[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

Comparative effectiveness of angioembolization versus open surgery in patients with blunt splenic injury.

The effectiveness and safety of transcatheter splenic artery embolization (SAE) compared to those of open surgery in patients with blunt splenic injury (BSI) remain unclear. This retrospective cohort-matched study utilized data from the Japan Trauma Data Bank recorded between 2004 and 2019. Patients with BSI who underwent SAE or open surgery were selected. A propensity score matching analysis was used to balance the baseline covariates and compare outcomes, including all-cause in-hospital mortality and spleen salvage. From 361,706 patients recorded in the data source, this study included 2,192 patients with BSI who underwent SAE or open surgery. A propensity score matching analysis was used to extract 377 matched pairs of patients. The in-hospital mortality rates (SAE, 11.6% vs. open surgery, 11.2%, adjusted relative risk (aRR): 0.64; 95% confidence interval [CI]: 0.38-1.09, p = 0.10) were similar in both the groups. However, spleen salvage was significantly less achieved in the open surgery group than in the SAE group (SAE, 87.1% vs. open surgery, 32.1%; aRR: 2.84, 95%CI: 2.29-3.51, p < 0.001). Survival rates did not significantly differ between BSI patients undergoing SAE and those undergoing open surgery. Nonetheless, SAE was notably associated with a higher likelihood of successful spleen salvage.

High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen.

High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

Correlation between spleen density and prognostic outcomes in patients with colorectal cancer after curative resection.

OBJECTIVE: The objective of this study was to investigate the correlation between spleen density and the prognostic outcomes of patients who underwent curative resection for colorectal cancer (CRC). METHODS: The clinical data of patients who were diagnosed with CRC and underwent radical resection were retrospectively analyzed. Spleen density was determined using computed tomography. Analysis of spleen density in relation to overall survival (OS) and disease-free survival (DFS) utilizing the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict OS and DFS. Moreover, internally validated using a bootstrap resamplling method. RESULTS: Two hundred twelve patients were included, of whom 23 (10.85%) were defined as having a diffuse reduction of spleen density (DROSD) based on diagnostic cutoff values (spleen density≦37.00HU). Kaplan-Meier analysis indicated that patients with DROSD had worse OS and DFS than those non-DROSD (P < 0.05). Multivariate Cox regression analysis revealed that DROSD, carbohydrate antigen 199 (CA199) > 37 U/mL, tumor node metastasis (TNM) stage III-IV, laparoscopy-assisted operation and American Society of Anesthesiology (ASA) score were independent risk factors for 3-year DFS. DROSD, CA199 > 37 U/mL, TNM stage III-IV, hypoalbuminemia, laparoscopy-assisted operation and ASA score were chosen as predictors of for 3-year OS. Nomograms showed satisfactory accuracy in predicting OS and DFS using calibration curves, decision curve analysis and bootstrap resamplling method. CONCLUSION: Patients with DROSD who underwent curative resection have worse 3-year DFS and OS. The nomogram demonstrated good performance, particularly in predicting 3-year DFS with a net clinical benefit superior to well-established risk calculator.

A new method to predict venous complications in pediatric liver transplantation: Evaluation of splenic parameters by ultrasonography.

BACKGROUND: Venous complications after pediatric liver transplantation seriously affect the survival rate of patients and grafts. At present, the diagnostic indicators have not been unified. Venous complications may cause portal hypertension, which may lead to splenomegaly and splenic vein dilatation. Therefore, the changes in spleen may be closely related to the venous complications. The purpose of this study was to explore the relationship between ultrasonic splenic parameters and venous complications and to study whether these splenic parameters can be used for the diagnosis of venous complications. METHODS: We retrospectively included pediatric patients who underwent liver transplantation and collected ultrasonic spleen parameters before, and then 1-3 days, 1-3 weeks, 1-3 months, and 4-12 months after liver transplantation. We observed whether there were portal vein or hepatic vein complications within 1 year after liver transplantation. RESULTS: Among 109 pediatric patients after liver transplantation included in our study, 11 of them suffered from portal vein complications and nine hepatic vein complications. Spleen transverse diameter, spleen longitudinal diameter, spleen portal vein diameter, spleen index, spleen transverse diameter ratio, spleen longitudinal diameter ratio, and spleen index ratio were independent risk factors of venous complications. The accuracy of spleen transverse diameter (AUROC: 0.73), spleen index (AUROC: 0.70), spleen transverse diameter ratio (AUROC: 0.71), and spleen index ratio (AUROC: 0.72) in predicting venous complications were higher than other ones. CONCLUSIONS: Ultrasonic examination is a common follow-up method for pediatric patients after liver transplantation and the application of ultrasonic spleen parameters may be helpful to monitor venous complications.

