Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Neural network analysis of pharyngeal sounds can detect obstructive upper respiratory disease in brachycephalic dogs.

Brachycephalic obstructive airway syndrome (BOAS) is a highly prevalent respiratory disease affecting popular short-faced dog breeds such as Pugs and French bulldogs. BOAS causes significant morbidity, leading to poor exercise tolerance, sleep disorders and a shortened lifespan. Despite its severity, the disease is commonly missed by owners or disregarded by veterinary practitioners. A key clinical sign of BOAS is stertor, a low-frequency snoring sound. In recent years, a functional grading scheme has been introduced to semi-objectively grade BOAS based on the presence of stertor and other abnormal signs. However, correctly grading stertor requires significant experience and adding an objective component would aid accuracy and repeatability. This study proposes a recurrent neural network model to automatically detect and grade stertor in laryngeal electronic stethoscope recordings. The model is developed using a novel dataset of 665 labelled recordings taken from 341 dogs with diverse BOAS clinical signs. Evaluated via nested cross validation, the neural network predicts the presence of clinically significant BOAS with an area under the receiving operating characteristic of 0.85, an operating sensitivity of 71% and a specificity of 86%. The algorithm could enable widespread screening for BOAS to be conducted by both owners and veterinarians, improving treatment and breeding decisions.

The Clinical Impact of Different Types of Preoperative Biliary Intervention on Postoperative Biliary Tract Infection of Patients Undergoing Pancreaticoduodenectomy.

Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated.

Candidate membrane protein gene families related to chemoreception in a wood-boring beetle, Pharsalia antennata Gahan (Coleoptera: Cerambycidae).

The longhorned beetles are key players for the maintenance of biodiversity in the terrestrial ecosystem. As xylophagous cerambycid insects in Coleoptera, the beetles have evolved specialized olfactory and gustatory systems to recognize chemical cues in the surrounding habitats. Despite over 36,000 described species in the Cerambycidae family including a wood-boring pest Pharsalia antennata, only a limited number of them (<1 %) have been characterized regarding their chemical ecology at the molecular level. Here, we surveyed four membrane protein gene families in P. antennata related to chemoreception through transcriptomics, phylogenetics and expression profiling analyses. In total, 144 genes encoding 72 odorant receptors (ORs), 33 gustatory receptors (GRs), 23 ionotropic receptors (IRs), four sensory neuron membrane proteins (SNMPs) and 12 ionotropic glutamate receptors (iGluRs) were harvested from the transcriptome of multiple tissues including antennae and legs of both sexes. The lineage-specific expansion of PantORs possibly implied a diverse range of host plants in this beetle, supporting this correlation between the host range and olfactory receptor repertoire sizes across cerambycid species. Further phylogenetic analysis revealed that Group 2 was contributed mainly to the large OR gene repertoire in P. antennata, representing 18 genes in Group 2A and eight in Group 2B. On the other hand, some key chemosensory genes were identified by applying a phylogenetics approach, such as PantOR21 close to the 2-phenylethanol receptor in Megacyllene caryae, three carbon dioxide GRs and seven Antennal IRs (A-IRs) clades. We also determined sex- and tissue-specific expression profiles of 69 chemosensory genes, revealing the high expression of most PantORs in antennae. Noticeably, 10 sex-biased genes (six PantORs, three PantIRs and PantSNMP1a) were presented in antennae, five sex-biased PantGRs in legs and 39 sex-biased genes (15 PantORs, 13 PantGRs, eight PantIRs and three PantSNMPs) in abdomens. These findings have greatly enhanced our knowledge about the chemical ecology of P. antennata and identify candidate molecular targets for mediating smell and taste of this beetle.

CRISPR/Cas9-mediated ebony knockout causes melanin pigmentation and prevents moth Eclosion in Ectropis grisescens.

