Intelligent robot-assisted fracture reduction system for the treatment of unstable pelvic fractures.

BACKGROUND: Precise and minimally invasive closed reduction is the premise of minimally invasive internal fixation. This paper aims to explore the safety and efficacy of a robot-assisted fracture reduction system (RAFR) in the treatment of pelvic fractures and to analyze its clinical advantages and existing problems. METHODS: The RAFR system intelligently designed the optimal reduction path and target position based on a preoperative three-dimensional(3D) CT scan of the patient. The reduction robotic arm automatically reduced the affected hemipelvis according to the pre-planned reduction path. RESULTS: The average residual displacement was the 6.65 ± 3.59 mm. According to Matta's criteria, there were 7 excellent, 10 good, and 3 fair, and the excellent and good rate was 85%. No postoperative complications occurred. CONCLUSION: In our study, the RAFR system could complete accurate and minimally invasive closed reduction for most patients with unstable pelvic fractures, which could achieve good fracture reduction quality and short-term efficacy.

TROP2 promotes PINK1-mediated mitophagy and apoptosis to accelerate the progression of senile chronic obstructive pulmonary disease by up-regulating DRP1 expression.

Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterised by irreversible airflow limitation. The elderly are a vulnerable population for developing COPD. With the growth of age, physiological degenerative changes occur in the thorax, bronchus, lung and vascular wall, which can lead to age-related physiological attenuation of lung function in the elderly, so the prevalence of COPD increases with age. Its pathogenesis has not yet been truly clarified. Mitophagy plays an important role in maintaining the stability of mitochondrial function and intracellular environment by scavenging damaged mitochondria. Currently, studies have shown that trophoblast antigen 2 (TROP2) expression is up-regulated in airway basal cells of patients with COPD, suggesting that TROP2 is involved in the progression of COPD. However, whether it is involved in disease progression by regulating mitochondrial function remains unclear. In this study, compared with non-smoking non-COPD patients, the expression of TROP2 in lung tissues of smoking non-COPD patients and patients with COPD increased, and TROP2 expression in patients with COPD was higher than that in smoking non-COPD patients. To further explore the role of TROP2, we stimulated BEAS-2B with cigarette smoke to construct an in vitro model. We found that TROP2 expression increased, whereas TROP2 silencing reversed the cigarette smoke extract-induced decrease in mitochondrial membrane potential, increased reactive oxygen species content, decreased adenosine triphosphate (ATP) production, increased inflammatory factor secretion and increased apoptosis. In addition, we searched online bioinformatics and screened the gene dynamin-related protein 1 (DRP1) related to mitophagy as the research object. Co-IP assay verified the binding relationship between DRP1 and TROP2. Further study found that TROP2 promoted mitophagy and apoptosis of BEAS-2B cells by up-regulating the expression of DRP1. In addition, PTEN-induced putative kinase 1 (PINK1) is a potential binding protein of DRP1, and DRP1 accelerated mitophagy and apoptosis of BEAS-2B cells by promoting the expression of PINK1. We established a COPD SD rat model by cigarette smoke exposure and LPS instillation and treated it by intraperitoneal injection of si-TROP2. The results showed that TROP2 silencing restored lung function and reduced the secretion of inflammatory factors in bronchoalveolar lavage fluid. In conclusion, TROP2 can be used as a new reference for COPD treatment.

Demographics and prognosis of patients with pyogenic liver abscess due to Klebsiella pneumonia or other species.

Background: Pyogenic liver abscess (PLA) is a potentially life-threatening intra-abdominal infection. We compared the clinical features, treatments, and prognoses of patients who had Klebsiella pneumonia pyogenic liver abscess (KPPLA) and non-Klebsiella pneumonia pyogenic liver abscess (non-KPPLA). Methods: A retrospective analysis was used to compare the medical records of KPPLA and non-KPPLA patients with positive pus cultures at a single hospital in China from January 2017 to December 2019. Results: We examined 279 patients with definitively established PLA, 207 (74.2 %) with KPPLA, and 72 with non-KPPLA. The non-KPPLA group had a higher Charlson comorbidity index, longer hospital stay, longer duration of fever, and greater hospital costs. Multivariate analysis showed that alcohol intake (OR: 2.44, P = 0.048), cancer (OR: 4.80, P = 0.001), ICU admission (OR: 10.61, P = 0.026), resolution of fever OR: 1.04, P = 0.020), and a positive blood culture (OR: 2.87, P = 0.029) were independent predictors of primary treatment failure. Percutaneous needle aspiration (PNA) and pigtail catheter drainage (PCD) provided satisfactory outcomes, but PNA led to shorter hospital stays and reduced costs, especially in KPPLA patients whose abscesses were smaller than 10 cm. Conclusion: KPPLA and non-KPPLA patients had some differences in comorbidities and treatment strategies, and non-KPPLA patients had a significantly worse prognosis.