Relation between resting spleen volume and apnea-induced increases in hemoglobin mass.

Introduction: Indigenous populations renowned for apneic diving have comparatively large spleen volumes. It has been proposed that a larger spleen translates to heightened apnea-induced splenic contraction and elevations in circulating hemoglobin mass (Hbmass), which, in theory, improves O2 carrying and/or CO2/pH buffering capacities. However, the relation between resting spleen volume and apnea- induced increases in Hbmass is unknown. Therefore, we tested the hypothesis that resting spleen volume is positively related to apnea-induced increases in total Hbmass. Methods: Fourteen healthy adults (six women; 29 ± 5 years) completed a two-minute carbon monoxide rebreathe procedure to measure pre-apneas Hbmass and blood volume. Spleen length, width, and thickness were measured pre-and post-five maximal apneas via ultrasound. Spleen volume was calculated via the Pilström equation (test-retest CV:2 ± 2%). Hemoglobin concentration ([Hb]; g/dl) and hematocrit (%) were measured pre- and post-apneas via capillary blood samples. Post-apneas Hbmass was estimated as post-apnea [Hb] x pre-apnea blood volume. Data are presented as mean ± SD. Results: Spleen volume decreased from pre- (247 ± 95 mL) to post- (200 ± 82 mL, p<0.01) apneas. [Hb] (14.6 ± 1.2 vs. 14.9 ± 1.2 g/dL, p<0.01), hematocrit (44 ± 3 vs. 45 ± 3%, p=0.04), and Hbmass (1025 ± 322 vs. 1046 ± 339 g, p=0.03) increased from pre- to post-apneas. Pre-apneas spleen volume was unrelated to post-apneas increases in Hbmass (r=-0.02, p=0.47). O2 (+28 ± 31 mL, p<0.01) and CO2 (+31 ± 35 mL, p<0.01) carrying capacities increased post-apneas. Conclusion: Larger spleen volume is not associated with a greater rise in apneas-induced increases in Hbmass in non-apnea-trained healthy adults.

Blood defense system - Proposal for a new concept of an immune system against blood borne pathogens comprising the liver, spleen and bone marrow.

Blood-borne pathogen (BBP) infections can rapidly progress to life-threatening sepsis and must therefore be promptly eliminated by the host's immune system. Intravascular macrophages of the liver sinusoid, splenic marginal zone and red pulp and perisinusoidal macrophage protrusions in the bone marrow (BM) directly phagocytose BBPs in the blood as an innate immune response. The liver, spleen and BM thereby work together as the blood defence system (BDS) in response to BBPs by exerting their different immunological roles. The liver removes the vast majority of these invading organisms via innate immunity, but their complete elimination is not possible without the actions of antibodies. Splenic marginal zone B cells promptly produce IgM and IgG antibodies against BBPs. The splenic marginal zone transports antigenic information from the innate to the adaptive immune systems. The white pulp of the spleen functions as adaptive immune tissue and produces specific and high-affinity antibodies with an immune memory against BBPs. The BM works to maintain immune memory by supporting the survival of memory B cells, memory T cells and long-lived plasma cells (LLPCs), all of which have dedicated niches. Furthermore, BM perisinusoidal naïve follicular B cells promptly produce IgM antibodies against BBPs in the BM sinusoid and the IgG memory B cells residing in the BM rapidly transform to plasma cells which produce high-affinity IgG antibodies upon reinfection. This review describes the complete immune defence characteristics of the BDS against BBPs through the collaboration of the liver, spleen and BM with combined different immunological roles.

Transmissibility of Mycobacterium pinnipedii in a murine model.

