At present, the treatment of sepsis depends largely on non-specific methods, highlighting an urgent need for novel therapeutic strategies. Stem cells have garnered significant attention in the treatment of various diseases due to their unique biological properties. Stem cells enhance sepsis survival through mechanisms such as reducing bacterial burden, modulating inflammation, and ameliorating organ dysfunction. Recent studies have shown that stem cells can increase the survival rate of sepsis patients through multiple pathways such as reducing the bacterial load of the host, regulating inflammatory homeostasis, and improving multi-organ dysfunction. Their derivatives, exosomes, can also alleviate the imbalanced immune response in sepsis patients. Recent advances in stem cell-based therapies for sepsis were summarized in this paper.

ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 （Fas）/cysteine protease-8 （Caspase-8）/cysteine protease-3 （Caspase-3） signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury （CLI）. MethodsAmong 48 Wistar rats，12 rats were randomly selected as the blank group，and the other rats were administered alpha-naphthalene isothiocyanate （ANIT） by gavage to induce a CLI model. The modeling rats were randomly divided into the model group， the ursodeoxycholic acid group（0.1 g·kg^-1） and the Yinchenhao Tang group（9.23 g·kg^-1），with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），gamma-glutamyl transpeptidase （γ-GT），total bilirubin （TBil） and total bile acid （TBA） in serum were detected. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3，B-cell lymphoma-2 （Bcl-2） associated X protein （Bax） and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with those in the blank group，the levels of ALT，AST，ALP，γ-GT，TBA and TBil in serum of the model group were significantly increased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased （P<0.01）. The arrangement of hepatocytes was disordered，and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly increased（P<0.05，P<0.01），while the protein and mRNA expressions of Bcl-2 were significantly decreased （P<0.05，P<0.01）. Compared with those in the model group，the levels of ALP，γ-GT，TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased（P<0.05，P<0.01）. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the mRNA expression of Bcl-2 was significantly increased （P<0.05，）. The levels of ALT，AST，γ-GT，TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased （P<0.05，P<0.01）. The protein expression of Fas and Bax and the mRNA expression of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the protein and mRNA expression of Bcl-2 were significantly increased （P<0.05，P<0.01）. Hepatocyte injury，inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI，and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

ObjectiveTo explore the mechanism by which Yinchenhao Tang intervenes in α-naphthylisothiocyanate （ANIT）-induced cholestatic liver injury by regulating the Takeda G-protein-coupled receptor 5（TGR5）/NOD-like receptor protein 3（NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1） pyroptosis signaling pathway. MethodsForty male Wistar rats were randomly assigned into blank， model， ursodeoxycholic acid， and Yinchenhao Tang groups. Except the blank group， other groups were treated with ANIT dissolved in olive oil for the modeling of cholestatic liver injury. Ursodeoxycholic acid （0.1 g·kg^-1） and Yinchenhao Tang （9.23 g·kg^-1） were administered by gavage. The blank group and the model group were administrated with the same amount of pure water， once a day for 3 days. The blood and liver tissue samples were collected， and the serum levels of liver function indicators were measured by an automatic biochemical analyzer. Hematoxylin-eosin staining was employed to observe the pathological changes of the liver. The levels of interleukin （IL）-1β and IL-18 in the liver tissue were determined by ELISA. The mRNA levels of IL-1β， IL-18， TGR5， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， and GSDMD in the liver tissue were assessed by Real-time PCR. The protein levels of TGR5， NLRP3， ASC， Caspase-1， and GSDMD in the liver tissue were determined by Western blot. ResultsCompared with the blank group， the model group showed elevated levels of alanine amino-transferase （ALT）， aspartate transferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， and total bilirubin （TBil） in the serum （P<0.01）， inflammatory cell infiltration， hepatocyte swelling， and bile duct epithelial cell proliferation in the liver， raised levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA and protein levels of TGR5 （P<0.01）， up-regulated mRNA levels of IL-18 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， and NLRP3 （P<0.05）， and up-regulated protein levels of NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， and GSDMD （P<0.05）. Compared with the model group， the ursodeoxycholic acid group showed declined levels of AST （P<0.01）， TBA （P<0.01）， TBil （P<0.01）， and ALT （P<0.05） in the serum， lowered levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of NLRP3 （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， IL-18 （P<0.05）， and ASC （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.05）， and down-regulated protein levels of NLRP3， ASC， Caspase-1， and GSDMD （P<0.05）. Compared with the model group， the Yinchenhao Tang group showed lowered levels of ALT， AST， ALP， TBA， and TBil in the serum （P<0.01）， declined levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of IL-1β （P<0.01）， NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， and IL-18 （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.01）， and down-regulated protein levels of Caspase-1 and GSDMD （P<0.05）. The liver tissue of the administration groups showed reduced infiltration of inflammatory cells， reduced swelling of hepatocytes， and alleviated proliferation of bile duct epithelial cells. ConclusionYinchenhao Tang can ameliorate ANIT-induced cholestatic liver injury by regulating the hepatocyte pyroptosis mediated by the TGR5/NLRP3/Caspase-1 signaling pathway.