Correlation between blood glucose level and poor wound healing after posterior lumbar interbody fusion in patients with type 2 diabetes.

To investigate the correlation of blood glucose level with poor wound healing (PWH) after posterior lumbar interbody fusion (PLIF) in patients with type 2 diabetes (T2D). From January 2016 to January 2023, a case-control study was conducted to analyse the clinical data of 400 patients with T2D who were treated by PLIF and internal fixation at our hospital. The following data were recorded: gender; age; body mass index (BMI); surgical stage; average perioperative blood glucose level; perioperative blood glucose variance; perioperative blood glucose coefficient of variation; glycated haemoglobin level; preoperative levels of total protein, albumin and haemoglobin; postoperative levels of total protein, albumin and haemoglobin; surgical time; intraoperative bleeding volume; operator; postoperative drainage volume; and postoperative drainage tube removal time of each group. The indicators for monitoring blood glucose variability (GV) included the SD of blood glucose level (SDBG), coefficient of variation (CV) and maximum amplitude of variation (LAGE) before and after surgery. According to the diagnostic criteria for PWH, patients with postoperative PWH were determined and assigned to two groups: Group A (good wound healing group; n = 330 patients) and Group B (poor wound healing group; n = 70 patients). The preoperative and postoperative blood GV indicators, namely SDBG, CV and LAGE, were compared between these two groups. We also determined the relationship between perioperative blood GV parameters and PWH after PLIF surgery and its predictive value through correlation analysis and receiver-operating characteristic curve. Of the 400 enrolled patients, 70 patients had PWH. Univariate analysis revealed significant differences between the two groups in the course of diabetes, mean fasting blood glucose (MFBG), SDBG, CV, LAGE, preoperative hypoglycaemic program, surgical segment, postoperative drainage time, incision length and other factors (p < 0.05). However, no significant differences were noted in factors such as gender, age, body mass index, hypertension, coronary heart disease, admission fasting blood glucose, preoperative haemoglobin A1c, surgical time, intraoperative bleeding volume, intraoperative blood transfusion volume and postoperative drainage volume (p > 0.05). The area under the curve (AUC) values of preoperative SDBG, CV and LAGE were 0.6657, 0.6432 and 0.6584, respectively. The cut-off values were 1.13 mmol/L, 6.97% and 0.75 mmol/L, respectively. The AUC values for postoperative SDBG, CV and LAGE were 0.5885, 0.6255 and 0.6261, respectively. The cut-off values were 1.94 mmol/L, 24.32% and 2.75 mmol/L, respectively. The multivariate ridge regression analysis showed that preoperative MFBG, SDBG, CV and LAGE; postoperative SDBG, CV and LAGE; postoperative long drainage time; and multiple surgical segments were independent risk factors for T2D patients to develop surgical site infection after PLIF (p < 0.05). The perioperative blood GV in patients with T2D is closely related to the occurrence of PWH after PLIF. Reducing blood GV may help to reduce the occurrence of PWH after PLIF.

Akkermansia muciniphila attenuated lipopolysaccharide-induced acute lung injury by modulating the gut microbiota and SCFAs in mice.

