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Objective: To observe the clinical effect of the row-like needling along the spleen meridian combined with autonomous functional exercise in treatment of postpartum diastasis recti abdominis., Methods: A total of 72 patients with postpartum diastasis recti abdominis were randomly divided into an observation group (36 cases, 3 cases excluded) and a control group (36 cases, 3 cases dropped out). In the control group, the autonomous functional exercise was performed on the rectus abdominis. In the observation group, on the basis of the treatment as the control group, the row-like needling along the spleen meridian was delivered. Along the distribution of the spleen meridian on the abdomen, besides Daheng (SP 15), acupuncture was operated at the sites 3 cm and 6 cm directly above and below Daheng (SP 15) bilaterally. Five points on each side were stimulated along the meridian. Acupuncture was delivered once every two days, 3 interventions a week. One course of treatment, composed of 10 treatments, was required. Before treatment and after 5 and 10 treatments, the inter-rectus distance (IRD) and the score of the medical outcomes study 36-item short form health survey (SF-36) were observed in the two groups, respectively., Results: After 5 and 10 treatments, the IRD at the sites 3 cm above the umbilicus, in the center of the umbilicus and below the umbilicus was reduced when compared with that before treatment in the observation group, respectively ( P <0.01); and the IRD at the site 3 cm above the umbilicus was decreased in comparison with that before treatment in the control group ( P <0.05). After treated for 5 times, compared with the control group, the IRD at the site 3 cm below the umbilicus was reduced in the observation group ( P <0.05); and after treated for 10 times, compared with the control group, the IRD at the sites 3 cm above the umbilicus, in the center of the umbilicus and below the umbilicus was reduced in the observation group ( P <0.01). After the completion of 5 and 10 treatments, the scores of physical functioning (PF), role-physical (RP), role-emotional (RE) and health change (HC), as well as the total score of SF-36 were all higher than those before treatment in the observation group ( P <0.01); while in the control group, the scores of PF, RP and RE, as well as the total score of SF-36 were increased in comparison with those before treatment ( P <0.01). After 5 treatments, the scores of general health (GH) and HC in the observation group were higher than those of the control group ( P <0.05, P <0.01); and after 10 treatments, the score of PF, GH and HC, as well as the total score of SF-36 in the observation group were higher than those of the control group ( P <0.01)., Conclusion: On the basis of autonomous functional exercise, the row-like needling along the spleen meridian can promote the recovery of postpartum diastasis recti abdominis and improve the quality of life of the patients.

Plasmodium vivax contributes significantly to global malaria morbidity. Key advances include the discovery of pathways facilitating invasion by P. vivax merozoites of nascent reticulocytes, crucial for vaccine development. Humanized mouse models and hepatocyte culture systems have enhanced understanding of hypnozoite biology. The spleen has emerged as a major reservoir for asexual vivax parasites, replicating in an endosplenic life cycle, and contributing to recurrent and chronic infections, systemic inflammation, and anemia. Splenic accumulation of uninfected red cells is the predominant cause of anemia. Recurring and chronic infections cause progressive anemia, malnutrition, and death in young children in high-transmission regions. Endothelial activation likely contributes to vivax-associated organ dysfunction. The many recent advances in vivax pathobiology should help guide new approaches to prevention and management., Competing Interests: Declaration of interests G.D.S. is an unpaid consultant to GSK on tafenoquine. All other authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare the clinical effect of intradermal needling and acupuncture in prevention and treatment of leukopenia after chemotherapy with spleen-kidney deficiency., Methods: A total of 90 patients with malignant tumor who received chemotherapy were randomly divided into a intradermal needling group (30 cases, 1 case dropped out), an acupuncture group (30 cases, 2 cases dropped out, 1 case was eliminated) and a control group (30 cases). The control group received conventional symptomatic treatment after chemotherapy. On the basis of the treatment in the control group, the intradermal needling group received intradermal needling at Guanyuan (CV 4), Dazhui (GV 14) and bilateral Geshu (BL 17), Zusanli (ST 36)，Shenshu (BL 23), the needles were retained for 48 h, once every other day. On the basis of the treatment in the control group, the acupuncture group received conventional acupuncture at the same acupoints as the intradermal needling group, once every other day. The treatment started from the first day of chemotherapy, for a total of 2 weeks in the three groups. The white blood cell count, neutrophil count, hemoglobin content, platelet count and Karnofsky performance status (KPS) score before treatment and on 3rd, 7th, 14th, and 21st days after treatment were compared among the three groups. The incidence and grading of leukopenia and the usage of leukocyte-boosting drug during chemotherapy cycle was recorded., Results: On 7th day after treatment, the white blood cell count in the intradermal needling group and the acupuncture group was higher than that in the control group ( P <0.01, P <0.05). On the 14th day after treatment, the hemoglobin content in the intradermal needling group and the acupuncture group was higher than that in the control group ( P <0.01). On the 7th, 14th, and 21st days after treatment, the platelet count in the acupuncture group was higher than that in the control group ( P <0.01), on the 14th and 21st days after treatment, the platelet count in the intradermal needling group was higher than that in the control group ( P <0.01). There was no statistically significant difference among the three groups after treatment in terms of neutrophil count, KPS score, incidence and grading of leukopenia, and the usage of leukocyte-boosting drug ( P >0.05)., Conclusion: Both intradermal needling and acupuncture can effectively increase peripheral blood white blood cell count, hemoglobin content and platelet count during chemotherapy cycle, reduce the toxicity of chemotherapy drug to bone marrow hematopoietic function, and alleviate bone marrow suppression after chemotherapy. The two treatments are equally effective.

Splenic hemorrhagic shock is a typical emergency in surgery, seriously threatening human beings' life. Emerging evidence shows that microRNAs (miRNAs) are closely related to inflammation and immunity in the body. However, the detailed effects and underlying mechanisms of miRNAs on the immune function of splenic hemorrhagic shock have not been revealed yet. In the present study, we construct the rat hemorrhagic shock model, and the rats are further cured with splenic blood transport clipping recanalization (SBTCR). MiR-18b-5p was highly expressed in the spleen of hemorrhagic shock rats detected by the qRT-PCR assay. Functionally, down-regulation of miR-18b-5p notably inhibited the levels of SOD1, iNOS and IL-6 in macrophages isolated from splenic tissues detected by qRT-PCR and ELISA assays. In addition, inhibition of miR-18b-5p significantly decreased the M1/M2 ratio of macrophages. Besides, knockdown of miR-18b-5p obviously reduced the Th1/Th2 ratio of CD4 + T cells. Moreover, HIF-1α was predicted as a target gene of miR-18b-5p, which was further confirmed by dual-luciferase reporter assay, and HIF-1α was negatively associated with miR-18b-5p. Furthermore, overexpression of HIF-1α partially restored the effects of miR-18b-3p on inflammation and immunity in macrophages. Taken together, miR-18b-5p may be a novel therapeutic candidate target in splenic hemorrhagic shock treatment., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction can cause recurrent portal hypertension (PH)-related complications such as ascites and gastroesophageal variceal bleeding. Portography is invasive and costly limits its use as a screening modality., Purpose: To assess the clinical value of conventional ultrasound in combination with point shear wave elastography (pSWE) to predict TIPS dysfunction., Material and Methods: A total of 184 patients with cirrhosis scheduled for TIPS implantation were enrolled in this study and evaluated retrospectively. The splenoportal venous blood flow parameter, liver stiffness (LS), and spleen stiffness (SPS) were measured. Outcome measures included differences in portal vein velocity (PVV), splenic vein velocity (SPVV), LS, and SPS. The accuracy of change in PVV (ΔPVV), SPVV (ΔSPVV), and SPS (ΔSPS) to diagnose TIPS dysfunction was investigated., Results: TIPS dysfunction occurred in 28 of 184 patients (15.2%). Eighteen (64.3%) patients had shunt stenoses and 10 (35.7%) had shunt occlusion. Portal vein diameter (PVD), PVV, splenic vein diameter (SPVD), SPVV, LS, and SPS were not significantly different between the TIPS normal and TIPS dysfunction groups. Compared with the TIPS normal group, PVV and SPVV of the TIPS dysfunction group decreased significantly, whereas SPS increased significantly ( P  < 0.001). The values of areas under the receiver operating characteristic curves of ΔPVV, ΔSPVV, and ΔSPS for the diagnosis of TIPS dysfunction were 0.97, 0.96, and 0.87, respectively., Conclusion: pSWE showed a diagnostic efficacy comparable to conventional ultrasound for diagnosing TIPS dysfunction and can be used routinely after TIPS procedures.