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive tea pest in China. Mimesis, characterized by changing body color, is an important trait of E. grisescens larvae. Hence, identifying melanin pathway-related genes may contribute to developing new pest control strategies. In the present study, we cloned Egebony, a gene potentially involved in melanin pigmentation in E. grisescens, and subsequently conducted CRISPR/Cas9-mediated targeted mutagenesis of Egebony to analyze its role in pigmentation and development. At the larvae, prepupae, and pupae stages, Egebony-knockout individuals exhibited darker pigmentation than the wild-type. However, Egebony knockout did not impact the colors of sclerotized appendants, including ocelli, setae, and claws. While mutant pupae could successfully develop into moths, they were unable to emerge from the puparium. Notably, embryo hatchability and larval survival of mutants remained normal. Further investigation indicated that mutant pupae exhibited significantly stronger shearing force than the wild-type, with the pigmented layer of mutant pupae appearing darker and thicker. Collectively, these results suggest that the loss of Egebony might increase the rigidity of the puparium and prevent moth eclosion. This study provides new insights into understanding the function and diversification of ebony in insect development and identifies a lethal gene that can be manipulated for developing effective pest control strategies.

Three chemosensory proteins enriched in antennae and tarsi of Rhaphuma horsfieldi differentially contribute to the binding of insecticides.

Antennae and legs (primarily the tarsal segments) of insects are the foremost sensory organs that contact a diverse range of toxic chemicals including insecticides. Binding proteins expressed in the two tissues are potential molecular candidates serving as the binding and sequestering of insecticides, like chemosensory proteins (CSPs). Insect CSPs endowed with multiple roles have been suggested to participate in insecticide resistance, focusing mainly on moths, aphids and mosquitos. Yet, the molecular underpinnings underlying the interactions of cerambycid CSPs and insecticides remain unexplored. Here, we present binding properties of three antenna- and tarsus-enriched RhorCSPs (RhorCSP1, CSP2 and CSP3) in Rhaphuma horsfieldi to eight insecticide classes totaling 15 chemicals. From the transcriptome of this beetle, totally 16 CSP-coding genes were found, with seven full-length sequences. In phylogeny, these RhorCSPs were distributed dispersedly in different clades. Expression profiles revealed the abundant expression of RhorCSP1, CSP2 and CSP3 in antennae and tarsi, thus as representatives for studying the protein-insecticide interactions. Binding assays showed that the three RhorCSPs were tuned differentially to insecticides but exhibited the highest affinities with hexaflumuron, chlorpyrifos and rotenone (dissociation constants <13 µM). In particular, RhorCSP3 could interact strongly with 10 of tested insecticides, of which four residues (Tyr25, Phe42, Val65 and Phe68) contributed significantly to the binding of six, four, three and four ligands, respectively. Of these, the binding of four mutated RhorCSP3s to a botanical insecticide rotenone was significantly weakened compared to the wildtype protein. Furthermore, we also evidenced that RhorCSP3 was a broadly-tuned carrier protein in response to a wide variety of plant odorants outside insecticides. Altogether, our findings shed light on different binding mechanisms and odorant-tuning profiles of three RhorCSPs in R. horsfieldi and identify key residues of the RhorCSP3-insecticide interactions.

Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation.

Type 2 diabetes mellitus (T2DM) patients exhibit greater susceptibility to vascular calcification (VC), which has a higher risk of death and disability. However, there is no specific drug for VC therapy. NLRP3 inflammasome activation as a hallmark event of medial calcification leads to arterial stiffness, causing vasoconstrictive dysfunction in T2DM. Empagliflozin (EMPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), restrains hyperglycemia with definite cardiovascular benefits. Given the anti-inflammatory activity of EMPA, herein we investigated whether EMPA protected against VC in the aorta of T2DM mice by inhibiting NLRP3 inflammasome activation. Since db/db mice receiving a normal diet developed VC at the age of about 20 weeks, we administered EMPA (5, 10, 20 mg·kg-1·d-1, i.g) to 8 week-old db/db mice for 12 weeks. We showed that EMPA intervention dose-dependently ameliorated the calcium deposition, accompanied by reduced expression of RUNX2 and BMP2 proteins in the aortas. We found that EMPA (10 mg·kg-1·d-1 for 6 weeks) also protected against VC in vitamin D3-overloaded mice, suggesting the protective effects independent of metabolism. We showed that EMPA (10 mg·kg-1·d-1) inhibited the abnormal activation of NLRP3 inflammasome in aortic smooth muscle layer of db/db mice. Knockout (KO) of NLRP3 significantly alleviated VC in STZ-induced diabetic mice. The protective effects of EMPA were verified in high glucose (HG)-treated mouse aortic smooth muscle cells (MOVASs). In HG-treated NLRP3 KO MOVASs, EMPA (1 µM) did not cause further improvement. Bioinformatics and Western blot analysis revealed that EMPA significantly increased the expression levels of basic helix-loop-helix family transcription factor e40 (Bhlhe40) in HG-treated MOVASs, which served as a negative transcription factor directly binding to the promotor of Nlrp3. We conclude that EMPA ameliorates VC by inhibiting Bhlhe40-dpendent NLRP3 inflammasome activation. These results might provide potential significance for EMPA in VC therapy of T2DM patients.

