In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.

Objective:To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF).Methods:In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People′s Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed.Results:Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion:Matched sibling allo-HSCT is a feasible option for the treatment of MF.

ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg^-1）， valsartan capsule group （10.29 mg·kg^-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L^-1 glucose）， high glucose group （35 mmol·L^-1 glucose）， DMSO group （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS group （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.

ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg^-1）， and losartan capsules （10.29 mg·kg^-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L^-1）， high glucose （35 mmol·L^-1）， DMSO （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.

Objective To investigate the effect of diurnal temperature difference on hospitalization volume of patients with cardiovascular and cerebrovascular diseases in Urumqi City. Methods The daily hospitalization data for cardiovascular and cerebrovascular diseases in Urumqi City from 2019-2021, and meteorological and pollutant data for the same period were collected. The relationship between diurnal temperature range and hospitalizations for cardiovascular and cerebrovascular diseases was analyzed using a distribution lag non-linear model (DLNM), controlling for the long-term trends, the day-of-week effects and other factors. Results The greater the diurnal temperature range, the longer the lag time, and the higher the risk of hospitalization for cardiovascular and cerebrovascular diseases. The lag effect increased significantly when the maximum diurnal temperature range reached 21.0°C. The risk effect appeared on the day of exposure and lasted until day 20, with a maximum RR of 1.266 (95% CI: 1.129-1.421) at a lag of 13 days. At very high diurnal temperature range, the risk of hospitalization for cardiovascular and cerebrovascular diseases was higher in the cold season than that in the warm season. Results after stratified analysis by sex and age showed that men and people aged ≥65 years were more susceptible to diurnal temperature range. Conclusion Extremely high diurnal temperature range is a potential trigger for hospitalization for cardiovascular and cerebrovascular diseases in Urumqi. Men and people aged ≥65 years are more vulnerable to the impact of diurnal temperature range. In the cold season, more attention should be paid to protecting vulnerable people from the impact of the extremely high diurnal temperature difference.

Mice ; Animals ; Humans ; Disease Models, Animal

Background: Due to the unavailability of an effective vaccine or antiviral drug against the African swine fever virus (ASFV), rapid diagnosis methods are needed to prevent highly contagious African swine fever. Objectives: The objective of this study was to establish the ladder-shape melting temperature isothermal amplification (LMTIA) assay for the detection of ASFV. Methods: LMTIA primers were designed with the p72 gene of ASFV as the target, and plasmid pUC57 was used to clone the gene. The LMTIA reaction system was optimized with the plasmid as the positive control, and the performance of the LMTIA assay was compared with that of the commercial real-time polymerase chain reaction (PCR) kit in terms of sensitivity and detection rate using 200 serum samples. Results: Our results showed that the LMTIA assay could detect the 10 4 dilution of DNA extracted from the positive reference serum sample, which was the same as that of the commercial real-time PCR kit. The coincidence rate between the two assays was 100%. Conclusions The LMTIA assay had high sensitivity, good detection, and simple operation. Thus, it is suitable for facilitating preliminary and cost-effective surveillance for the prevention and control of ASFV.