The underlying mechanism of electroacupuncture (EA) in relieving obesity, anti-inflammation and the interaction with metabolic pathways in obese mice has not been elaborated. The aim of this study was to investigate the regulation of EA on macrophage polarization in obesity tissue of diet-induced obesity mice. Mice were divided in 6 groups: normal control group, model group, EA-7 group, EA-14 group, EA-21 group and EA-28 group. Low-frequency EA was applied at "Tianshu (ST 25)", "Guanyuan (CV 4)", "Zusanli (ST 36)" and "Sanyinjiao (SP 6)" for 10 min. Adipose tissue was assessed with hematoxylin and eosin staining. Adipocytokines and pro-inflammatory factors expression was measured by ELISA. The protein and mRNA levels of macrophage markers were examined by immumohistochemical staining and RT-PCR, respectively. EA treatment was associated with a decrease of adipose tissue and large adipocytes, and an increase of small adipocytes. After EA treatment, the levels of Leptin, Chemerin, TNF-α, F4/80, iNOS, and CD11c decreased obviously in adipose tissue, while IL-4, IL-10 and CD206 levels increased significantly. Besides, TNF-α in spleen tissue was also downregulated, but IL-4 and IL-10 were upregulated. EA prevents weight gain through modulation inflammatory response and macrophage polarization in obese adipose tissues., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction : NAFLD is often under-diagnosed, even though rates of its co-morbidities such as obesity and type2 diabetes mellitus, prominent statuses of inflammation, are significantly high. The spleen-liver axis is gaining much credit in the last years like other well-known organ axes. Areas covered : PubMed/MEDLINE was searched for relevant articles related to concomitant occurrence of NAFLD and spleen. Areas covered in this review include: (1) updated findings of spleen dimensions at ultrasonography, (2) discussion of current data on pathophysiological connections between obesity-related NAFLD and increased volume of the spleen, and (3) analysis of current immune-mediated mechanisms characterizing the so.called chronic low-grade inflammation leading to insulin resistance. Expert opinion : The advances in explaining mechanisms underlying the spleen involvement in immune regulation, coupled with research about the role of spleen in NAFLD, could impact real world outcomes through establishing better tools for a precocious diagnosis. Using both liver and spleen ultrasonography, technique largely dealt with in this review, could expand the possibility to cover an adequate diagnostic path toward NAFLD, reaching a good sensibility and specificity.

Background: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder caused by dysfunction at the neuromuscular junction spreads. The main clinical features of this disease are fluctuating fatigue, and weakness of the skeletal muscles of the eyes and limbs. At present, the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine has been widely used for MG. The present study was conducted to evaluate the efficacy and safety of the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine for MG., Methods: The following 10 databases were searched from inception to March 2021: PubMed, Cochrane Library, EMBASE, Web of Science, Springer, China National Knowledge Infrastructure (CNKI), Wan fang, VIP Chinese Science and Technique Journals Database, the Chinese Bio Medical Database (CBM), and Baidu Scholar. The language was limited to the Chinese and English language. Merely randomized controlled trials (RCTs) were included. The Cochrane Collaboration risk-of-bias tool was used for the methodological quality assessment and risk of bias. The meta-analysis was assessed using the Cochrane RevMan 5.3 software., Results: In the present study, a meta-analysis was conducted, and RCTs that met the eligibility criteria were included. Furthermore, the different outcome indicators of different methods were objectively compared. The main outcome indicators included the effective rate, quantitative myasthenia gravis (QMG) scores, adverse events, and quality of life (QOL). The secondary outcome indicators included AchRAb, serum-related immune cells (such as CD3+CD4+cells and CD4+/CD8+cells), the traditional Chinese medicine syndrome score scale (TCMSSS), the serum interleukin-6 level, the level of IFN-γ and its mRNA, and the clinical score that contains the clinical absolute score (CAS) and clinical relative score (CRS)., Conclusion: This study would provide credible evidence to determine whether the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine is an effective treatment method for MG., Trial Registration Number: INPLASY202110097., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown whether gut microbiota provide signals that dynamically regulate distal immune responses following an extra-gastrointestinal infection. We show here that gut bacteria composition correlated with the severity of malaria in children. Using the murine model of malaria, we demonstrate that parasite burden and spleen germinal center reactions are malleable to dynamic cues provided by gut bacteria. Whereas antibiotic-induced changes in gut bacteria have been associated with immunopathology or impairment of immunity, the data demonstrate that antibiotic-induced changes in gut bacteria can enhance immunity to Plasmodium. This effect is not universal but depends on baseline gut bacteria composition. These data demonstrate the dynamic communications that exist among gut bacteria, the gut-distal immune system, and control of Plasmodium infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3 + and CD4 + lymphocytes, and CD68 + and CD206 + macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4 + lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.

The spleen serves as a blood volume reservoir for systemic volume regulation in heart failure (HF) patients. Changes are seen in spleen size in advanced HF patients after left ventricular assist device (LVAD) implantation. The pulsatility index (PI) is an indicator of native heart contractility with hemodynamic changes in patients using LVAD. We hypothesized that the splenic volume was associated with the PI, reflecting the hemodynamics in advanced HF patients with LVADs. Herein, we investigated the relationship between splenic volume and PI in these patients. Forty-four patients with advanced HF underwent implantation of HeartMate II ® (Abbott, Chicago, IL, USA) as a bridge to heart transplantation at the Nagoya University Hospital between October 2013 and June 2019. The data of 27 patients (21 men, median age 46 years) were analyzed retrospectively. All patients underwent blood tests, echocardiography, right heart catheterization, and computed tomography (CT). Spleen size was measured via CT volumetry; the splenic volume (median: 190 mL) correlated with right arterial pressure ( r  = 0.431, p  = 0.025) and pulmonary capillary wedge pressure ( r  = 0.384, p  = 0.048). On multivariate linear regression analysis, the heart rate (β = -0.452, p  = 0.003), pump power (β = -0.325, p  = 0.023), and splenic volume (β = 0.299, p  = 0.038) were independent determinants of PI. The splenic volume was associated with PI, reflecting the cardiac preload in advanced HF patients with LVADs. Thus, spleen measurement using CT may help estimate the systemic volume status and understand the hemodynamic conditions in LVAD patients.