The causative agent of tuberculosis in pinnipeds is Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex (MTC). The natural hosts are pinnipeds; however, other non-marine mammals, including humans, can also be infected. The transmissibility of a pathogen is related to its virulence. The transmissibility of a M. pinnipedii strain (i.e., 1856) was investigated in a murine model and compared with that of two Mycobacterium bovis strains (i.e., 534 and 04-303) with different reported virulence. Non-inoculated mice (sentinels) were co-housed with intratracheally inoculated mice. Detailed inspection of mice to search for visible tuberculosis lesions in the lungs and spleen was performed, and bacillus viability at 30, 60, and 90 days post-inoculation (dpi) was assayed. A transmissibility of 100% was recorded at 30 dpi in sentinel mice co-housed with the inoculated mice from the M. pinnipedii and M. bovis 04-303 groups, as evidenced by the recovery of viable M. pinnipedii and M. bovis from the lungs of sentinel mice. Mice inoculated with M. pinnipedii (1856) and M. bovis (534) survived until euthanized, whereas five of the M. bovis 04-303-inoculated mice died at 17 dpi. This study constitutes the first report of the transmissibility of a M. pinnipedii strain in mice and confirms the utility of this experimental model to study virulence features such as the transmission of poorly characterized MTC species.

[A Case of Repeat Pancreatectomy-Robotic Spleen-Preserving Distal Pancreatectomy after Robotic Pancreaticoduodenectomy].

Laparoscopic pancreaticoduodenectomy has been covered by insurance since 2016 in Japan, and advance laparoscopic and robotic pancreaticoduodenectomy has been also covered by insurance since 2020 in Japan. It has been reported that laparoscopic pancreatectomy causes few postoperative adhesions in the abdominal cavity and that repeat laparoscopic surgery could be performed. However, in robotic pancreatectomy, there have been no such reports yet. We reported that even after robotic pancreaticoduodenectomy, there were few adhesions in the abdominal cavity, and we were able to perform the robotic distal pancreatectomy with preservation of the splenic artery and vein. This suggested that robotic surgery was an effective treatment method for repeat pancreatectomy, given its low invasiveness and minimal adhesion.

High-Resolution Three-dimensional Whole-organ Tomography of Microbial Infections.

Most infections take place within three-dimensional host tissues with intricate anatomy and locally varying host physiology. The positioning of pathogen cells within this diverse environment significantly affects their stress levels, responses, fate, and contribution to the overall progression of the disease and treatment failure. However, due to the technical difficulties in locating µm-sized pathogen cells within cm-sized host organs, this area of research has been relatively unexplored. Here, we present a method for addressing this challenge. We employ serial two-photon tomography and AI-enhanced image analysis to locate individual Salmonella cells throughout the entire spleen, liver lobes, and whole lymph nodes of infected mice. Using fluorescent reporters and in vivo antibody administration, the replication rate of single Salmonella cells, their local interaction with specific immune cells, and bacterial responses to antibiotics can be determined. These methodologies open avenues for a comprehensive examination of infections, their prevention, and treatment within the three-dimensional tissue context.

Intravital imaging of splenic classical monocytes modifying the hepatic CX3CR1+ cells motility to exacerbate liver fibrosis via spleen-liver axis.