Gut microbiota are closely related to lipopolysaccharide (LPS)-induced acute lung injury (ALI). Akkermansia muciniphila (A. muciniphila) maintains the intestinal barrier function and regulates the balance of reduced glutathione/oxidized glutathione. However, it may be useful as a treatment strategy for LPS-induced lung injury. Our study aimed to explore whether A. muciniphila could improve lung injury by affecting the gut microbiota. The administration of A. muciniphila effectively attenuated lung injury tissue damage and significantly decreased the oxidative stress and inflammatory reaction induced by LPS, with lower levels of myeloperoxidase (MDA), enhanced superoxide dismutase (SOD) activity, decreased pro-inflammatory cytokine levels, and reduced macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained the intestinal barrier function, reshaped the disordered microbial community, and promoted the secretion of short-chain fatty acids (SCFAs). A. muciniphila significantly downregulated the expression of TLR2, MyD88 and NF-kappa B (P < 0.05). Butyrate supplementation demonstrated a significant improvement in the inflammatory response (P < 0.05) and mitigation of histopathological damage in mice with ALI, thereby restoring the intestinal butyric acid concentration. In conclusion, our findings indicate that A. muciniphila inhibits the accumulation of inflammatory cytokines and attenuates the activation of the TLR2/Myd88/NF-κB pathway due to exerting anti-inflammatory effects through butyrate. This study provides an experimental foundation for the potential application of A. muciniphila and butyrate in the prevention and treatment of ALI.

Lactobacillus reuteri Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Modulating the Gut Microbiota in Mice.

Acute lung injury (ALI) causes lung inflammation and edema as well as resulting in gut microbiota disorder. Probiotics, however, can improve the gut microbiota composition and modulate its immune response, playing an important role in ALI pathogenesis. Therefore, our study aims to investigate the effect of Lactobacillus reuteri on Lipopolysaccharide (LPS)-induced ALI in mice and to probe the mechanism of its synergistic modulatory effect on the lungs and intestines. We assessed the therapeutic effects of L. reuteri in the ALI mouse model by histopathology, alveolar lavage fluid and serum inflammatory factor analysis and explored microbiome and transcriptome alterations. L. reuteri intervention effectively attenuated lung tissue injury and significantly reduced the LPS-induced inflammatory response and macrophage and neutrophil infiltration. Additionally, L. reuteri improved the intestinal barrier function and remodeled the disordered microbiota. In conclusion, our study showed that L. reuteri attenuated the inflammatory response, ameliorated the pulmonary edema, repaired the intestinal barrier, and remodeled the gut microbiota in ALI mice. This study provides new perspectives on the clinical treatment of ALI.

Endoscopic optical coherence tomography angiography using an externally driving catheter.

Endoscopic optical coherence tomography (OCT) is an imaging modality that enables cross-sectional subsurface imaging of tubular organs and cavities. Recently, endoscopic OCT angiography (OCTA) was successfully achieved in distal scanning systems using an internal-motor-driving catheter. In conventional OCT systems using externally driving catheters, the mechanical instability in the proximal actuation causes difficulties for differentiating capillaries in tissues. In this study, OCTA in an endoscopic OCT system using an external-motor-driving catheter was proposed. Blood vessels were visualized by using a high-stability inter-A-scan scheme and the spatiotemporal singular value decomposition algorithm. It is not limited by nonuniform rotation distortion caused by the catheter and physiological motion artifacts. Results show that microvasculature in a custom-made microfluidic phantom and the submucosal capillaries in the mouse rectum are successfully visualized. Furthermore, OCTA using a catheter with a small size (outer diameter less than 1 mm) makes it possible for early diagnosis of narrow lumens, such as pancreatic and bile duct cancers.

The impact of dietary fibers on Clostridioides difficile infection in a mouse model.

Diets rich in fiber may provide health benefits and regulate the gut microbiome, which affects the immune system. However, the role of dietary fiber in Clostridioides difficile infection (CDI) is controversial. Here, we investigated the use of fermentable fibers, such as inulin or pectin, to replace the insoluble fiber cellulose to explore how dietary fiber affects C. difficile-induced colitis in mice through intestinal microecology and metabolomics. Using C. difficile VPI 10463, we generated a mouse model of antibiotic-induced CDI. We evaluated disease outcomes and the microbial community among mice fed two fermentable fibers (inulin or pectin) versus the insoluble fiber cellulose. We analyzed and compared the gut microbiota, intestinal epithelium, cytokine levels, immune responses, and metabolites between the groups. Severe histological injury and elevated cytokine levels were observed in colon tissues after infection. Different diets showed different effects, and pectin administration protected intestinal epithelial permeability. Pectin also steadily increased the diversity of the microbiome and decreased the levels of C. difficile-induced markers of inflammation in serum and colonic tissues. The pectin group showed a higher abundance of Lachnospiraceae and a lower abundance of the conditionally pathogenic Enterobacteriaceae than the cellulose group with infection. The concentration of short-chain fatty acids in the cecal contents was also higher in the pectin group than in the cellulose group. Pectin exerted its effects through the aryl hydrocarbon receptor (AhR) pathway, which was confirmed by using the AhR agonist FICZ and the inhibitor CH2223191. Our results show that pectin alters the microbiome and metabolic function and triggers a protective immune response.