The supplementation of Rothia as a potential preventive approach for bone loss in mice with ovariectomy-induced osteoporosis.

There is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of Rothia on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 µL/d) gavage of Rothia was performed for 8 weeks starting from 1 week after OVX. Microcomputed tomography was used to analyze the bone mass and bone microstructure of mice in each group after sacrifice. Histological staining and immunohistochemistry were then applied to identify the expression of pro-inflammatory cytokines, intestinal permeability, and osteogenic and osteoclastic activities of mice. The collected feces of mice in each group were used for 16S rRNA high-throughput sequencing to detect the alterations in composition, abundance, and diversity of gut microbiota. This study demonstrated that the gavage of Rothia alleviated bone loss in mice with OVX-induced osteoporosis, improved OVX-induced intestinal mucosal barrier injury, optimized intestinal permeability (zonula occludens protein 1 and occludin), reduced intestinal inflammation (tumor necrosis factor-α and interleukin-1ß), and regulated imbalance of gut microbiota. Based on "gut-bone" axis, this study revealed that regular and quantitative gavage of Rothia can relieve bone loss in mice with OVX-induced osteoporosis by repairing the intestinal mucosal barrier injury, optimizing the intestinal permeability, inhibiting the release of pro-inflammatory cytokines, and improving the disorder of gut microbiota.

Lonicera japonica protects Pelodiscus sinensis by inhibiting the biofilm formation of Aeromonas hydrophila.

Aquaculture has suffered significant financial losses as a result of the infection of zoonotic Aeromonas hydrophila, which has a high level of resistance to classic antibiotics. In this study, we isolated an A. hydrophila strain B3 from diseased soft-shelled turtle (Pelodiscus sinensis), which is one of the most commercially significant freshwater farmed reptiles in East Asia, and found that A. hydrophila was its dominant pathogen. To better understand the inhibition effect and action mechanism of Chinese herbs on A. hydrophila, we conducted Chinese herbs screening and found that Lonicera japonica had a significant antibacterial effect on A. hydrophila B3. Experimental therapeutics of L. japonica on soft-shelled turtle showed that the supplement of 1% L. japonica to diet could significantly upregulate the immunity-related gene expression of soft-shelled turtle and protect soft-shelled turtle against A. hydrophila infection. Histopathological section results validated the protective effect of L. japonica. As the major effective component of L. japonica, chlorogenic acid demonstrated significant inhibitory effect on the growth of A. hydrophila with MIC at 6.4 mg/mL. The in vitro assay suggested that chlorogenic acid could inhibit the hemolysin/protease production and biofilm formation of A. hydrophila and significantly decrease the expression of quorum sensing, biofilm formation, and hemolysin-related genes in A. hydrophila. Our results showed that the Chinese herb L. japonica would be a promising candidate for the treatment of A. hydrophila infections in aquaculture, and it not only improves the immune response of aquatic animals but also inhibits the virulence factor (such as biofilm formation) expression of A. hydrophila. KEY POINTS: • A. hydrophila was the dominant pathogen of the diseased soft-shelled turtle. • L. japonica can protect soft-shelled turtle against A. hydrophila infection. • Chlorogenic acid inhibits the growth and biofilm formation of A. hydrophila.

Comparison of the effectiveness of three different rhinoplasty techniques to correct stenotic nostrils using silicone models: A case study.