ObjectiveThis study aims to investigate the mechanism of Yinchenhao Tang （YCHT） in regulating macrophage polarization to alleviate cholestatic liver injury，focusing on the TLR4/NF-κB signaling pathway as the entry point. MethodsCholestasis was induced in Wistar rats through a single gavage of 100 mg·kg^-1 α-naphthyl isothiocyanate （ANIT） dissolved in olive oil. The animals were randomly divided into four groups：Model group，YCHT group，ursodeoxycholic acid （UDCA） group （n=10），and a blank group （n=10） that received only 5 mL·kg^-1 olive oil. The YCHT group received 9.23 g·kg^-1·day^-1 of YCHT by gavage，and the UDCA group was treated with 0.1 g·kg^-1·day^-1 of UDCA suspension. Both the normal and model groups were given an equal volume of normal saline，all for three consecutive days. Serum liver function was assessed using an automatic biochemical analyzer. Hematoxylin-eosin （HE） staining was used to observe liver tissue morphology. Levels of tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），transforming growth factor-β （TGF-β），and interleukin-10 （IL-10） were quantified in liver homogenate supernatants via enzyme-linked immunosorbent assay （ELISA）. Western blot analysis measured the relative protein expression of Toll-like receptor 4 （TLR4），nuclear factor-κB （NF-κB），CD206，inducible nitric oxide synthase （iNOS）， CD86，and arginase-1 （Arg-1）. The relative mRNA expression of TLR4/NF-κB，CD206，iNOS，CD86，and Arg-1 in liver tissue was evaluated using real-time quantitative PCR. ResultsCompared with the normal group，the model group exhibited significantly elevated levels of alkaline phosphatase （ALP），total bile acid （TBA），total bilirubin （TBil），aspartate aminotransferase （AST），and alanine aminotransferase （ALT） （P<0.01）. There was a portal area expansion and pronounced inflammatory cell infiltration. The expression of pro-inflammatory markers TNF-α and IL-1β was significantly upregulated （P<0.01），and macrophage markers CD86 and CD206 showed positive expression. Protein and mRNA expressions of iNOS and CD86 were significantly elevated （P<0.01）. The mRNA and protein expressions of the related pathway molecules TLR4 and NF-κB were significantly increased （P<0.01）. Compared with those in the model group， the liver function indicators in the YCHT group showed significant decreases （P<0.05， P<0.01）. The bile duct hyperplasia was significantly alleviated， and the tissue structure became more orderly. The levels of IL-1β and TNF-α were significantly reduced （P<0.01）， while the expression levels of IL-10 and TGF-β significantly increased （P<0.05， P<0.01）. The expression of CD86 significantly decreased （P<0.01）， and the expression of CD206 significantly increased （P<0.01）. The protein and mRNA expressions of iNOS and CD86 significantly decreased （P<0.01）， and those of Arg-1 significantly increased （P<0.01）. The protein and mRNA expressions of CD206 significantly increased （P<0.05， P<0.01）， and the mRNA and protein expressions of related pathway molecules TLR4 and NF-κB significantly decreased （P<0.01）. ConclusionYCHT ameliorates cholestatic liver injury in rats by improving bile metabolism，reducing bile duct dilatation，and mitigating inflammation. These effects are achieved through the inhibition of M1 macrophage activation and the promotion of M2 macrophage polarization，likely via modulation of the TLR4/NF-κB signaling pathway.