Apple Polyphenol Extract Suppresses Clostridioides difficile Infection in a Mouse Model.

Fruits such as apples are a dietary source of polyphenols and have health benefits. We studied the benefits of apple polyphenols in reducing intestinal infections. We explored the potential roles of apple polyphenols in combating Clostridioides difficile-induced intestinal infections by modulating the intestinal microbiota and metabolism in our study. Mice fed with apple polyphenols exhibited higher survival rates and improved diarrhea symptoms in a C. difficile infection mouse model given once-daily apple polyphenol extract (200 or 400 mg/kg bw) or phosphate-buffered saline. Feeding polyphenols enhanced anti-inflammatory effects and colon barrier integrity. In addition, apple polyphenols mitigated intestinal microbiota disorders in C. difficile infection, modulating the intestinal microbiota and increasing the abundance of beneficial microbiota. Apple polyphenols also improved fecal metabolic alterations in C. difficile-infected mice and modulated the expression of pathways related to intestinal inflammation. Our results suggest that apple polyphenol extract is a potential prebiotic agent that affects the intestinal microbiota and metabolism, thereby positively influencing intestinal infections.

The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.

Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1ß, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.

Epigallocatechin-3-Gallate Improves Intestinal Gut Microbiota Homeostasis and Ameliorates Clostridioides difficile Infection.

Clostridioides difficile infection is closely related to the intestinal flora disorders induced by antibiotics, and changes in the intestinal flora may cause the occurrence and development of Clostridioides difficile infection. Epigallocatechin-3-gallate (EGCG) is one of the major bioactive ingredients of green tea and has been suggested to alleviate the growth of C. difficile in vitro. EGCG can ameliorate several diseases, such as obesity, by regulating the gut microbiota. However, whether EGCG can attenuate C. difficile infection by improving the gut microbiota is unknown. After establishing a mouse model of C. difficile infection, mice were administered EGCG (25 or 50 mg/kg/day) or PBS intragastrically for 2 weeks to assess the benefits of EGCG. Colonic pathology, inflammation, the intestinal barrier, gut microbiota composition, metabolomics, and the transcriptome were evaluated in the different groups. Compared with those of the mice in the CDI group, EGCG improved survival rates after infection, improved inflammatory markers, and restored the damage to the intestinal barrier. Furthermore, EGCG could improve the intestinal microbial community caused by C. difficile infection, such as by reducing the relative abundance of Enterococcaceae and Enterobacteriaceae. Moreover, EGCG can increase short-chain fatty acids, improve amino acid metabolism, and downregulate pathways related to intestinal inflammation. EGCG alters the microbiota and alleviates C. difficile infection, which provides new insights into potential therapies.

Multi-Omics Analysis Reveals the Protection of Gasdermin D in Concanavalin A-Induced Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a progressive inflammation-associated liver injury. Pyroptosis is a novel inflammatory programmed cell death wherein gasdermin D (GSDMD) serves as the executioner. Our work challenged Gsdmd-/- mice with concanavalin A (ConA) to try to unveil the actual role of GSDMD in AIH. After ConA injection, Gsdmd-/- mice exhibited more severe liver damage characterized by a lower survival rate, more extensive hepatocyte necrosis and apoptosis, and higher serum transaminase levels, indicating the protection of GSDMD in ConA-induced AIH. Furthermore, the Gsdmd-/- mice exhibited higher hepatic expression and serum levels of inflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-17A [IL-17A]) and more infiltration of macrophages and neutrophils after ConA treatment than did wild-type (WT) mice. Gsdmd-/- mice with AIH showed increased hepatic l-glutamine levels but decreased glycerophospholipid metabolites levels. L-glutamine levels showed positive correlations while glycerophospholipid metabolites showed negative associations with liver injury indexes and inflammation markers. We further observed a destroyed intestinal barrier in Gsdmd-/- mice after ConA injection as indicated by decreased transcriptional expressions of Tjp1, Ocln, Reg3g, and Muc2. ConA-treated Gsdmd-/- mice also exhibited higher serum LPS binding protein (LBP) concentrations and hepatic Tlr4 and Cd14 mRNA levels. Further fecal 16S rRNA gene sequencing demonstrated decreased relative abundances of Lactobacillus and Roseburia but increased relative abundances of Allobaculum and Dubosiella in Gsdmd-/- mice with AIH. Lactobacillus was negatively correlated with liver injury and inflammation indexes and positively associated with Ocln, Muc2, and Reg3g levels. Allobaculum was positively related to liver injury and inflammatory cytokines and negatively correlated with gut barrier indexes. IMPORTANCE Our study provides the first direct clues to the protective role of gasdermin D (GSDMD) in autoimmune hepatitis (AIH). We demonstrated that Gsdmd knockout exacerbated concanavalin A (ConA)-induced AIH in mice. It may be due to the destroyed intestinal barrier and changes in certain intestinal microbes and hepatic metabolites resulting in increased liver injury and inflammation in ConA-treated Gsdmd-/- mice. This finding suggested a nonnegligible role of GSDMD in AIH and also confirmed its physiological nonpyroptosis effects on the host. The role of GSDMD in autoimmune liver diseases or other liver diseases is complex and intriguing, deserving deep investigation.