CX3CR1+ cells play a crucial role in liver fibrosis progression. However, changes in the migratory behavior and spatial distribution of spleen-derived and hepatic CX3CR1+ cells in the fibrotic liver as well as their influence on the liver fibrosis remain unclear. METHODS: The CX3CR1GFP/+ transgenic mice and CX3CR1-KikGR transgenic mice were used to establish the CCl4-induced liver fibrosis model. Splenectomy, adoptive transfusion of splenocytes, in vivo photoconversion of splenic CX3CR1+ cells and intravital imaging were performed to study the spatial distribution, migration and movement behavior, and regulatory function of CX3CR1+ cells in liver fibrosis. RESULTS: Intravital imaging revealed that the CX3CR1GFP cells accumulated into the fibrotic liver and tended to accumulate towards the central vein (CV) in the hepatic lobules. Two subtypes of hepatic CX3CR1+ cells existed in the fibrotic liver. The first subtype was the interacting CX3CR1GFP cells, most of which were observed to distribute in the liver parenchyma and had a higher process velocity; the second subtype was mobile CX3CR1GFP cells, most of which were present in the hepatic vessels with a faster moving speed. Splenectomy ameliorated liver fibrosis and decreased the number of CX3CR1+ cells in the fibrotic liver. Moreover, splenectomy rearranged CX3CR1GFP cells to the boundary of the hepatic lobule, reduced the process velocity of interacting CX3CR1GFP cells and decreased the number and mobility of mobile CX3CR1GFP cells in the fibrotic liver. Transfusion of spleen-derived classical monocytes increased the process velocity and mobility of hepatic endogenous CX3CR1GFP cells and facilitated liver fibrosis progression via the production of proinflammatory and profibrotic cytokines. The photoconverted splenic CX3CR1+ KikRed+ cells were observed to leave the spleen, accumulate into the fibrotic liver and contact with hepatic CX3CR1+ KikGreen+ cells during hepatic fibrosis. CONCLUSION: The splenic CX3CR1+ monocytes with classical phenotype migrated from the spleen to the fibrotic liver, modifying the migratory behavior of hepatic endogenous CX3CR1GFP cells and exacerbating liver fibrosis via the secretion of cytokines. This study reveals that splenic CX3CR1+ classical monocytes are a key driver of liver fibrosis via the spleen-liver axis and may be potential candidate targets for the treatment of chronic liver fibrosis.

Persistent disparities between trauma center types in the management of children with high-grade blunt splenic injuries.

BACKGROUND: In the early 2000s, substantial variations were reported in the management of pediatric patients with blunt splenic injury (BSI). The purpose of this study was to assess the recent trends and disparities between different types of trauma centers. We hypothesized that there would be persistent disparities despite decreased trends in the rate of splenectomy. METHODS: This is a retrospective cohort study using the American College of Surgeons Trauma Quality Improvement Program database. We included patients (age ≤18 years) with high-grade BSI (Abbreviated Injury Scale 3-5) between 2014 and 2021. The patients were divided into three groups based on trauma center types (adult trauma centers [ATCs], mixed trauma centers [MTCs], and pediatric trauma centers [PTCs]). The primary outcome was the splenectomy rate. Logistic regression was performed to evaluate the association between trauma center types and clinical outcomes. Additionally, the trends in the rate of splenectomy at ATCs, MTCs, and PTCs were evaluated. RESULTS: A total of 6601 patients with high-grade BSI were included in the analysis. Overall splenectomy rates were 524 (17.5%), 448 (16.3%), and 32 (3.7%) in the ATC, MTC, and PTC groups, respectively. ATCs and MTCs had significantly higher splenectomy rates compared to PTCs (ATCs: OR = 5.72, 95%CI = 3.78-8.67, and p < 0.001 and MTCs: OR = 4.50, 95%CI = 2.97-6.81, and p < 0.001), while decreased trends in the splenectomy rates were observed in ATCs and MTCs (ATCs: OR = 0.92, 95%CI = 0.87-0.97, and p = 0.003 and MTCs: OR = 0.92, 95%CI = 0.87-0.98, and p = 0.013). CONCLUSIONS: This study suggested persistent disparities between different trauma center types in the management of children with high-grade BSI.

Repeat imaging increases detection of delayed pseudoaneurysms in patients with high-grade solid organ injury following abdominal trauma.

BACKGROUND: Nonoperative management of abdominal trauma can be complicated by the development of delayed pseudoaneurysms. Early intervention reduces the risk of rupture and decreases mortality. The objective of this study is to determine the utility of repeat computed tomography (CT) imaging in detecting delayed pseudoaneurysms in patients with abdominal solid organ injury. METHODS: A retrospective cohort study reviewing Montreal General Hospital registry between 2013 and 2019. Patients with The American Association for the Surgery of Trauma (AAST) grade 3 or higher solid organ injury following abdominal trauma were identified. A chart review was completed, and demographics, mechanism of injury, Injury Severity Score (ISS) score, AAST injury grade, CT imaging reports, and interventions were collected. Descriptive analysis and logistic regression model were completed. RESULTS: We identified 195 patients with 214 solid organ injuries. The average age was 38.6 years; 28.2% were female, 90.3% had blunt trauma, and 9.7% had penetrating trauma. The average ISS score was 25.4 (SD 12.8) in patients without pseudoaneurysms and 19.5 (SD 8.6) in those who subsequently developed pseudoaneurysms. The initial management was nonoperative in 57.0% of the patients; 30.4% had initial angioembolization, and 12.6% went to the operating room. Of the cohort, 11.7% had pseudoaneurysms detected on repeat CT imaging within 72 h. Grade 3 represents the majority of the injuries at 68.0%. The majority of these patients underwent angioembolization. CONCLUSIONS: In patients with high-grade solid organ injury following abdominal trauma, repeat CT imaging within 72 h enabled the detection of delayed development of pseudoaneurysms in 11.7% of injuries. The majority of the patients were asymptomatic.

