ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance of non-small cell lung cancer （NSCLC） cells （A549/DDP） by regulating endoplasmic reticulum stress （ERS） via the nuclear factor E₂-related factor 2 （Nrf2）/reactive oxygen species （ROS）/double-stranded RNA-activated protein kinase R （PKR）-like endoplasmic reticulum kinase （PERK）/CCAAT enhancer-binding protein homologous protein （CHOP） signaling pathway. MethodsSprague Dawley （SD） rats were used to prepare blank serum and Buzhong Yiqitang-containing serum samples， and A549/DDP cells were sub-cultured and randomly allocated into 9 groups： Blank （10% blank rat serum medium）， model （10% blank rat serum medium+20 mg·L^-1 cisplatin）， traditional Chinese medicine（TCM） （10% Buzhong Yiqitang-containing rat serum medium+20 mg·L^-1 cisplatin）， TBHQ （10% blank rat serum medium+5 μmol·L^-1 TBHQ+20 mg·L^-1 cisplatin）， TBHQ+TCM （10% Buzhong Yiqitang-containing rat serum medium+5 μmol·L^-1 TBHQ+20 mg·L^-1 cisplatin）， NAC （10% blank rat serum medium+600 μmol·L^-1 NAC+20 mg·L^-1 cisplatin）， NAC+TCM （10% Buzhong Yiqitang-containing rat serum medium+600 μmol·L^-1 NAC+20 mg·L^-1 cisplatin）， Salubrinal （10% blank rat serum medium+20 μmol·L^-1 Salubrinal+20 mg·L^-1 cisplatin）， and Salubrinal+TCM （10% Buzhong Yiqitang-containing rat serum medium+20 μmol·L^-1 Salubrinal+20 mg·L^-1 cisplatin）. The median inhibitory concentration （IC₅₀） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method. The ROS level was detected by flow cytometry. The ultrastructure of endoplasmic reticulum （ER） was observed by transmission electron microscopy. Western blot was employed to determine the protein levels of Nrf2， phosphorylated （p）-Nrf2， CHOP， PERK， p-PERK， eukaryotic translation initiation factor 2α （eIF2α）， p-eIF2α， and activated transcription factor 4 （ATF4）. The fluorescence intensity of CHOP and p-PERK was detected by confocal fluorescence localization. ResultsCompared with the model group， the TCM group showed a decrease in IC₅₀ of cisplatin in A549/DDP cells （P<0.01）. TBHQ， NAC， and Salubrinal groups showed increases in IC₅₀ of cisplatin in A549/DDP cells （P<0.01）. TCM combined with TBHQ， NAC， and Salubrinal reduced the IC₅₀ （P<0.01）. Compared with that in the blank group， the ROS level in the model group elevated （P<0.01）. Compared with that in the model group， the ROS level in the TCM group elevated （P<0.01）. The ROS levels in the TBHQ， NAC， and Salubrinal groups were lower than that in the model group （P<0.01）. The combinations of TBHQ， NAC， and Salubrinal with TCM raised the ROS levels of A549/DDP cells （P<0.01）. A flat saclike and neatly arranged ER structure was observed in the blank group， and slight expansion of ER was observed in the model group. Significant expansion of ER was observed in the TCM group. The expansion of ER was not obvious in the TBHQ， NAC， and Salubrinal groups but significant after TBHQ， NAC， and Salubrinal were combined with TCM. CHOP and p-PERK showed higher fluorescence intensity in the model group than in the blank group （P<0.01）， and the fluorescence signal intensity in the TCM group was higher than that in the model group （P<0.01）. The fluorescence intensity in the TBHQ， NAC， and Salubrinal groups was lower than that in the model group （P<0.01）. The fluorescence intensity in the groups of TBHQ， NAC， and Salubrinal combined with TCM was higher than that in corresponding groups without TCM （P<0.01）. Compared with those in the blank group， the expression levels of Nrf2 and p-Nrf2 were up-regulated in the model group （P<0.05）. Compared with the model group， the TCM group showed down-regulated expression levels of Nrf2 and p-Nrf2 （P<0.05）. TBHQ， NAC， and Salubrinal increased the expression levels of Nrf2 and p-Nrf2 （P<0.05）， while their combinations with TCM decreased the expression levels of Nrf2 and p-Nrf2 compared with the corresponding groups without TCM （P<0.01）. There were no significant differences in the expression levels of PERK and eIF2α between groups. The expression levels of CHOP， p-PERK/PERK， p-eIF2α/eIF2α， and ATF4 were up-regulated in the model group compared with those in the blank group （P<0.05）. Compared with the model group， the TCM group showed up-regulated expression levels of CHOP， p-PERK/PERK， p-eIF2α/eIF2α， and ATF4 （P<0.05）， while the TBHQ， NAC， and Salubrinal groups showed down-regulated expression levels （P<0.05）. The groups of TBHQ， NAC， and Salubrinal combined with TCM had higher expression levels than the groups without TCM （P<0.01）. ConclusionBuzhong Yiqitang regulates ERS via the Nrf2/ROS/PERK/CHOP signaling pathway to attenuate cisplatin resistance in NSCLC.

ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer （NSCLC） by inducing ferroptosis via poly（rC）-binding protein 1 （PCBP1）. MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer （NSCLC） cells （A549/DDP） were cultured and randomly grouped as follows： Blank （10% blank serum）， model （10% blank serum+20 mg·L^-1 cisplatin）， Buzhong Yiqitang （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin）， Fe-1 （10% blank serum+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）， and Buzhong Yiqitang+Fe-1 （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）. Firstly， PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang， and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently， the median inhibitory concentration （IC₅₀） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 （GPX4） were determined by Western blot. The lipid reactive oxygen species （ROS） content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde （MDA） assay kit was used to determine the MDA content in each group. ResultsCompared with model group， the IC₅₀ of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group （P<0.05） but increased in the Fe-1 group （P<0.05）. The IC₅₀ of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group （P<0.05）. Compared with the model group， the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis， while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group， the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group， the model group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05） in A549/DDP cells. Compared with model group， the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）， while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 （P<0.05） and reduced content of lipid ROS， ferrous ions， and MDA （P<0.05）. Compared with the Fe-1 group， the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）. ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer by observing the effects of Buzhong Yiqitang on endoplasmic reticulum stress-related molecules in human lung adenocarcinoma cells （A549） and cisplatin-resistant cells in human lung adenocarcinoma cells （A549/DDP） via the nuclear factor E₂-related factor 2（Nrf2）/reactive oxygen species（ROS） pathway. MethodsThe serum containing Buzhong Yiqitang was prepared and A549 cells and A549/DDP cells were cultured. The cells were randomized into groups A （A549 cells+blank serum）， B （A549 cells+20 mg·L^-1 cisplatin+blank serum）， C （A549 cells+20 mg·L^-1 cisplatin+10% Buzhong Yiqitang-containing serum）， D （A549/DDP cells+blank serum）， E （A549/DDP cells+20 mg·L^-1 cisplatin+blank serum）， and F （A549/DDP cells+20 mg·L^-1 cisplatin+10% Buzhong Yiqitang-containing serum）. The cell counting kit-8 （CCK-8） method was used to detect the half maximal inhibitory concentration （IC₅₀） of cisplatin. The protein levels of Nrf2 and p-Nrf2 were determined by Western blotting. The DCFH-DA fluorescent probe was used to measure the content of reactive oxygen species （ROS） in each group. The protein levels of glucose-regulated protein 78 （GRP78）， activated transcription factor 6 （ATF6）， and C/EBP-homologous protein （CHOP） were determined by Western blot. ResultsCompared with group B， group C showed a reduction in IC₅₀ of cisplatin （P<0.05）， which held true in group E compared with group F （P<0.05）. Moreover， the IC₅₀ of cisplatin to A549/DDP cells was higher than that to A549 cells before and after Buzhong Yiqitang intervention （P<0.05）. Compared with group A， group B showed up-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）. Compared with group B， group C showed down-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）. Compared with group D， group E showed up-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）， which， however， were significantly down-regulated in group F （P<0.05）. The ROS content and the protein levels of GRP78， ATF6， and CHOP followed a descending trend of group C > group B > group A in A549 cells and group F > group E > group D in A549/DDP cells （P<0.05）. Moreover， the ROS content and the protein levels of GRP78， ATF6， and CHOP in A549 cells were higher than those in A549/DDP cells before and after Buzhong Yiqitang intervention （P<0.05）. ConclusionBuzhong Yiqitang may regulate endoplasmic reticulum stress via the Nrf2/ROS pathway to attenuate cisplatin resistance in non-small cell lung cancer.

In the process of tumor chemotherapy， the emergence of multi-drug resistance （MDR） has always been a thorny problem， which is a result of the joint action of the host， tumor cells， and the immune microenvironment. Tumor cells can escape the toxicity of chemotherapeutic drugs through multiple pathways， being easy to produce drug resistance. MDR greatly restricts the effect of chemotherapeutic drugs on tumor cells and affects their therapeutic effects. Traditional Chinese medicine （TCM） has the unique advantages of multi-target， multi-pathway and individualized treatment. The TCM treatment of tumors emphasizes regulating Yin and Yang， as well as reinforcing healthy Qi and dispelling pathogen. In recent years， TCM has demonstrated remarkable efficacy in the treatment of tumors and the amelioration of multi-drug resistance. TCM not only can target the phenomenon of MDR but also greatly weakens the side effects of the patients after the chemotherapy， thus improving the survival quality and rate of the patients. Accordingly， many patients adopt TCM as an adjuvant therapy during or after chemotherapy. The binding of TCM to targets can reverse the drug resistance of various tumors， which has become an emerging research highlight. From the regulatory mechanism of TCM on MDR of tumors， this paper introduces the mechanisms by which tumor cells continue to grow， proliferate， and metastasize by adjusting the intracellular drug concentration， altering or utilizing the tumor microenvironment， and affecting the cell death mode to achieve the resistance to chemotherapeutic drugs. In this regard， the active ingredients and compound prescriptions of TCM can increase the sensitivity of chemotherapeutic drugs by down-regulating drug transporters， improving the tumor microenvironment， and modulating the drug resistance pathways associated with apoptosis， autophagy， ferroptosis， or pyroptosis. The aim of this paper is to explore more clinical practical value of TCM in the treatment of tumors and provide exploratory ideas and a theoretical basis for the future research on tumors and MDR.

ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.