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites.

Clostridioides difficile is a common cause of nosocomial infection. Antibiotic-induced dysbiosis in the intestinal microbiota is a core cause of C. difficile infection (CDI). Akkermansia muciniphila plays an active role in maintaining gastrointestinal balance and might offer the protective effects on CDI as probiotics. Here, we investigated the effects and mechanisms of A. muciniphila on CDI. C57BL/6 mice (n = 29) were administered A. muciniphila Muc T (3 × 109 CFUs, 0.2 mL) or phosphate-buffered saline (PBS) by oral gavage for 2 weeks. Mice were pretreated with an antibiotic cocktail and subsequently challenged with the C. difficile strain VPI 10463. A. muciniphila treatment prevented weight loss in mice and reduced the histological injury of the colon. And it also alleviated inflammation and improved the barrier function of the intestine. The administration effects of A. muciniphila may be associated with an increase in short-chain fatty acid production and the maintenance of bile acids' steady-state. Our results provide evidence that administration of A. muciniphila to CDI mice, with an imbalance in the microbial community structure, lead to a decrease in abundance of members of the Enterobacteriaceae and Enterococcaceae. In short, A. muciniphila shows a potential anti-CDI role by modulating gut microbiota and the metabolome.

Modulation of Lactobacillus rhamnosus GG on the gut microbiota and metabolism in mice with Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is a common nosocomial infection and is an urgent threat to public health. Vancomycin is the preferred antibiotic treatment for CDI but is associated with recurrence. Lactobacillus rhamnosus GG is an adjunctive treatment for gastroenteritis and diarrhea and exerts its effects by modulating the immune responses and repairing the intestinal barrier. This study explored the effect of LGG on restoring the intestinal microbiota in mouse models. Primary and recurrent CDI models were constructed, and LGG was administered to C57BL/6 mice. Structural changes in the mouse gut microbiota were determined using 16S rRNA gene analysis based on Illumina sequencing. In the CDI model, 6 days after infection, 33.3% mortality, significant weight loss and colonic injury were observed. LGG can ameliorate these events. In the R-CDI mouse model, vancomycin combined with LGG prevented weight loss, improved the histopathological scores, and effectively reduced the mortality. LGG + vancomycin administration promoted the recovery of the intestinal flora by inhibiting Enterococcus and counteracting the side effects of vancomycin treatment. In both the preventive and therapeutic CDI mouse models, the oral LGG strain showed the ability to protect against primary and recurrent infections, indicating that probiotics have potential for treating intestinal diseases. Overall, these observations suggest that LGG can be applied as a preventive treatment for CDI or in combination with antibiotics to reduce recurrence.

Identification of a protective Bacteroides strain of alcoholic liver disease and its synergistic effect with pectin.

The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: • B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. • The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. • The synbiotic combination modulates gut microbiota and tryptophan metabolism.

Integrated US-OCT-NIRF Tri-Modality Endoscopic Imaging System for Pancreaticobiliary Duct Imaging.