OBJECTIVE: To compare the effects of three different rhinoplasty techniques on the postoperative cross-sectional areas (CSAs) of the nares and nasal vestibuli. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Ninety-nine 3D-printed, remolded silicone models of a single French bulldog's rostral nose. METHODS: Models were fabricated based on a computed tomographic (CT) scan of the nose of a French bulldog with moderately stenotic nares. Each model underwent either vertical wedge resection (VW), modified horizontal wedge resection (MHW), or ala-vestibuloplasty (AVP) performed by a single surgeon (n = 33 per group). Preoperative and postoperative CT scans of the models were performed, and CSAs of the airway from the nares to the caudal end of the nasal vestibules were calculated. RESULTS: All three rhinoplasty techniques increased CSAs (adjusted p values <.001) but to different levels caudally within the nasal vestibule. Vertical wedge resection achieved this up to the start of the alar fold, MHW up to halfway between the nares and the alar fold and AVP up to the caudal nasal vestibule. Average percentage increases in CSA were 26%, 15% and 74%, respectively. Ala-vestibuloplasty led to larger CSAs than VW and MHW from the nares to the caudal nasal vestibule (adjusted p values <.05). The proportional difference within each technique was <7%. CONCLUSION: Ala-vestibuloplasty resulted in a larger increase in the airway CSA of silicone modeled nares and nasal vestibules of a single French bulldog in comparison with VW and MHW. CLINICAL SIGNIFICANCE: Ala-vestibuloplasty can be considered for French bulldogs with moderately stenotic nares and evidence of nasal vestibular stenosis.

Comparative transcriptomics reveals the conservation and divergence of reproductive genes across three sympatric Tomicus bark beetles.

Three tree-killing bark beetles belonging to the genus Tomicus, Tomicus yunnanensis, Tomicus brevipilosus and Tomicus minor (Coleoptera; Curculionidae, Scolytinae), are serious wood-borers with larvae feeding on the phloem tissues of Pinus yunnanensis. The three Tomicus beetles, in some cases, coexist in a same habitat, providing a best system for exploring the conservation and divergence of reproductive genes. Here, we applied comparative transcriptomics and molecular biology approaches to characterize reproductive-related genes in three sympatric Tomicus species. Illumina sequencing of female and male reproductive systems and residual bodies generated a large number of clean reads, representing 185,920,232 sequences in T. yunnanensis, 169,153,404 in T. brevipilosus and 178,493,176 in T. minor that were assembled into 32,802, 56,912 and 33,670 unigenes, respectively. The majority of the genes had detectable expression in reproductive tissues (FPKM >1), particularly those genes in T. brevipilosus accounting for 76.61 % of the total genes. From the transcriptomes, totally 838 genes encoding 463 detoxification enzymes, 339 chemosensory membrane proteins and 36 ionotropic glutamate receptors (iGluRs) were identified, including 622 reproductive tissue-expressed genes. Of these, members of carboxylesterases (COEs), ionotropic receptors (IRs), sensory neuron membrane proteins (SNMPs) and iGluRs were highly conserved in gene numbers and sequence identities across three Tomicus species. Further, expression profiling analyses revealed a number of genes expressed in reproductive tissues and the diverse expression characteristics in these beetles. The results provide evidence for the conservation and differences of reproductive genes among three sympatric closely related beetles, helping understand their different reproductive strategies and the maximization of the reproductive success.

Functional characterization of four antenna-biased chemosensory proteins in Dioryctria abietella reveals a broadly tuned olfactory DabiCSP1 and its key residues in ligand-binding.

The orientation of the oligophagous cone-feeding moth Dioryctria abietella (Lepidoptera: Pyralidae) to host plants primarily relies on olfactory-related proteins, particularly those candidates highly expressed in antennae. Here, through a combination of expression profile, ligand-binding assay, molecular docking and site-directed mutagenesis strategies, we characterized the chemosensory protein (CSP) gene family in D. abietella. Quantitative real-time PCR (qPCR) analyses revealed the detectable expression of all 22 DabiCSPs in the antennae, of which seven genes were significantly enriched in this tissue. In addition, the majority of the genes (19/22 relatives) had the expression in at least one reproductive tissue. In the interactions of four antenna-dominant DabiCSPs and different chemical classes, DabiCSP1 was broadly tuned to 27 plant-derived odors, three man-made insecticides and one herbicide with high affinities (Ki < 6.60 µM). By contrast, three other DabiCSPs (DabiCSP4, CSP6 and CSP17) exhibited a narrow odor binding spectrum, in response to six compounds for each protein. Our mutation analyses combined with molecular docking simulations and binding assays further identified four key residues (Tyr25, Thr26, Ile65 and Val69) in the interactions of DabiCSP1 and ligands, of which binding abilities of this protein to 12, 15, 16 and three compounds were significantly decreased compared to the wildtype protein, respectively. Our study reveals different odor binding spectra of four DabiCSPs enriched in antennae and identifies key residues responsible for the binding of DabiCSP1 and potentially active compounds for the control of this pest.