Background: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction., Methods: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13)., Results: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm 3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05)., Conclusions: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

Objective: To investigate the therapeutic effect of the Jianpi Liqi Fang ( ，JPLQF) combined with transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and spleen deficiency syndrome (SDS) and identify a potential indicator of efficacy., Methods: Ninety-nine patients with HCC who were diagnosed with SDS, non-spleen deficiency syndrome (NSDS), or no syndrome (NS) were treated with JPLQF combined with TACE for three periods. Therapeutic efficacy was compared among the groups. Plasma proteins were screened using label-free discovery analysis and verified via enzyme-linked immunosorbent assay (ELISA). Furthermore, receiver operating characteristic (ROC) curves were analyzed to evaluate therapeutic indicators., Results: After treatment, the Karnofsky Performance Status was significantly improved in the SDS group and significantly better than that in the NS group. The Traditional Chinese Medicine (TCM) syndrome scores were lower in the SDS group after treatment and lower than those in the NSDS group. However, alanine aminotransferase, carbohydrate antigen 19-9, alpha-fetoprotein, and carcinoembryonic antigen levels and white blood cell and platelet counts did not differ among the groups. Serum aspartate aminotransferase levels in the SDS group were significantly lower after treatment than before treatment, and total bilirubin levels were significantly lower in the SDS group than in the NSDS group. Label-free analysis identified 24 differentially expressed proteins (DEPs) between the SDS and NS groups, including 17 and 7 upregulated and downregulated proteins, respectively. Fibulin-5 (FBLN5) displayed the largest difference in expression between the groups. ELISA confirmed that FBLN5 levels were significantly lower in the NSDS and NS groups than in the SDS group. Following treatment with JPLQF and TACE, FBLN5 expression was upregulated only in the SDS group. Furthermore, ROC curve analysis indicated that FBLN5 may serve as a potential indicator of the efficacy of JPLQF combined with TACE in patients with HCC and SDS., Conclusion: JPLQF combined with TACE improved quality of life, clinical TCM symptoms, and liver function in patients with HCC and SDS. FBLN5 expression was significantly altered by treatment with JPLQF and TACE in patients with HCC and SDS.

Organophosphate pesticides as diazinon disrupt the neuroimmune communication, affecting the innate and adaptive immune response of the exposed organisms. Since the target molecule of diazinon is typically the acetylcholinesterase enzyme (AChE), the existence of a non-neuronal cholinergic system in leukocytes makes them susceptible to alterations by diazinon. Therefore, the aim of this work was to evaluate the activity of AChE, acetylcholine (ACh) concentration, and the expression of nicotinic ACh receptors (nAChR) and muscarinic ACh receptors (mAChR) in spleen mononuclear cells (SMNC) of Nile tilapia (O. niloticus) exposed in vitro to diazoxon, a diazinon metabolite. SMNC were exposed in-vitro to 1 nM, 1 μM, and 10 μM diazoxon for 24 h. The enzyme activity of AChE was then evaluated by spectrophotometry, followed by ACh quantification by ultra-performance liquid chromatography. Finally, mAChR and nAChR expression was evaluated by RT-qPCR. The results indicate that AChE levels are significantly inhibited at 1 and 10 μM diazoxon, while the relative expression of (M3, M4, and M5) mAChR and (β2) nAChR is reduced significantly as compared against SMNC not exposed to diazoxon. However, ACh levels show no significant difference with respect to the control group. The data indicate that diazoxon directly alters elements in the cholinergic system of SMNC by AChE inhibition or indirectly through the interaction with AChR, which is likely related to the immunotoxic properties of diazinon and its metabolites., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Intraportal injection is regarded as the current standard procedure of hepatocyte transplantation (HTx). In islet transplantation, which shares many aspects with HTx, recent studies have clarified that instant blood-mediated inflammatory reaction (IBMIR), characterized by strong innate immune responses, can cause poor engraftment, so other transplant sites to avoid such a reaction have been established. Although IBMIR was reported to occur in HTx, few reports have evaluated alternative transplant sites for HTx. In this study, we sought to determine the optimum transplant site for HTx. Rat hepatocytes (1.0 × 10 7 ) were transplanted at the 9 transplant sites (intraportal (IPO), intrasplenic (IS), liver parenchyma, subcutaneous, intraperitoneal, renal subcapsular, muscle, inguinal subcutaneous white adipose tissue, and omentum) of analbuminemic rats. The serum albumin levels, immunohistochemical staining (albumin, TUNEL, and BrdU), and in vivo imaging of the grafts were evaluated. The serum albumin levels of the IPO group were significantly higher than those of the other groups ( p < .0001). The BrdU-positive hepatocyte ratio of liver in the IS group (0.9% ± 0.2%) was comparable to that of the IPO group (0.9% ± 0.3%) and tended to be higher than that of the spleen in the IS group (0.5% ± 0.1%, p = .16). Considering the in vivo imaging evaluation and the influence of splenectomy, the graft function in the IS group may be almost entirely achieved by hepatocytes that have migrated to the liver. The present study clearly showed that the intraportal injection procedure is more efficient than other procedures for performing HTx.

Objectives: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications. Little is known about the ability of spleen stiffness (SS) for predicting the survival of cirrhotic patients undergoing TIPS. This study is to evaluate the influence of SS detected by point shear wave elastography (pSWE) in predicting survival after TIPS., Methods: This retrospective cohort study screened consecutive patients who underwent TIPS and reliable pSWE measurement between October 2014 and September 2017 from our prospectively maintained database. SS values were measured before TIPS. The primary endpoint was the overall survival after TIPS. The Cox regression analysis model was used for univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to calculate the sensitivity, specificity, and positive and negative predictive values., Results: A total of 89 patients were involved in the final analysis. 24 patients (27.0%) died during a median follow-up time of 31 m. Multivariable Cox regression analysis confirmed that higher SS value ( P < 0.001), LS value ( P = 0.008), diameter of shunt ( P = 0.001), and older age ( P < 0.001) were independent prognostic factors of survival after TIPS. The risk of death rose 57.440-fold for each SS unit (m/s) increase. SS was also correlated with liver failure after TIPS. ROC analysis showed that the best SS cutoff value was 3.60 m/s for predicting survival, with a sensitivity of 54.2% and specificity of 90.8%., Conclusions: The SS value determined by pSWE in cirrhotic patients was an independent predictive factor for survival after TIPS., Competing Interests: The authors declare that there are no conflicts of interest in this study., (Copyright © 2020 Hao Zhu et al.)

Inflammation is a sophisticated biological tissue response to both extrinsic and intrinsic stimuli. Although the pathological aspects of inflammation are well appreciated, there are still rooms for understanding the physiological functions of the inflammation. Recent studies have focused on mechanisms, context and the role of physiological inflammation. Besides, there have been progress in the comprehension of commensal microbiota, immunometabolism, cancer and intracellular signaling events' roles that impact on the regulation of inflammation. Despite the fact that inflammatory responses are vital through tissue damage, understanding the mechanisms to turn off the finished or unnecessary inflammation is crucial for restoring homeostasis. Inflammation seems to be a smart process that acts like two edges of a sword, meaning that it has both protective and deleterious consequences. Knowing both edges and the regulation processes will help the future understanding and therapy for various diseases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Previous studies have used signal intensity (SI) to reflect liver function. However, few studies have evaluated liver function via the portal vein. Regarding the SI of the liver, spleen, and portal vein, no study has indicated which can best reflect liver function. Therefore, the aim of this study is to investigate whether these parameters can evaluate liver function in patients with cirrhosis and determine which is the best parameter., Methods: 120 patients with normal livers (n = 41) or Child-Pugh class A (n = 50), B (n = 21) or C (n = 8) disease who had undergone Gd-EOB-DTPA-enhanced MRI were retrospectively reviewed. Comparisons of the MRI data (liver parenchyma SI, portal vein SI, and spleen SI and liver-to-portal vein contrast ratio (LPC), liver-to-spleen contrast ratio (LSC), and portal vein-to-spleen contrast ratio (PSC)) in the 15-min hepatobiliary phase images were performed among the groups, and the correlations among the liver function parameters (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, platelet count, prothrombin time and international normalized ratio), liver function scores and MRI data were also quantitatively analysed., Results: Significant differences were observed in the liver parenchyma SI, LPC and LSC among the groups. These values all decreased gradually from normal livers to Child-Pugh class C cirrhotic livers (P < 0.001). The portal vein SI constantly and slightly increased from normal livers to Child-Pugh class C cirrhotic livers, but no differences were found among the groups in the portal vein SI and PSC (P > 0.05). LPC showed a stronger correlation with the Child-Pugh score and MELD score than LSC and the liver parenchyma SI. The order of the AUCs of these parameters, from largest to smallest, was as follows: LPC, LSC, and liver parenchyma SI (P > 0.05)., Conclusion: The liver parenchyma SI, LSC and LPC may be used as alternative imaging biomarkers to assess liver function, while the portal vein SI and PSC do not reflect liver function. Furthermore, LPC values can more effectively distinguish severity among patients with cirrhosis than the liver parenchyma SI and LSC.

