamycin had a strong antifungal effect on chestnuts in vivo, and it effectively reduced morbidity and extended the storage period. The cell membrane was the primary target of natamycin action against N. parvum. Natamycin inhibits ergosterol synthesis, disrupts cell membranes, and causes intracellular protein, nucleic acid, and other macromolecule leakages. Furthermore, natamycin can cause oxidative damage to the fungus, as evidenced by decreased superoxide dismutase and catalase enzyme activity. Natamycin exerts a strong antifungal effect on the pathogenic fungus N. parvum from chestnuts, mainly through the disruption of fungal cell membranes.