Pancreaticobiliary carcinomas is a highly malignant gastrointestinal tumor. Most pancreaticobiliary cancers arise from epithelial proliferation within the pancreaticobiliary ducts, referred to as pancreatic intraepithelial neoplasias (PanINs). Some PanINs are benign metaplasia, while others progress to invasive duct adenocarcinoma (IDAC). However, there is no standard program to diagnose the progression from PanINs to IDAC. In this study, we present a tri-modality imaging system, which integrates ultrasound (US), optical coherence tomography (OCT), and near-infrared fluorescence (NIRF) for pancreaticobiliary duct imaging. This system can obtain OCT, US, and NIRF images in real-time with a frame rate of 30 frames per second. For the endoscopy probe with an outer diameter of 0.9 mm, the US transducer and fiber ball lens were placed back to back. In vivo experiments were performed on the rectums of Sprague-Dawley rats to demonstrate the imaging performance of US, OCT, and fluorescence angiography. An ex vivo experiment on a human pancreatic duct was performed for a more accurate assessment of the pancreaticobiliary duct. The tomography images of rat rectums and human pancreatic ducts were correlated with hematoxylin and eosin (H&E) histology to check the measurement accuracy. The integrated tri-modality system has great clinical potential in mechanism studies, early diagnosis, and prognosis evaluation of malignant pancreaticobiliary carcinomas.

Transcranial Focused Ultrasound Stimulation of Periaqueductal Gray for Analgesia.

OBJECTIVE: Transcranial focused ultrasound (tFUS) is regarded as a promising non-invasive stimulation tool for modulating brain circuits. The aim of this study is to explore the feasibility of tFUS stimulation for analgesia applications. METHODS: 50 µl of 3% formalin solution was injected into the rat's left hindpaw to build a pain model, and then the local field potential (LFP) activities of the dorsal horn were tracked after a recording electrode was placed in the spinal cord. Rats were randomly divided into two groups: control group and tFUS group. At the 30th minute after formalin injection, tFUS (US-650 kHz, PD = 1 ms, PRF = 100 Hz, 691 mW/cm2) was conducted to stimulate the periaqueductal gray (PAG) for 5 minutes (on 5 s and off 5 s) in the tFUS group, but there was no treatment in the control group. In addition, the analgesia mechanism (LFP recording from the PAG) and safety assessment (histology analysis) were carried out. RESULTS: The tFUS stimulation of the PAG can suppress effectively the nociceptive activity generated by formalin. The findings of the underlying mechanism exploration indicated that the tFUS stimulation was able to activate the PAG directly without causing notable temperature change and tissue injury. CONCLUSION: The results illustrated that the tFUS stimulation of the PAG can achieve the effect of analgesia. SIGNIFICANCE: This work provides new insights into the development of non-invasive analgesic technology in the future.

Akkermansia muciniphila Ameliorates Acetaminophen-Induced Liver Injury by Regulating Gut Microbial Composition and Metabolism.

The gut microbiota drives individual sensitivity to excess acetaminophen (APAP)-mediated hepatotoxicity. It has been reported that the bacterium Akkermansia muciniphila protects hosts against liver disease via the liver-gut axis, but its therapeutic potential for drug-induced liver injury remains unclear. In this study, we aimed to investigate the effect of A. muciniphila on APAP-induced liver injury and the underlying mechanism. Administration of A. muciniphila efficiently alleviated APAP-induced hepatotoxicity and reduced the levels of serum alanine aminotransferase (ALT) and aspartate transaminase (AST). A. muciniphila significantly attenuated APAP-induced oxidative stress and the inflammatory response, as evidenced by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, enhanced superoxide dismutase (SOD) activity, reduced proinflammatory cytokine production, and alleviation of macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained gut barrier function, reshaped the perturbed microbial community and promoted short-chain fatty acid (SCFA) secretion. The beneficial effects of A. muciniphila were accompanied by alterations in hepatic gene expression at the transcriptional level and activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results suggested that A. muciniphila could be a potential pretreatment for APAP-induced liver injury. IMPORTANCE Our work revealed that A. muciniphila attenuated APAP-induced liver injury by alleviating oxidative stress and inflammation in the liver, and its hepatoprotective effect was accompanied by activation of the PI3K/Akt pathway and mediated by regulation of the composition and metabolic function of the intestinal microbiota. This finding suggested that the microbial community is a non-negligible impact on drug metabolism and probiotic administration could be a potential therapy for drug-induced liver injury.

A comparison of demographic, epidemiological and clinical characteristics of hospital influenza-related viral pneumonia patients.