Diagnostic Significance of DCE-MRI-Related Quantitative Parameters for Nasal Cavity and Sinus Tumors.

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the clinical presentation and outcomes?

BACKGROUND: Whether clinical outcomes of acute cholangitis (AC) vary by etiology is unclear. AIM: To compare outcomes in AC caused by malignant biliary obstruction (MBO) and common bile duct stones (CBDS). METHODS: This retrospective study included 516 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) due to AC caused by MBO (MBO group, n = 56) and CBDS (CBDS group, n = 460). Clinical and laboratory parameters were compared between the groups. Propensity score matching (PSM) created 55 matched pairs. Confounders used in the PSM analysis were age, sex, time to ERCP, and technical success of ERCP. The primary outcome comparison was 30-d mortality. The secondary outcome comparisons were intensive care unit (ICU) admission rate, length of hospital stay (LOHS), and 30-d readmission rate. RESULTS: Compared with the CBDS group, the MBO group had significantly lower body temperature, percentage of abnormal white blood cell counts, and serum levels of aspartate aminotransferase, alanine aminotransferase, and creatinine. Body temperature, percent abnormal white blood cell count, and serum aspartate aminotransferase levels remained significantly lower in the MBO group in the PSM analysis. Platelet count, prothrombin time/international normalized ratio, and serum levels of alkaline phosphatase and total bilirubin were significantly higher in the MBO group. The MBO group had a significantly higher percentage of severe AC (33.9% vs 22.0%, P = 0.045) and received ERCP later (median, 92.5 h vs 47.4 h, P < 0.001). However, the two differences were not found in the PSM analysis. The 30-d mortality (5.4% vs 0.7%, P = 0.019), ICU admission rates (12.5% vs 4.8%, P = 0.028), 30-d readmission rates (23.2% vs 8.0%, P < 0.001), and LOHS (median, 16.5 d vs 7.0 d, P < 0.001) were significantly higher or longer in the MBO group. However, only LOHS remained significant in the PSM analysis. Multivariate analysis revealed that time to ERCP and multiple organ dysfunction were independent factors associated with 30-d mortality. CONCLUSION: MBO patients underwent ERCP later and thus had a worse prognosis than CBDS patients. Therefore, clinicians should remain vigilant in MBO patients with clinically suspected AC, and perform ERCP for biliary drainage as soon as possible.

The Impact of Metabolic Factors and Lipid-Lowering Drugs on Common Bile Duct Stone Recurrence after Endoscopic Sphincterotomy with Following Cholecystectomy.

BACKGROUND: Recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography is an undesirable problem, even when a following cholecystectomy is carried out. Important factors are the composition and properties of stones; the most significant etiology among these is the lipid level. While numerous studies have established the association between serum lipid levels and gallstones, no study has previously reported on recurrent common bile duct stones after endoscopic sphincterotomy with following cholecystectomy. MATERIALS AND METHODS: We retrospectively collected 2016 patients underwent endoscopic sphincterotomy from 1 January 2015 to 31 December 2017 in Linkou Chang Gung Memorial Hospital. Finally, 303 patients whose serum lipid levels had been checked following a cholecystectomy after ERCP were included for analysis. We evaluated if metabolic factors including body weight, BMI, HbA1C, serum lipid profile, and lipid-lowering drugs may impact the rate of common bile duct stone recurrence. Furthermore, we tried to find if there is any factor that may impact time to recurrence. RESULTS: A serum HDL level ≥ 40 (p = 0.000, OR = 0.207, 95% CI = 0.114-0.376) is a protective factor, and a total cholesterol level ≥ 200 (p = 0.004, OR = 4.558, 95% CI = 1.625-12.787) is a risk factor of recurrent common bile duct stones after endoscopic sphincterotomy with cholecystectomy. Lipid-lowering drugs, specifically statins, have been shown to reduce the risk of recurrence significantly (p = 0.003, OR = 0.297, 95% CI = 0.132-0.665). No factors were found to impact the time to recurrence in this study. CONCLUSIONS: The serum lipid level could influence the recurrence of common bile duct stones after endoscopic sphincterotomy followed by cholecystectomy, and it appears that statins can reduce the risk of recurrence.