Red pulp macrophages (RPMs) of the spleen mediate turnover of billions of senescent erythrocytes per day. However, the molecular mechanisms involved in sequestration of senescent erythrocytes, their recognition, and their subsequent degradation by RPMs remain unclear. In this study, we provide evidence that the splenic environment is of substantial importance in facilitating erythrocyte turnover through induction of hemolysis. Upon isolating human spleen RPMs, we noted a substantial lack of macrophages that were in the process of phagocytosing intact erythrocytes. Detailed characterization of erythrocyte and macrophage subpopulations from human spleen tissue led to the identification of erythrocytes that are devoid of hemoglobin, so-called erythrocyte ghosts. By using in vivo imaging and transfusion experiments, we further confirmed that senescent erythrocytes that are retained in the spleen are subject to hemolysis. In addition, we showed that erythrocyte adhesion molecules, which are specifically activated on aged erythrocytes, cause senescent erythrocytes to interact with extracellular matrix proteins that are exposed within the splenic architecture. Such adhesion molecule-driven retention of senescent erythrocytes under low shear conditions was found to result in steady shrinkage of the cell and ultimately resulted in hemolysis. In contrast to intact senescent erythrocytes, the remnant erythrocyte ghost shells were prone to recognition and breakdown by RPMs. These data identify hemolysis as a key event in the turnover of senescent erythrocytes, which alters our current understanding of how erythrocyte degradation is regulated., (© 2020 by The American Society of Hematology.)

A syndrome (Zheng in Chinese) plays a critical role in disease identification, diagnosis, and treatment in traditional Chinese medicine (TCM). Clinically, the liver Qi stagnation and spleen deficiency syndrome (LQSSDS) is one of the most common syndrome patterns. Over the past few decades, several animal models have been developed to understand the potential mechanisms of LQSSDS, but until now, simulation of the syndrome is still unclear. Recently, several studies have confirmed that an animal model combining a disease and a syndrome is appropriate for simulating TCM syndromes. Overlapping previous studies have reported that depression is highly associated with LQSSDS; hence, we attempted to develop a rat model combining depression and LQSSDS. We exposed the rats to different durations of chronic unpredictable mild stress (CUMS). Subsequently, the evaluation indicators at macrolevel consisted of behavioral tests including open field test, sucrose preference test, and forced swim test, food intake, body weight, white adipose tissue, fecal water content, visceral hypersensitivity, and small bowel transit, and the evaluation indicators at microlevel included changes of hypothalamic-pituitary-adrenal axis. Serum D-xylose absorption was used to comprehensively confirm and assess whether the model was successful during the CUMS-induced process. The results showed that rats exposed to 6-week CUMS procedure exhibited significantly similar traits to the phenotypes of LQSSDS and depression. This study provided a new rat model for the LQSSDS and could potentially lead to a better understanding of the pathophysiology of LQSSDS and the development of new drugs for this syndrome., (© 2020 American Association for Anatomy.)

Asplenia and hyposplenia (a/hyposplenia) are associated with increased morbidity and mortality from complications including infection. The recommended measures to reduce the risks associated with infection include patient education, vaccination and early initiation of antibiotic therapy for fever. Despite these recommendations, there is poor adherence to best practice management of patients with asplenia or hyposplenia (PWA/H). We present the development methodology and pilot data of a quality improvement project that explored whether a programme involving a novel medical alert card together with a patient and healthcare provider educational booklet increased vaccination rates and improved awareness and understanding of the infectious implications of a/hyposplenia. Our aim was to increase the proportion of those appropriately vaccinated and the proportion of patients with proper understanding of fever management by twofold in 18 months. Questionnaires were used locally as a root-cause-analysis to confirm the need for education and evaluate the effectiveness of the programme, as well as patient satisfaction. An interdisciplinary team developed a toolkit composed of a medical alert card and booklet. The toolkit was distributed to PWA/H who presented for a haematology clinic visit at a tertiary care centre. A separate set of questionnaires was then used to evaluate satisfaction and obtain feedback from patients and practitioners receiving the toolkit for the first time. Changes suggested by patients and practitioners with unanimous agreement among study investigators were made to the toolkit. The pilot study showed an increase in vaccination rates and awareness of vaccination status and appropriate fever management. The majority of the patients and practitioners found the information provided by the toolkit helpful. Given these promising single-centre findings, the intervention is being extended to another tertiary care centre with a large red blood cell disorders programme to evaluate its generalisability. The next step will be to expand the scope to paediatric PWA/H., Competing Interests: Competing interests: MS reports peer-reviewed grants for unrelated studies from Association of Hemophilia Clinic Directors of Canada Shire and Hemostasis and Thrombosis Research Society; unrestricted grants for unrelated studies from Octapharma, Amgen, Shire and Roche; personal fees from Novartis advisory board, Octapharma advisory board and Bayer advisory board. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The efficacy of prior activation of an anti-inflammatory pathway called the cholinergic anti-inflammatory pathway (CAP) through vagus nerve stimulation (VNS) has been reported in renal ischemia-reperfusion injury models. However, there have been no reports that have demonstrated the effectiveness of VNS after injury. We investigated the renoprotective effect of VNS in a cisplatin-induced nephropathy model. C57BL/6 mice were injected with cisplatin, and VNS was conducted 24 hours later. Kidney function, histology, and a kidney injury marker (Kim-1) were evaluated 72 hours after cisplatin administration. To further explore the role of the spleen and splenic macrophages, key players in the CAP, splenectomy, and adoptive transfer of macrophages treated with the selective α7 nicotinic acetylcholine receptor agonist GTS-21 were conducted. VNS treatment significantly suppressed cisplatin-induced kidney injury. This effect was abolished by splenectomy, while adoptive transfer of GTS-21-treated macrophages improved renal outcomes. VNS also reduced the expression of cytokines and chemokines, including CCL2, which is a potent chemokine attracting monocytes/macrophages, accompanied by a decline in the number of infiltrating macrophages. Taken together, stimulation of the CAP protected the kidney even after injury in a cisplatin-induced nephropathy model. Considering the feasibility and anti-inflammatory effects of VNS, the findings suggest that VNS may be a promising therapeutic tool for acute kidney injury.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by excessive fat accumulation in the liver. One of the underlying pathophysiological mechanisms is insulin resistance (IR). Traditional Chinese medicine (TCM) has showed potential benefits in the management of NAFLD. Lingguizhugan decoction (LGZG) is a representative Chinese herbal formula; however, there is still no rigorous clinical trial supporting its application., Methods/design: This study will be a three-arm, dose-optimization, randomized, double-blinded, placebo-controlled clinical trial. A total of 243 patients with NAFLD will be recruited and randomly assigned to the standard dose LGZG (SLGD) group, low dose LGZG (LLGD) group, or the placebo group based on a ratio of 1:1:1. The treatment period will be 12 weeks and the follow-up period will last 4 weeks. The primary outcome will be the proportions of participants with at least a 1-unit decrease of HOMA-IR from baseline to 12 weeks. Secondary outcomes will include the changes of body weight, body mass index, liver function, blood lipid metabolism, blood glucose metabolism, inflammatory responses, liver-kidney echo ratio by ultrasound, and various scales. Biological samples will also be collected for future researches on mechanism exploration., Discussion: This study will provide initial evidence regarding the efficacy and safety of LGZG in the treatment of NAFLD with spleen-yang deficiency pattern and promote its application in community healthcare centers. In addition, potential mechanisms will be explored based on studies of oral and gut microbiota., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800014364. Registered on 1 January 2018. The final protocol version was V3.0.