Oral subacute polypropylene microplastics administration effect on potential immunotoxicity in ICR mice.

Exposure to microplastics may be associated with damage of immune system. Polypropylene microplastics (PP-MPs) with a wide range of beneficial applications have not been extensively studied with respect to the immune system. The aim of this investigation is to examine the influence of two different sizes of PP-MPs (5.2 and 23.9 µm diameter) on immune system components in ICR mice. PP-MPs were administered orally to female and male mice at 0 (corn oil vehicle), 500, 1000, or 2000 mg/kg/d for single and daily for 4-week repeated toxicity test, respectively. No significant differences were observed in number of thymic CD4+, CD8+, CD4+CD8+ T lymphocytes, splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-γ to interleukin-4 in culture supernatants from activated splenocytes ex vivo (48 hr) was lower in females which were repeatedly administered with PP-MPs compared to vehicle irrespective of PP-MPs size and dose. In contrast, the opposite trend was observed in males. Production of tumor necrosis factor-α was upregulated in females that were repeatedly exposed to PP-MPs. The serum IgG2a/IgG1 ratio was lowered in female receiving large-size PP-MPs. Data suggest that immune disturbances resulting in predominant type-2 helper T cell reactivity may occur in mice, especially in females, when repeatedly exposed to PP-MPs. Further investigations with longer exposure periods are necessary to determine the immunotoxicities attributed to PP-MPs.

Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen.

Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. In the bone marrow, chronic stress induced a sustained transition from lymphoid to myeloid cells, accompanied by corresponding changes in gene expression. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J2, a lipid mediator that inhibits inflammation. In the spleen, chronic stress also induced a lymphoid-to-myeloid transition, albeit transiently, alongside gene expression changes indicative of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression.

Insights into Q-markers of honey-fried licorice in treating spleen deficiency based on substance and energy metabolism regulation.

BACKGROUND: Honey-fried Licorice (HFL) is a dosage form of Glycyrrhizae Radix et Rhizome processed with honey, which has been recorded to exhibit better efficacy in tonifying the spleen compared to the raw product. In contrast, different processing methods of Glycyrrhizae Radix et Rhizome exhibit different efficacies and applications, but their current quality control index components remain consistent. PURPOSE: Based on the discovery and research strategy of traditional Chinese medicine decoction piece quality marker (Q-marker), this study aimed to conduct a multidimensional integration of constituents absorbed into the body and metabolomics based on the tonifying spleen and stomach effects of HFL to effectively identify the Q-marker of HFL. METHODS: In this study, a spleen deficiency rat model was established using the "exhausted swimming + poor diet" method to investigate the pharmacodynamics of tonifying the spleen and stomach by HFL. The constituents absorbed into blood was conducted using UPLC-Q-TOF/MS, correlation analysis between metabolomics and constituents absorbed into blood recognized the Q-Marker of HFL. RESULTS: The pharmacodynamic data demonstrated that HFL exhibited a significant regulatory effect on the disordered levels of PP, trypsin, chymase, PL, α-Glu, MTL, GAS, VIP, IL-2, IFN-γ, and IgA in the spleen deficiency model. Furthermore, HFL was found to improve the pathological changes in the spleen and intestine in the spleen deficiency model, highlighting its significant "tonifying spleen and stomach" effect. In the serum containing HFL, a total of 17 constituents were identified as being absorbed into the blood. Among these, 11 were prototypical components, while 6 were metabolites. Metabolomics data revealed that 9 differentially expressed metabolic markers were observed. Furthermore, the analysis of endogenous metabolic markers indicated that 10 components exhibited significant correlations with these biomarkers. CONCLUSION: The effect of "tonifying spleen and stomach" of HFL is closely related to the regulation of the material and energy metabolism pathway. The Q-Marker of HFL is glycyrrhizic acid and 18ß-glycyrrhetinic acid as the main control standards and liquiritin, isoliquiritin, liquiritin, isoliquiritin, isolicorice flavonol, licorice chalcone C and Formononetin were used as auxiliary standards.