BACKGROUND: Through the comparison of the demographic, epidemiological, and clinical characteristics of hospital human influenza (influenza A (H1N1) pdm09, H3N2, and B)-related and hospitalized avian-origin influenza A (H7N9)-related viral pneumonia patients, find the different between them. METHODS: A retrospective study was conducted in hospitalized influenza-related viral pneumonia patients. RESULTS: Human influenza A-related patients in the 35-49-year-old group were more than those with B pneumonia patients (p = 0.027), and relatively less in the ≥ 65-year-old group than B pneumonia patients (p = 0.079). The proportion of comorbid condition to human influenza A pneumonia was 58%, lower than B pneumonia and H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). The proportion of invasive mechanical ventilation (IMV), lymphocytopenia, elevated lactate dehydrogenase to hospitalized human influenza A-related viral pneumonia patients was higher than B pneumonia patients (p < 0.05), but lower than H7N9 pneumonia patients (p < 0.05). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI) 1.54-121.12; p = 0.019) and positive bacterial culture (sputum) (OR: 7.71; 95% CI 2.48-24.03; p < 0.001) were independently associated with IMV, while shock (OR: 13.16; 95% CI 2.06-84.07; p = 0.006), white blood cell count > 10,000/mm3 (OR: 7.22; 95% CI 1.47-35.58; p = 0.015) and positive bacterial culture(blood or sputum) (OR: 6.27; 95% CI 1.36-28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients. CONCLUSIONS: Hospital influenza B-related viral pneumonia mainly affects the elderly and people with underlying diseases, while human influenza A pneumonia mainly affects the young adults; however, the mortality was similar. The hospitalized human influenza A-related viral pneumonia patients was severer than B pneumonia patients, but milder than H7N9 pneumonia patients. Pulmonary consolidation and positive bacterial culture (sputum) were independently associated with IMV, while shock, white blood cell count > 10,000/mm3, and positive bacterial culture (blood or sputum) were independently associated with death to three types hospitalized influenza-related viral pneumonia patients.

Hematological and cytochemical characteristics of peripheral blood cells in the argus snakehead (Ophiocephalus argus Cantor).

BACKGROUND: The argus snakehead (Ophiocephalus argus Cantor) is a highly nutritious, freshwater, cultured bony fish with a high economic value. The health of the fish is closely related to its blood cells, which are critical for oxygen transport, natural defense, and immunity. We investigated the morphometry, microstructure, and cytochemical characteristics of the peripheral blood cells of O. argus. Our results may provide the basic reference values needed to monitor the health of this fish for large-scale cultivation. METHODS: The number of blood cells in O. argus were counted on a hemocytometer and their size was measured using a micrometer under light microscope. The morphology and classification of the blood cells were studied using Wright's staining and the cytochemical characteristics were studied using seven chemical stains including peroxidase (POX), Sudan black B (SBB), periodic acid-Schiff (PAS), acid phosphatase (ACP), alkaline phosphatase (ALP), chloroacetic acid AS-D naphthol esterase (AS-D), and α-naphthol acetate esterase (α-NAE). RESULTS: The peripheral blood cells in O. argus can be classified as erythrocytes, leukocytes, and thrombocytes; of which, females had 2.9597 million/mm3, 88,400/mm3, and 43,600/mm3, respectively, and males had 3.0105 million/mm3, 105,500/mm3, and 34,000/mm3, respectively. Leukocytes consisted of neutrophils, monocytes, large lymphocytes, and small lymphocytes. Eosinophils and basophils were not found. Monocytes were the most numerous leukocytes identified, followed by neutrophils and small lymphocytes, while large lymphocytes were the least frequently identified. Cytochemical staining showed that erythrocytes were only positive for PAS staining. Neutrophils were strongly positive for POX, SBB, and ACP, and positive for all the other cytochemical stains. Monocytes were positive for PAS and α-NAE and were weakly positive for ACP and AS-D staining. Large lymphocytes were positive for PAS and were weakly positive for ALP, AS-D, and α-NAE staining. Small lymphocytes were positive for PAS and weakly positive for AS-D and α-NAE staining. Thrombocytes were positive for PAS and were weakly positive for ACP and AS-D, but negative for the remaining cytochemical stains. The morphology of peripheral blood cells in O. argus was generally similar to that of other fish species, while the cytochemical staining patterns showed clear species specificity.