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years. However, the quality control (QC) standards of SJZD are insufficient. Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formula rapidly. In this study, we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC. A total of 56 compounds in SJZD were characterized in vitro, and 23 compounds were discovered in vivo. A total of 58 biomarkers were related to SQDS, and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status. A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy. We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng; dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria; glycyrrhizic acid, isoglabrolide, and glycyrrhetnic acid as the q-markers of licorice; and 2-atractylenolide as the q-marker of macrocephala. According to the discovery of the SJZD q-markers, we can establish the quality standard that is related to efficacy.

Objective: To evaluate noninvasively the severity of esophageal varices (EV) in cirrhotic patients using splenic hemodynamics obtained with dual-energy CT., Methods: We retrospectively analyzed 72 cirrhotic patients with EV between December 2018 and June 2019. Patients were divided into three groups: mild (EV1), medium (EV2), or severe (EV3) EV groups based on severity of EV assessed by endoscopy. An additional control group included 20 patients with normal liver CT. All patients underwent contrast-enhanced dual-energy CT. The iodine weight in spleen (IW-S) was calculated as IW-S = IC-S (iodine concentration in spleen) × V-S (spleen volume). Differences between EV and control groups were analyzed using one-way analysis of variance with Welch's correction. Games-Howell test made further pairwise comparison. The diagnostic value of IW-S on high-risk EV (EV2, EV3, or EV1 with red color sign) was evaluated using the ROC curve. p < 0.05 indicated statistical significance., Results: The overall difference of IW-S between the control and EV groups was statistically significant (p < 0.001). Patients with more severe EV had higher IW-S values. Pairwise comparisons showed that except for control vs. EV1 groups, the IW-S between any other two groups was significantly different (p < 0.05). With a cutoff value at 1087 mg, the AUC for using IW-S for the detection of high-risk EV was 0.87 (95% CI 0.77~0.94). Sensitivity and specificity were 84.9% and 84.2%, respectively., Conclusion: IW-S obtained with dual-energy CT can noninvasively predict EV severity., Key Points: • A higher iodine weight in spleen (IW-S) was observed in case of severe esophageal varices. • Cirrhotic patients have significantly higher IW-S than normal-liver patients. • IW-S in dual-energy CT maybe used to evaluate the severity of EV.

Purpose: The aim of the study was to test the feasibility of spleen stiffness measurement (SSM) by two-dimensional shear wave elastography (2D-SWE) and compare data on its diagnostic use with upper gastrointestinal endoscopy in children with extrahepatic portal hypertension (EHPH) before and after surgery., Methods: A total of 44 children were included in this study [34 children with EHPH (main group)] and 10 controls (7.57 ± 1.22 years), who underwent ultrasonography including SSM by 2D-SWE. Patients in the main group also underwent upper gastrointestinal endoscopy (UGE) and CT angiography. The main group was divided into three subgroups: Group A: patients with EHPH without large spontaneous portosystemic shunts (n = 15); Group B: patients with EHPH with large spontaneous portosystemic shunts (n = 9); Group C: patients with EHPVO and after surgical portosystemic shunts (n = 10)., Results: According to UGE, children in group A had significantly higher grades of esophageal varices (EV) (2.3 ± 0.14; p < 0.001) compared to those in groups B and C. After surgical shunting procedures (in group C), the grade of EV declined to 0.37 ± 0.14. There was significant difference (p < 0.001) in the mean SS of children in group A (70 ± 4.64 kPa) compared to those in group B (37.04 ± 4.62 kPa) and group C (26.3 ± 2.9 kPa). After surgery, SS decreased but remained elevated compared with controls (26.3 ± 2.9 vs 17.85 ± 1.3 kPa; p = 0.016). The SS showed a small but significant correlation with grades of EV (r = 0.56, p = 0.002)., Conclusions: The SS measured by 2D-SWE is feasible in children with EHPH and the results reflect the presence or degree of EV, thus elastography of spleen is useful in monitoring portal hypertension before and after shunt surgeries.

Cat scratch disease is known to be a generally benign, self-resolving illness associated with non-specific symptoms, including lymphadenopathy, fever, fatigue, anorexia, and headaches. However, it can also cause disseminated disease with a wide range of manifestations, including liver and spleen microabscesses, osteomyelitis, encephalitis, and uveitis. Eighteen pediatric cases of disseminated cat scratch disease at a single center in Hawai'i are described. This case series emphasizes the importance of disease recognition and use of appropriate diagnostic tools and disease management. The disease burden of pediatric patients with disseminated cat scratch disease in the state of Hawai'i has a high incidence and should be considered in pediatric patients with prolonged febrile illnesses., Competing Interests: None of the authors identify any conflict of interest., (©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Newcastle disease virus (NDV) replication depends on the translation machinery of the host cell; therefore, the eukaryotic translation initiation factor 2 (eIF2) gene family is a likely candidate for control of viral replication. We hypothesized that differential expression of host genes related to translation and innate immune response could contribute to differential resistance to NDV in inbred Fayoumi and Leghorn lines. The expression of twenty-one genes related to the interferon signaling pathway and the eIF2 family was evaluated at two- and six-days post infection (dpi) in the spleen from both lines, either challenged by NDV or nonchallenged. Higher expression of OASL in NDV challenged versus nonchallenged spleen was observed in Leghorns at 2 dpi. Lower expression of EIF2B5 was found in NDV challenged than nonchallenged Fayoumis and Leghorns at 2 dpi. At 2 dpi, NDV challenged Fayoumis had lower expression of EIF2B5 and EIF2S3 than NDV challenged Leghorns. At 6 dpi, NDV challenged Fayoumis had lower expression of EIF2S3 and EIF2B4 than NDV challenged Leghorns. The genetic line differences in expression of eIF2-related genes may contribute to their differential resistance to NDV and also to understanding the interaction between protein synthesis shut-off and virus control in chickens.

Purpose:  To assess liver stiffness (LS) and spleen stiffness (SS) values measured by virtual touch quantification (VTQ) technique in the monitoring of portal pressure and their usefulness for the prediction of the exacerbation of esophageal varices (EV) in patients with gastric varices undergoing balloon-occluded retrograde transvenous obliteration (B-RTO)., Materials and Methods:  The LS, SS, and hepatic venous pressure gradient (HVPG) were measured in 20 patients both before and after B-RTO. The change in each parameter between the two groups (EV exacerbation and non-exacerbation groups) was compared by analysis of variance. The efficacy of the parameters for the prediction of the exacerbation of EV was analyzed using a receiver operating characteristic (ROC) curve analysis., Results:  9 patients (40.9 %) exhibited an exacerbation of EV within 24 months after B-RTO. Significant changes were observed in the HVPG and SS after B-RTO between the two groups (EV exacerbation group vs. non-exacerbation group: HVPG before 12.7 ± 4.4 mmHg vs. 11.0 ± 4.4 mmHg; HVPG after 19.6 ± 6.0 mmHg vs. 13.6 ± 3.1 mmHg P = 0.003; SS before 3.40 ± 0.50 m/s vs. 3.20 ± 0.51 m/s; SS after 3.74 ± 0.53 m/s vs. 3.34 ± 0.43 m/s P = 0.016). However, no significant changes in LS were observed between the two groups. The area under the ROC curves of elevation in HVPG and SS for the prediction of the exacerbation of EV after B-RTO were 0.833 and 0.818, respectively., Conclusion:  Elevation of the HVPG and SS measured by VTQ after B-RTO was useful for the prediction of the exacerbation of EV., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria.