Gaussian Boson Sampling with Pseudo-Photon-Number-Resolving Detectors and Quantum Computational Advantage.

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for the characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical spoofing mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ∼600 yr using exact methods, whereas our quantum computer, Jiǔzhang 3.0, takes only 1.27 µs to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier∼3.1×10^{10} yr.

Fresh Washed Microbiota Transplantation Alters Gut Microbiota Metabolites to Ameliorate Sleeping Disorder Symptom of Autistic Children.

Accumulating studies have raised concerns about gut dysbiosis associating autism spectrum disorder (ASD) and its related symptoms. However, the effect of gut microbiota modification on the Chinese ASD population and its underlying mechanism were still elusive. Herein, we enrolled 24 ASD children to perform the first course of fresh washed microbiota transplantation (WMT), 18 patients decided to participate the second course, 13 of which stayed to participate the third course, and there were 8 patients at the fourth course. Then we evaluated the effects of fresh WMT on these patients and their related symptoms. Our results found that the sleeping disorder symptom was positively interrelated to ASD, fresh WMT significantly alleviated ASD and its sleeping disorder and constipation symptoms. In addition, WMT stably and continuously downregulated Bacteroides/Flavonifractor/Parasutterella while upregulated Prevotella_9 to decrease toxic metabolic production and improve detoxification by regulating glycolysis/myo-inositol/D-glucuronide/D-glucarate degradation, L-1,2-propanediol degradation, fatty acid ß-oxidation. Thus, our results suggested that fresh WMT moderated gut microbiome to improve the behavioral and sleeping disorder symptoms of ASD via decrease toxic metabolic production and improve detoxification. Which thus provides a promising gut ecological strategy for ASD children and its related symptoms treatments.

Measurement-Device-Independent Quantum Key Distribution Based on Decoherence-Free Subspaces with Logical Bell State Analyzer.

Measurement-device-independent quantum key distribution (MDI-QKD) enables two legitimate users to generate shared information-theoretic secure keys with immunity to all detector side attacks. However, the original proposal using polarization encoding is sensitive to polarization rotations stemming from birefringence in fibers or misalignment. To overcome this problem, here we propose a robust QKD protocol without detector vulnerabilities based on decoherence-free subspaces using polarization-entangled photon pairs. A logical Bell state analyzer is designed specifically for such encoding. The protocol exploits common parametric down-conversion sources, for which we develop a MDI-decoy-state method, and requires neither complex measurements nor a shared reference frame. We have analyzed the practical security in detail and presented a numerical simulation under various parameter regimes, showing the feasibility of the logical Bell state analyzer along with the potential that double communication distance can be achieved without a shared reference frame.

Efficacy of Fully Covered Self-Expandable Metal Stents for Distal Biliary Obstruction Caused by Pancreatic Ductal Adenocarcinoma: Primary Metal Stent vs. Metal Stent following Plastic Stent.

Fully covered self-expandable metallic stents (FCSEMSs) are inserted in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) to resolve malignant distal bile duct obstructions. Some patients receive FCSEMSs during primary endoscopic retrograde cholangiopancreatography (ERCP), and others receive FCSEMSs during a later session, after the placement of a plastic stent. We aimed to evaluate the efficacy of FCSEMSs for primary use or following plastic stent placement. A total of 159 patients with pancreatic adenocarcinoma (m:f, 102:57) who had achieved clinical success underwent ERCP with the placement of FCSEMSs for palliation of obstructive jaundice. One-hundred and three patients had received FCSEMSs in a first ERCP, and 56 had received FCSEMSs after prior plastic stenting. Twenty-two patients in the primary metal stent group and 18 in the prior plastic stent group had recurrent biliary obstruction (RBO). The RBO rates and self-expandable metal stent patency duration did not differ between the two groups. An FCSEMS longer than 6 cm was identified as a risk factor for RBO in patients with PDAC. Thus, choosing an appropriate FCSEMS length is an important factor in preventing FCSEMS dysfunction in patients with PDAC with malignant distal bile-duct obstruction.