OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

AIM: To analyze the factors influencing total corneal surgically induced astigmatism(SIA)following implantable collamer lens(ICL)implantation.METHODS:This prospective study enrolled 162 patients(162 eyes)who underwent ICL implantation at our hospital between July 2023 and January 2024. Based on preoperative assessment of anticipated postoperative residual astigmatism, different incisions were selected. Superior incision was selected for patients with expected residual astigmatism with the rule in 75 eyes, and temporal incision was selected for patients with expected residual astigmatism againist the rule in 87 eyes. Parameters including total corneal refractive power, incision length, internal ostium-to-visual axis distance, central corneal thickness, preoperative total corneal astigmatism, and corneal diameter were measured using the Pentacam anterior segment analyzer before and at 3 mo after surgery. Postoperative total corneal SIA was calculated based on the changes in total corneal refractive power. Multiple linear regression analysis was performed to assess the influence of the above parameters on postoperative total corneal SIA.RESULTS:A total of 162 cases(162 eyes)that implanted with ICL were included in the analysis, and 8 cases were lost to follow-up, with a loss rate of 4.9%. Eventually 154 cases(154 eyes)completed the research. The superior incision group comprised 72 cases(72 eyes), including 17 males and 55 females, with a mean age of 25.96±6.17 years, while the temporal incision group comprised 82 cases(82 eyes), including 20 males and 62 females, with a mean age of 27.79±6.47 years. No significant difference in postoperative total corneal SIA was observed between the two groups [0.31(0.21, 0.49)D vs. 0.27(0.13, 0.485)D, P=0.159]. Multiple linear regression analysis revealed that internal ostium-to-visual axis distance and preoperative total corneal astigmatism significantly influenced postoperative total corneal SIA in the superior incision group(P=0.001). The regression equation was: postoperative total corneal SIA=0.71-0.381×internal ostium-to-visual axis distance+0.16×preoperative total corneal astigmatism. No significant influencing factors for postoperative total corneal SIA were identified in the temporal incision group.CONCLUSION: During ICL implantation, the magnitude of total corneal SIA is comparable between superior and temporal incisions. For patients receiving a superior incision, the internal ostium-to-visual axis distance and preoperative total corneal astigmatism value can be used to quantitatively predict postoperative total corneal SIA to a certain extent, thereby aiding in the optimization of postoperative visual quality.

AIM: To evaluate the postoperative clinical efficacy of non-diffractive extended depth of focus intraocular lens(EDOF IOL)in patients with highly myopic cataract(HMC).METHODS:A retrospective analysis was conducted on the clinical data of patients diagnosed with HMC at the hospital from January 2022 to December 2024. Patients were divided into an observation group [undergoing femtosecond laser-assisted cataract surgery(FLACS)combined with non-diffractive EDOF IOL implantation] and a control group(undergoing FLACS combined with aspheric monofocal IOL implantation)according to the type of implanted IOL. Postoperative visual acuity(LogMAR), visual quality, and patient satisfaction were compared between the two groups.RESULTS: A total of 33 patients(47 eyes)were finally included in this study, including 10 patients(17 eyes)in the observation group and 23 patients(30 eyes)in the control group. The observation group had a median age of 59.0(52.8, 63.8)y, with 8 males(13 eyes)and 2 females(4 eyes). The control group had a median age of 56.0(53.5, 60.0)y, with 13 males(17 eyes)and 10 females(13 eyes). At 3 mo postoperatively, the best-corrected distance visual acuity(BCDVA)was 0.10(0.08, 0.12)in the observation group and 0.20(0.10, 0.40)in the control group(P=0.586). However, the best-corrected intermediate visual acuity(BCIVA)[0.10(0.10, 0.10)vs 0.50(0.40, 0.90), P=0.032] and best-corrected near visual acuity(BCNVA)[0.20(0.18, 0.20)vs 0.60(0.45, 1.45), P=0.044] in the observation group were significantly better than those in the control group. The defocus curve showed that the uncorrected visual acuity(UCVA)in the observation group was relatively stable within the range of -2.00 to +1.00 D, which was superior to that in the control group. Postoperative questionnaires showed that the spectacle independence rate(76%)and overall satisfaction(88%)in the observation group were significantly higher than those in the control group(10% and 60%, respectively).CONCLUSION: Non-diffractive EDOF IOL significantly improves intermediate and near visual acuity, reduces spectacle dependence, and maintains distance visual acuity by extending the depth of focus, providing better postoperative visual quality and life satisfaction for HMC patients.

ObjectiveTo investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions， critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years， which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated， in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation， anti-infection， vasoactive drugs， intensive insulin therapy， and organ support， which show limited effects of reducing the mortality. Therefore， finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years， studies have shown that traditional Chinese medicine （TCM） can regulate the PI3K/Akt pathway via multiple pathways， multiple effects， and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis， which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover， studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation， reduce oxidative stress， and control apoptosis in the prevention and treatment of sepsis. Despite the research progress， a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years， this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis， aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

OBJECTIVE: To explore the clinical manifestations and genetic etiology of a child with Progressive familial intrahepatic cholestasis (PFIC2). METHODS: From April 2024 to June 2024, a child with jaundice, hepatomegaly and abnormal liver function who was repeatedly admitted to the First Department of Pediatrics of Qinzhou Maternal and Child Health Care Hospital was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and her parents. Genomic DNA was extracted for trio-whole exome sequencing, the candidate variant was verified by Sanger sequencing and bioinformatic analysis using REVEL, BLAST/BLAT, Swiss-Model and Swiss-Pdb Viewer software. This study was approved by the Medical Ethics Committee of the Qinzhou Maternal and Child Health Care Hospital (Ethics No.: L20240116). RESULTS: The child was a 1.5-month-old female. Her main clinical manifestations included jaundice, hepatomegaly, brownish urine and earth-like stool. Laboratory examination showed increased levels of bilirubin, mainly direct bilirubin, increased aminotransferase, especially glutamic oxalacetic aminotransferase, accompanied by increased bile acid. Genetic testing revealed that the she has harbored a homozygous c.3410T>G (p.V1137G) variant of the ABCB11 gene, for which both of her parents were heterozygous carriers. The variant was unreported previously, and was predicted to be pathogenic based on REVEL. Prediction with BLAST/BLAT software showed that the amino acids were highly conserved among different species. Swiss-Pdb Viewer software predicted that the variant has resulted in changes in hydrogen bonds between amino acids. According to the guidelines from the American Collage for Medical Genetics and Genomics (ACMG), the variant was determined to be likely pathogenic (PM1+PM2_Supporting+PM3_Supporting+PP3_Moderate). CONCLUSION The homozygous variant of the ABCB11 gene may be the genetic cause of this child. Genetic testing is helpful for confirming the diagnosis and enrich the mutational spectrum of the ABCB11 gene.
Humans ; Cholestasis, Intrahepatic/genetics* ; Female ; Infant ; ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics* ; Homozygote ; Mutation

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a common digestive system disease with high prevalence and recurrence rates for years， high treatment costs， and serious impacts on patients' quality of life and economic burden. Therefore， it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex， in which the gut-brain axis is a key factor. The gut-brain axis， a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system， regulates gastrointestinal motility， secretion， and immune responses， playing a key role in the occurrence and development of IBS-D. Up to now， antidiarrheal agents， probiotics， and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease， the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine （TCM） has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However， there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years， this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment， providing new ideas for the treatment of IBS-D.