The academic thought of professor CHEN Ri - xin on "no allergy without any deficiency" was explored. Theory and the clinical application were elaborated on allergic diseases treated with heat-sensitive moxibustion. It is believed that the critical pathogenesis of allergic diseases is deficiency, particularly the deficiency of the lung, the spleen and the kidney. The invasion of exogenous factors or the disturbance of the retained pathogens in the body may induce allergy. Regarding the therapeutic method, the warming method is applicable for the deficiency and the heat-sensitization counteracts allergy. The sensitized points are detected in accordance with the two-step location method and they are stimulated with the suspended moxibustion. The feeling of heat-sensitive moxibustion is a sign of activation of endogenous regulatory function in the human body. It is a kind of external therapy for the internal disorders, directly acting on the pathogenesis, strengthening the antipathogenic qi and removing the allergic factors. This therapy is a new endogenous anti-allergic approach.

Objective: To investigate the fecal microbiota changes in patients with spleen (Pi)-deficiency (SPD), a common Chinese medicine syndrome with digestive and absorptive disturbances and to provide insight into the relationship between Chinese medicine syndrome and gut dysbiosis., Methods: Fecal microbiotas from the stool samples of 53 SPD patients and 35 healthy subjects were analyzed via 16S rRNA gene polymerase chain reaction (PCR)-denaturation gradient gel electrophoresis (DGGE). SPD-related marker genes from 20 SPD patients and 20 healthy subjects were identified through gene sequencing, while some genes were quantified using quantitative PCR (qPCR). Discriminant analysis was conducted using SPSS software, and the canonical discriminant function formula for Pi-deficiency was established., Results: Alterations in microbiota diversity and composition between the SPD and healthy groups were demonstrated via 16S rRNA gene PCR-DGGE combined with multivariate statistical analysis. Fecal microbiota changes were also observed among different SPD-subtype patients. Eight SPD-related markers were found, and putative species corresponding to these markers were identified through gene sequencing, which may have potential associations with the common digestive dysfunctions in SPD patients. qPCR methods were established for two of these markers, which were significantly altered in the SPD patients. The canonical discriminant function formula was calculated for SPD, and the validity rates of these markers were over 85%., Conclusion: Fecal microbiotas are altered in patients with SPD, which may provide insight for further studies on clinically diagnosing and treating SPD. The results may also provide data to gain a better understanding of Traditional Chinese Medicine syndrome and gut dysbiosis.

Background & Aims: Several non-invasive tests (NITs) have been developed to diagnose oesophageal varices (EV), including the recent Baveno VI criteria to rule out high-risk varices (HRV). Spleen stiffness measurement (SSM) with the standard FibroScan® (SSM@50Hz) has been evaluated. However, the EV grading could be underestimated because of a ceiling threshold (75 kPa) of the SSM@50Hz. The aims were to evaluate SSM by a novel spleen-dedicated FibroScan® (SSM@100Hz) for EV diagnosis compared with SSM@50Hz, other validated NITs and Baveno VI criteria., Methods: This prospective multicentre study consecutively enrolled patients with chronic liver disease; blood data, endoscopy, liver stiffness measurement (LSM), SSM@50Hz and SSM@100Hz were collected., Results: Two hundred and sixty patients met inclusion criteria. SSM@100Hz success rate was significantly higher than that of SSM@50Hz (92.5% vs 76.0%, P < .001). SSM@100Hz accuracy for the presence of EV (AUC = 0.728) and HRV (AUC = 0.756) was higher than in other NITs. SSM@100Hz AUC for large EV (0.782) was higher than SSM@50Hz (0.720, P = .027). AUC for HRV with SSM@100Hz (0.780) was higher than with LSM (0.615, P < .001). The spared endoscopy rate of Baveno VI criteria (8.1%) was significantly increased by the combination to SSM@50Hz (26.5%) or SSM@100Hz (38.9%, P < .001 vs others). The missed HRV rate was, respectively, 0% and 4.7% for combinations., Conclusions: SSM@100Hz is a new performant non-invasive marker for EV and HRV providing a higher accuracy than SSM@50Hz and other NITs. The combination of Baveno VI criteria and SSM@100Hz significantly increased the spared endoscopy rate compared to Baveno VI criteria alone or combined with SSM@50Hz. Clinical trial number: NCT02180113., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To evaluate the clinical efficacy and safety of Shugan Jieyu Capsules,Jieyu Pills and Xiaoyao Pills in the treatment of liver-stagnation and spleen-deficiency depression by the network Meta-analysis( NMA),so as to provide evidence-based clinical practice. Chinese databases,including CNKI,VIP,Wan Fang Data,CBM as well as English databases including the Cochrane Library,PubMed,EMbase and Web of Science were retrieved from inception to October 30,2018,to collect randomized controlled trials( RCTs) about clinical study of the three kinds of Chinese patent medicines. The quality and bias risk of the included studies were assessed by 5. 1 standard in Cochrane Handbook,ADDIS software was applied in the statistical analysis,and the result were compared by NMA. A total of 37 studies involving 3 105 patients were included. The results of NMA showed that the adjuvant therapy with the three kinds of traditional Chinese patent medicines could improve the clinical efficacy. Jieyu Pills had the most significant effect( OR = 4. 59,95%CI[1. 94,12. 71],P&lt;0. 05). In HAMD,Shugan Jieyu Capsules( MD = 3. 22,95%CI[2. 07,4. 39],P&lt; 0. 05) and Xiaoyao Pills( MD= 2. 23,95%CI[0. 41,4. 03],P&lt;0. 05) can effectively reduce the depression scale indicators. In the incidence of adverse reactions,the three kinds of Chinese patent medicines can reduce the incidence of adverse reactions. The three kinds of Chinese patent medicines can be combined with auxiliary Western medicine to treat liver-stagnation and spleen-deficiency depression,with complementary advantages in action mechanisms. In the clinical efficacy and safety,the Chinese patent medicines had good clinical manifestations. Although this study showed that Jieyu Pills may be the referred medicine for depression,this conclusion is still immature and needs to be further verified by high-quality RCTs studies,and the application shall be selective based on specific characteristics in clinic.

Phenotypical study was carried out in rats with pendulum movements. The animals exhibited a high level of abortive seizures in response to audiogenic stimuli and longer postictal catalepsy in comparison with those in Wistar population. Seizure severity positively correlated with the duration of poststimulus catalepsy (r=0.90). High aggressiveness towards humans, the absence of BP elevation in stress, lower body weights, and lower weights of the kidneys and spleen in PM rats are considered concomitant traits. Correlations were detected between startle-1 and BP in rats with pendulum movements (r=0.70) and between startle-10 and BP in narcotized Wistar rats (r=-0.0.71). The newly described signs in rats with pendulum movements did not contradict the signs of the focal seizure model with typical automatisms in humans.