Cholestatic liver injury refers to the bile production， secretion， and excretion disorder caused by various reasons. It induces liver injury， metabolic disorders， and dysfunction of the hepatobiliary system， which can further develop into liver fibrosis， cirrhosis， liver failure， and even death. At present， the preferred drug for clinical treatment is ursodeoxycholic acid， which， however， induces adverse reactions and is intolerant in some patients. Yinchenhao Tang is a representative prescription of traditional Chinese medicine for the treatment of jaundice due to Yang jaundice. It has the effects of clearing heat， eliminating dampness， and removing jaundice and has shown good therapeutic effect in long-term clinical application. Modern pharmacological studies have found that this prescription has anti-inflammatory， anti-oxidation， bile acid balance-regulating， hepatocyte apoptosis-inhibiting and other liver-protecting effects. This paper reviews the relevant clinical and animal experimental studies on Yinchenhao Tang in the treatment of cholestatic liver injury in recent years. Yinchenhao Tang can intervene in the progression of cholestatic liver injury by regulating bile acid metabolism and excretion， reducing inflammatory response， inhibiting oxidative stress， alleviating endoplasmic reticulum stress， inhibiting hepatocyte apoptosis， and protecting intestinal mucosal barrier. This paper systematically expounds the molecular mechanisms by which Yinchenhao Tang regulates cholestatic liver injury that are confirmed by current research， aiming to provide reference for the clinical application and in-depth study of Yinchenhao Tang.

Objective:To analyze the research trends and hotspots of bupivacaine liposomes from 1994 to 2023 using bibliometrics.Methods:A comprehensive search was conducted for the literature related to bupivacaine liposomes in the Web of Science Core Collection from 1994 to 2023. The CiteSpace software was used to conduct an in-depth analysis of the included literature data, including publication year, country, institution, author, journal, cited references, keywords, etc.Results:A total of 875 papers related to bupivacaine liposomes were included. The research and development of bupivacaine liposomes were divided into 3 stages: slow development (1994-2011), a sharp rise (2011-2021), and stabilization (2021-2023). The United States was in a leading position in terms of the number of publications, centrality, and author cooperation, and Harvard University had the largest number of publications. de Paula E had the most publications, Bramlett K had the highest number of citations, and Boogaerts J had the highest centrality of publications. Journals such as Anesthesia and Analgesia made significant contributions to this field. The most cited references focused on the infiltration of wounds and the periprosthetic injection of bupivacaine liposomes. The keyword analysis showed that local anesthetics, postoperative pain, etc. were commonly used keywords, and enhanced recovery after surgery was an emerging hotspot. Conclusions:Bupivacaine liposomes show good application prospects in the field of peripheral nerve block due to their unique pharmacological properties and safety characteristics and are expected to prolong the duration of postoperative analgesia. However, there is a difference between the actual effect and the expectation, and more clinical trials are needed to evaluate the curative effect, providing a more solid and reliable theoretical basis and practical guidance for clinical practice.

Stress refers to the non-specific responses of a stimulated body to different stressors and the subsequent maintenance or restoration of internal environmental homeostasis.Adverse stress reactions lead to general balance disruption and may cause digestive,neurological,and endocrine disorders,and decreased immune capacity,which seriously impact host health.As the core compo-nent of intestinal micro-ecology,the intestinal flora can greatly alter its own composition,distribu-tion,function,metabolic product output,and other aspects during stress,which cause disorders and aggravate homeostatic imbalance in internal environments.While the intestinal flora is of great sig-nificance to animal medicine and agricultural production,little is known about stress and its impact on intestinal flora.Therefore,we briefly reviewed the impact of stress on animal intestinal flora in combination with the latest research and provided theoretical insights on intestinal health research.

Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)＞3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.