ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative. Isovalerylspiramycin I (ISP I) as a major component of carrimycin applied to upper respiratory infections, was first found to possess anti-fibrotic potential. The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis. According to our results, ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation (BDL) rats and carbon tetrachloride (CCl₄) mice. We proved that nucleotide-binding protein 2 (NUBP2) was the direct target of ISP I. ISP I through targeting NUBP2, increased the amount of vascular non-inflammatory molecule-1 (VNN1) on the cell membrane, which will inhibit oxidative stress and fibrosis. Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic.

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Objective To investigate the safety and efficacy of combined confluence microdissection or balloon dilatation followed by laparoscopic transcystic common bile duct exploration (LTCBDE) in day surgery laparoscopic cholecystectomy. Methods The clinical data of 203 patients with day surgery laparoscopic cholecystectomy combined with LTCBDE from June 2021 to June 2024 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. They were divided into an observation group (59 cases, including 42 cases of confluent microdissection and 17 cases of balloon dilatation) and a conventional group (144 cases) according to the surgical technique used. Baseline characteristics, intraoperative exploration results, operation time, postoperative recovery and complications were compared between the two groups. Results The history of preoperative cholangitis or pancreatitis (P<0.001) was more common in the observation group. And total bilirubin level was significantly higher in the observation group than in the conventional group (P=0.035). The observation group had a longer operative time (P=0.014) and higher hospitalization costs (P=0.001), but there was no difference in intraoperative bleeding and postoperative discharge time. There were no serious postoperative complications in either group. Conclusions Under the premise of strict patient screening, day surgery LTCBDE combined with confluence microdissection or balloon dilatation can effectively solve the problem of difficult choledochoscopic access, with high safety and thoroughness of exploration. Both techniques provide a feasible minimally observation solution for day surgery biliary exploration.

Indocyanine green has been a popular near-infrared fluorescent reagent in recent years, and indocyanine green fluorescence imaging navigation surgery technology has been widely used in hepatobiliary surgery. Many factors affect imaging in various clinical scenarios, which are roughly divided into liver background fluorescence interference and penetrating tissue thickness, including the dose and timing of the drug, liver lesions of the patient, and individualization of the patient. Under the concept of precise surgery, we should individualise the treatment of patients to minimise the influence of unfavourable factors and further improve the safety and efficacy of surgery. Currently, there is no reliable research evidence to guide the use of indocyanine green in terms of influencing factors, and clinical studies are urgently needed to optimise the use of indocyanine green in hepatobiliary surgery.

Objective To use imaging features of pulmonary nodules to predict the risk of lymph node metastasis in patients with cT1-stage non-small cell lung cancer (NSCLC), providing a reference for clinical decision-making. Methods A retrospective analysis was conducted on the imaging features and postoperative pathological results of cT1 NSCLC patients who underwent surgical treatment at Linyi People’s Hospital from July 2019 to July 2022. Patients were grouped and analyzed according to lymph node metastasis status. Results A total of 1 123 patients were included, comprising 471 males and 652 females, with a median age of 59 (52, 66) years. Comparative analysis revealed that sex, age, nodule location, nodule size on imaging, solid component size, consolidation tumor ratio (CTR), average CT value, and tumor proximity to the pleura all influenced lymph node metastasis. A nomogram was constructed, indicating that the probability of lymph node metastasis in cT1 NSCLC was positively correlated with solid component size, CTR, and average CT value of the pulmonary nodule, and negatively correlated with patient age. The area under the receiver operating characteristic curve was 0.929. Conclusion For cT1 NSCLC patients, the probability of lymph node metastasis can be predicted by measuring the solid component size, CTR, and average CT value of the pulmonary nodule, in conjunction with patient age. However, relying solely on pulmonary nodule imaging characteristics is insufficient to determine a specific lymph node dissection strategy.

Objective: To investigate the prevalence of hyperactivity behavior in children aged 3-6 in Yunnan Province, to explore its relationship with neuropsychological development, so as to provide clues for early prevention and intervention of attention deficit hyperactivity disorder (ADHD) in children. Methods: A total of 1 321 children aged 3 to 6 from 10 kindergartens in 5 prefectures (cities) of Yunnan Province were selected by stratified random sampling method from October 2022 to May 2023. Teacher Rating Scale (TRS) was used to investigate childrens hyperactive behavior and coexistent behavior. A qualified evaluator applied the Developmental Scale for Children Aged 0-6 Years to assess the development of 5 ability areas of gross motor movement，fine movement，adaptive ability，language and social behavior. Statistical analysis was performed using Wilcoxon rank sum test and χ2 test. Binary Logistic regression was applied to analyze the score of their hyperactivity behavior and its relationship with other behavior problems and neuropsychological development. Results: The detection rate of hyperactivity behavior was 8.6% in children aged 3 to 6 years, 12.8% in boys and 4.1% in girls (χ2=31.53, P<0.01). The detection rate of hyperactivity in 3yearold children was 13.9%, which was higher than that in 4yearold (9.2%) and 5yearold children (7.0%) (χ2=8.73, P<0.05). The detection rate of inattentionpassivity of rural children (14.6%) was higher than that of urban children (5.9%) (χ2=22.23, P<0.01). Binary Logistic regression analysis showed that the higher the level of adaptive development, the lower the risk of hyperactivity (OR=0.58, 95%CI=0.39-0.86), the higher the risk of hyperactivity (OR=0.57, 95%CI=0.35-0.91), the higher the risk of conduct problems (OR=0.57, 95%CI=0.37-0.87), inattentionpassivity (OR=0.49, 95%CI=0.33-0.74) were also at lower risk (P<0.05). Children with higher levels of fine motor development had a lower risk of inattentionpassivity (OR=0.59, 95%CI=0.37-0.93, P<0.05). Conclusions Hyperactivity in boys and inattentionpassivity in rural children requires more attention. It is necessary to strengthen childrens early adaptive ability and fine motor training to prevent hyperactive behavior and inattention.

Acute Stanford type A aortic dissection has the characteristics of acute onset, severe condition and high mortality. Once making a definite diagnosis, surgical treatment is needed as soon as possible. It is difficult for cardiac surgeons to treat the acute aortic dissection involving the aortic sinus, which is an important risk factor for death. Improving the surgical treatment for the aortic sinus can be a key to improving the prognosis. In this review, we will introduce the modified sandwich technique for acute Stanford type A aortic dissection and the prognosis, and summarize the experiences of different modified sandwich techniques. However, there is still no unified standardized technique in aortic root repair, and there is a lack of large studies with long-term follow-up, so it is necessary to further improve the aortic root repair techniques.