It is documented that tlx1, an orphan homeobox gene, plays critical roles in the regulation of early spleen developmental in mammalian species. However, there is no direct evidence supporting the functions of tlx1 in non-mammalian species, especially in fish. In this study, we demonstrated that tlx1 is expressed in the splenic primordia as early as 52 hours post-fertilization (hpf) in zebrafish. A tlx1 -/- homozygous mutant line was generated via CRISPR/Cas9 to elucidate the roles of tlx1 in spleen development in zebrafish. In the tlx1 -/- background, tlx1 -/- cells persisted in the splenic primordia until 52 hpf but were no longer detectable after 53 hpf, suggesting perturbation of early spleen development. The zebrafish also exhibited congenital asplenia caused by the tlx1 mutation. Asplenic zebrafish can survive and breed normally under standard laboratory conditions, but the survival rate of animals infected with Aeromonas hydrophila was significantly lower than that of wild-type (WT) zebrafish. In asplenic zebrafish, the mononuclear phagocyte system was partially impaired, as demonstrated by retarded b7r expression and reduced ccr2 expression after injection with an inactivated A. hydrophila vaccine. Furthermore, the expression of MHCII/IgM was significantly reduced in the congenitally asplenic fish compared with that of the WT zebrafish. Taken together, our data suggest that tlx1 is a crucial regulator of spleen development in fish, as it is in mammals. We have also provided a new perspective for studying the role of the spleen during pathogen challenge in fish., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To assess the utility of spleen stiffness as a diagnostic tool in individuals with human immunodeficiency virus (HIV) and non-cirrhotic portal hypertension (NCPH).The Philips EPIQ7, a new point shearwave elastography (pSWE) technique, was used to assess liver and spleen stiffness in 3 patient groups. Group 1: HIV and NCPH (n = 11); Group 2: HIV with past didanosine (ddI) exposure without known liver disease or NCPH (n = 5); Group 3: HIV without known liver disease or ddI exposure (n = 9).Groups were matched for age, HIV chronicity, and antiretroviral treatment (including cumulative ddI exposure in Groups 1 and 2). Differences in liver and spleen stiffness (in kPa) between groups were analyzed using the Mann-Whiney U test.Liver and spleen stiffness were both significantly higher in NCPH versus ddI-exposed (P = .019 and P = .006) and ddI-unexposed controls (P = .038 and P < .001). Spleen stiffness was more effective than liver stiffness at predicting NCPH, area under receiver operating characteristic (AUROC) 0.812 versus 0.948. Combining the 2 variables improved the diagnostic performance, AUROC 0.961. The optimal cut-off for predicting NCPH using splenic stiffness was 25.4 kPa, with sensitivity 91%, specificity 93%, positive predictive value (PPV) 91%, negative predictive value (NPV) 93%, positive likelihood ratio 12.73, negative likelihood ratio 0.10. Spleen and liver stiffness scores were strongly correlated (P = .0004, 95% confidence interval [CI] 18, 59).Elevated spleen stiffness is observed in HIV with NCPH and can be quantified easily using pSWE with high diagnostic accuracy. Novel strategies such as pSWE for longitudinal monitoring of patients with HIV and NCPH should be considered.

Objectives: The aim of the study was to determine the accuracy of noninvasive parameters, such as liver (LS) and spleen stiffness (SS) to detect esophageal varices (EV) in children with biliary atresia (BA)., Methods: Children with BA between 2000 and 2015 were recruited. All underwent esophagogastroduodenoscopy and transient elastography. Demographic data, laboratory investigations, alanine transferase-to-platelet ratio index (APRI), and Varices Prediction Rule (VPR) score were collected., Results: A total of 51 children (mean age 10.63 years, standard deviation (SD) = 6.08 years; 53% boys) were enrolled. There were differences in onset and outcome of portoenterostomy, spleen palpablility, platelet count, albumin, LS, SS, and VPR between the varice and varice-free groups (P < 0.05). In the varice group, the median LS was 18.12 (interquartile ratio, IQR 13.15-19.12) and the median SS was 46.85 (IQR 25.95-54.55) kPa. In the varice-free group, the median LS was 7.85 (IQR 5.88-16.75) and the median SS was 16.54 (IQR 11.75-21.75) kPa. Both LS and SS were higher in the varice than the varice-free group (P < 0001). The area under the receiver operating characteristic curve of LS, SS, spleen palpability, platelet count, APRI, and VPR were 0.734, 0.870, 0.817, 0.810, 0.751, and 0.794, respectively. Using a cut-off value of 12.5 kPa for LS, the sensitivity and specificity were 80 and 70%, respectively. Using a cut-off value of 28.9 kPa for SS, the sensitivity and specificity were 75 and 87%, respectively. Combination of LS and SS to diagnose varices increased the specificity to 93%., Conclusions: SS as a single marker had the best diagnostic value to predict esophageal varices in children with BA. The combination of SS and LS furthermore, increased the diagnostic yield.

Toxoplasma gondii infection induces parasite infiltration and apoptosis in the spleen. However, dose-dependent parasite infiltration, apoptosis, body weight alternations and survival in mice remain largely unknown. In this study, mice were intraperitoneally infected with 10, 30 or 100 tachyzoites of T. gondii, respectively. Parasite infiltration and apoptosis in the spleen were analyzed on days 3, 7, and 9 post-infection by immunohistochemistry and flow cytometry. Significantly higher levels of T. gondii infiltration and apoptosis in the spleen were found in 30 and 100 tachyzoites infected mice compared to 10 tachyzoites infected mice on days 7 and 9 post-infection. Although 30 and 100 tachyzoites infected mice showed significant body weight loss compared to 10 tachyzoites infected mice, all of the 100, 30, and 10 tachyzoites infected mice died by days 12, 15, and 17, each respectively. Interestingly, T. gondii infiltration in 10 tachyzoites infected mice were limited to capsule area of the spleen on day 9 post-infection. Several areas of parasite infiltrations were found in the 30 tachyzoites infected mice, where noticeable levels of splenic capsule de-adhesion occurred. These results indicated that parasite infiltration and apoptosis in the spleen, as well as body weight loss (survival) are closely correlated with infection dosage. The level of T. gondii infiltration and apoptosis in the spleen and splenic de-adhesion were dependent on the parasite dose.

Background and Aim: To evaluate if spleen stiffness measurement (SSM) can rule out the presence of high-risk varices in patients with cirrhosis, avoiding an upper gastrointestinal endoscopy (UGE)., Methods: We enrolled 71 cirrhotic patients irrespective of liver disease's etiology. 2D shear wave elastography (SWE) of spleen and UGE was performed. High-risk varices (HRV) were defined as esophageal varices ≥ 5 mm and/or red spots and any gastric varices., Results: Esophageal varices were documented in 37 (52.1%) and HRV in 25 (35.2%) patients. SSM was not technically feasible in 7/71 patients (9.8%). From the remaining 64 patients, when those with cholestatic liver disease were excluded (n = 17), SSM < 35.8 kPa was found to exclude well the existence of HRV offering an AUROC of 0.854 (p < 0.001), sensitivity 88.9%, negative predictive value (NPV) 91.3%, specificity 72.4%, and positive predictive value (PPV) 66.7%. Only 2/47 patients (4.3%) were misclassified, and 23 (48.9%) could avoid endoscopy. In the total cohort of 64 patients, SSM < 33.7 kPa was found to exclude well the presence of HRV offering AUROC 0.792 (p < 0.001), sensitivity 91.7%, specificity 60%, NPV 92.3%, and PPV 57.9%. The misclassification rate was 3.1% (2/64), while 26/64 (40.6%) could avoid endoscopy., Conclusions: 2D-SWE of spleen is a reliable method for ruling out the presence of HRV in cirrhotic patients. If larger studies confirm our results, a large number of endoscopies could be avoided.