[Efficacy of navel application of Jianpiwenyang Gel for chronic diarrhea of spleen and stomach weakness type: a randomized controlled trial and analysis of the mechanism].

OBJECTIVE: To investigate the efficacy of Jianpiwenyang Gel (SSWYG) for treating chronic diarrhea and explore its therapeutic mechanism. METHODS: Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules (control group, n=40) or naval application with SSWYG (treatment group, n=40) for one week, after which symptoms of chronic diarrhea were evaluated. The Chinese medicine system pharmacology analysis platform (TCMSP), GeneCards, NCBI, OMIM database and GEO database (GSE14841) were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets. The key targets were obtained by topological analysis for Gene Ontology (GO) and KEGG analyses. The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software. RESULTS: In both groups, gastrointestinal symptom rating scale (GSRS), Bristol Scale and TCM syndrome scores significantly improved after the treatments (P < 0.05), and better effects were observed in the treatment group (P < 0.05). Sixtyeight targets of SSWYG in treating chronic diarrhea were obtained, and 33 most probable ones were screened out by topological analysis. GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways. Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3, JNK, IL1B, IL6, and AKT1. JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG. CONCLUSION: SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN, suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Dynamics of ex vivo cytokine transcription during experimental Toxocara canis infection in Balb/c mice.

The cytokine microenvironment is crucial in generating and polarizing the immune response. A means of monitoring this environment would be of great value for better understanding Toxocara canis immune modulation. The aim of this study was to analyze the dynamics of cytokine transcription ex vivo, during early (24-48 hours) and late (15-30 days) times post-infection, in the mesenteric lymph nodes, spleen and intestinal mucosa of Balb/c mice experimentally infected with T. canis larvae. Mice in the treated group were infected with 100 third-stage larvae (L3), whereas mice in the control group were not infected. Analyses were performed at different times: 24-48 hours post-infection (HPI), 15-30 days post-infection (DPI). IL4, IL10, IL12 and Ym1 mRNA transcriptions were analyzed through qPCR. This study showed cytokine transcription mediated by migrating larvae in the mesenteric lymph nodes and spleen at 24-48 HPI, whereas cytokine transcription in the intestinal mucosa was observed only at late times (15-30 DPI). These results suggest that the T. canis larvae migration during infection might play a role in cytokine dynamics. Since the cytokine microenvironment is crucial in modulating immune response, knowledge of cytokine dynamics during T. canis infections pave the way to better understand its interaction with the host.

Trauma to the solid abdominal organs: The missed dark box of colonoscopy.

Colonoscopy is an integral part of the lower bowel care and is generally considered a potentially safe diagnostic and therapeutic procedure performed as a daycare outpatient procedure. Colonoscopy is associated with different complications that are not limited to adverse events related to the bowel preparation solutions used, the sedatives used, but to the procedure related as well including bleeding and perforation. Injuries to the extra-luminal abdominal organs during colonoscopy are uncommon, however, serious complications related to the procedure have been reported infrequently in the literature. Life threatening injuries to the spleen, liver, pancreas, mesentery, and urinary bladder have been reported as early as in mid-1970s. These injuries should not be overlooked by clinicians and endoscopists. Steadily increasing abdominal pain, abdominal distension, and hemodynamic instability in absence of rectal bleeding should raise the possibility of severe organ injury. Splenic and hepatic injury following colonoscopy are usually serious and may be life threatening. Although conservative management may help, yet they usually need interventional radiology or surgical intervention. Acute pancreatitis following colonoscopy is usually mild and is mostly managed conservatively. The mechanism of abdominal organ injuries during colonoscopy is not fully understood, however many risk factors have been identified, which can be classified as- organ related, procedure related, and local abdominal factors. Difficult colonoscopy and prior intra-abdominal adhesions are probably the most relevant risk factors for these injuries. Left lateral position, avoidance of looping and excessive force during the procedure would probably reduce the risk of such injuries.