Background and Purpose- Stroke-induced acute severe body weight (BW) loss is associated with a high rate of mortality during a critical poststroke period. Several interventions to reduce weight loss, however, have not been successful. Currently, the biological significance of this extraordinary catabolic process is not well understood. Spleen-derived monocytes/macrophages (MMs) are the major immune cells recruited to the injured brain. The trafficking of MMs has been shown to be important for tissue repair and recovery. The purpose of the study is to investigate whether the BW reduction is essential for MM-mediated immune response for mice to survive and whether a corticosterone-mediated catabolic event underlies the processes. Methods- C57BL/6 male mice (12-week-old) were subjected to transient middle cerebral artery occlusion. BW, total MMs, and their Ly-6C high and Ly-6C low subsets were determined in the spleen, blood, and the brain in poststroke mice. Poststroke survival rate and MM subsets were determined in mice with adrenalectomy, sham-adrenalectomy, and adrenalectomy mice supplemented with corticosterone. Results- Stroke reduced BW with a maximum reduction at day 3 poststroke (17.2±5.2%). The reduction at day 3 was positively linked to injury severity and selective depletion of MMs, but no other types of immune cells, in the spleen. Notably, the splenic MM depletion was significantly greater in mice with severe BW reduction (≥18% at day 3). In the blood, stroke depleted circulating MMs to a similar degree in animals with moderate and severe BW loss. Ly-6C+ monocyte infiltration in the poststroke brain was greater in mice with severe BW loss. Blocking the catabolic process by adrenalectomy significantly increased poststroke mortality, but the mortality was partially rescued by corticosterone supplement in adrenalectomy mice. Conclusions- Stroke-induced BW loss facilitates MM-mediated immune response, and the adrenal corticosterone-mediated catabolic process is necessary for poststroke survival. Visual Overview- An online visual overview is available for this article.

We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 μg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

Many functional diseases are related to dysautonomia, and heart rate variability has been used to assess dysautonomia. However, heart rate variability has not been studied in Spleen-Qi deficiency syndrome (SQDS). Healthy volunteers (n = 37) and patients with SQDS (n = 67), recruited from the Clinic of the State University of Ecatepec Valley were included in the study. Outcome measures were average heart rate, standard deviation of the normal-to-normal heartbeat intervals, low frequency (LF), high frequency (HF) power, and the LF/HF ratio. Also, intestinal peristalsis, gastrointestinal symptoms (GSs), fatigue, and level of attention were measured. Standard deviation of the normal-to-normal heartbeat intervals (17 ± 2.3%) and HF (14 ± 3.1%) were lower in SQDS patients (17 ± 1.3%) than in healthy volunteers. SQDS patients had higher heart rate, LF power, LF/HF ratio, and fatigue scores (9.6 ± 1.12%, 16 ± 2.1%, 22 ± 3.8%, and 21 ± 4.1%). The fatigue correlated positively with the LF/HF ratio and negatively with HF power. The SQDS group had lower concentration performance (16.2 ± 1.9%) in the d2 test. The intestinal peristalsis showed a reduction (15 ± 1.3%) as compared with control. GS score and peristalsis correlated negatively with HF. Our results suggest that the pathology of SDQS could be associated with a low vagal tone which causes a decrease in peristalsis, increased fatigue, reduced attention, and appearance of GSs., (Copyright © 2019. Published by Elsevier B.V.)

The autonomic nervous system innervates all lymphoid tissues including the spleen therefore providing a link between the central nervous system and the immune system. The only known mechanism of neural inhibition of inflammation in the spleen relies on the production of norepinephrine by splenic catecholaminergic fibers which binds to β2-adrenergic receptors (β 2-ARs) of CD4 + T cells. These CD4 + T cells trigger the release of acetylcholine that inhibits the secretion of inflammatory cytokines by macrophages through α7 nicotinic acetylcholine receptor (α7nAchRs) signaling. While the vagal anti-inflammatory pathway has been extensively studied in rodents, it remains to be determined whether it coexists with other neural pathways. Here, we have found that three nerve branches project to the spleen in mice. While two of these nerves are associated with an artery and contain catecholaminergic fibers, the third is located at the apex of the spleen and contain both catecholaminergic and cholinergic fibers. We found that electrical stimulation of the apical nerve, but not the arterial nerves, inhibited inflammation independently of lymphocytes. In striking contrast to the anti-inflammatory pathway mechanism described so far, we also found that the inhibition of inflammation by apical nerve electrical stimulation relied on signaling by both β 2-ARs and α7nAchRs in myeloid cells, with these two signaling pathways acting in parallel. Most importantly, apical splenic nerve electrical stimulation mitigated clinical symptoms in a mouse model of rheumatoid arthritis further providing the proof-of-concept that such an approach could be beneficial in patients with Immune-mediated inflammatory diseases., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is associated with an increased susceptibility to infections, such as pneumonia, which is the leading cause of death in these patients. This phenomenon is referred to as SCI immune deficiency syndrome (SCI-IDS), and has been shown to be more prevalent after high-level transection in preclinical SCI models. Despite the high prevalence of contusion SCIs, the effects of this etiology have not been studied in the context of SCI-IDS. Compared to transection SCIs, which involve a complete loss of supraspinal input and lead to the disinhibition of spinally-generated activity, contusion SCIs may cause significant local deafferentation, but only a partial disruption of sympathetic tone below the level of injury. In this work, we investigate the effects of thoracic (T6-7) and cervical (C6-7) moderate-severe contusion SCIs on the spleen by characterizing splenic norepinephrine (NE) and cortisol (CORT), caspase-3, and multiple inflammation markers at 3- and 7-days post-SCI. In contrary to the literature, we observe an increase in splenic NE and CORT that correspond to an increase in caspase-3 after thoracic SCI relative to cervical SCI. Further, we found differences in expression of leptin, eotaxin, IP-10, and IL-18 that implicate alterations in splenocyte recruitment and function. These results suggest that incomplete SCI drastically alters the level-dependence of SCI-IDS.

Objectives: To evaluate whether abdominal ultrasound (US) with a gallbladder (GB) contractility study or motor function test can be used as a diagnostic tool in patients with dengue and warning signs in acute and recovery phases., Methods: Fifty-one individuals in the acute phase of dengue presenting with warning signs (dengue group) and 49 healthy individuals without a history of dengue or hepatobiliary disease (control group) were studied with abdominal US and a GB contractility study., Results: Statistical differences in US measurements of the liver (right lobe, P = .012; left lobe, P = .001) and spleen (P = .008) dimensions, GB wall thickness (P < .001), and the GB emptying fraction (P < .001) were observed in dengue during the acute phase compared with the control group. After 60 days, abdominal US of the dengue group showed a statistical difference in liver (right lobe, P < .001; left lobe, P = .078) and spleen (P < .001) dimensions, GB wall thickness, and the GB emptying fraction (P < .001) compared with the results obtained during the acute phase. Furthermore, a statistical difference in the spleen volume and GB emptying fraction (P < .001) was observed when comparing dengue after clinical recovery and the control group. Abdominal pain in patients with dengue was positively associated with hepatomegaly (P = .031), splenomegaly (P = .008), increased GB wall thickness (P = .016), and a reduced GB emptying fraction (P = .038) during the acute phase and with splenomegaly (P = .001) and a reduced GB emptying fraction (P = .003) after clinical recovery., Conclusions: Abdominal US with a GB motor function test can be used as a diagnostic tool in patients with dengue during acute and recovery phases., (© 2018 by the American Institute of Ultrasound in Medicine.)