OBJECTIVE To investigate ameliorative effects and mechanisms of two probiotics （Bacillus subtilis， Lactobacillus acidophilus） combined with Aurantii Fructus Immaturus （AFI） on functional dyspepsia （FD） in rats. METHODS Rats were randomly divided into blank group， model group， positive control group （domperidone group， 2.7 mg/kg）， AFI group （9 g/kg）， L. acidophilus group （5×107 cfu/kg）， B. subtilis group （5×107 cfu/kg）， L. acidophilus+ AFI group （L. acidophilus 5×107 cfu/kg+ AFI 9 g/kg）， and B. subtilis+AFI group （B. subtilis 5×107 cfu/kg+AFI 9 g/kg）， with 8 rats in each group. Except for the blank group， FD model was established by tail-clamping stimulation+hunger and satiety disorder+swimming exhaustion in other groups. After modeling， each group was given the corresponding drug/probiotic suspensions/physiological saline intragastrically， once a day， for 14 consecutive days. After the last medication， gastric emptying rate and the rate of propulsion of the small intestine in rats were measured； the levels of brain-gut peptide-related indicators [gastrin （GAS）， substance P （SP）， vasoactive intestinal peptide （VIP）， somatostatin （SS） and cholecystokinin （CCK）] in the serum of rats were measured. The pathological morphology of the gastric antrum tissue and duodenal tissue was observed. Cecal contents from the rats were collected for gut microbiota sequencing analysis. The protein expression levels of tyrosine kinase receptor c-Kit and stem cell factor （SCF） in the gastric antrum tissue， as well as Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor κB （NF-κB） in the duodenal tissue of the rats were detected. RESULTS Compared with the blank group， model group showed significantly lower gastric emptying rate， small intestinal propulsion rate， serum levels of GAS and SP， relative abundance of Firmicutes， Ace， Chao and Sobs indexes of the gut microbiota， and protein levels of SCF and c-Kit in gastric antrum （P＜0.05）， while serum levels of VIP， SS and CCK， relative abundance of Bacteroidetes， as well as protein expressions of TLR4， MyD88， and NF-κB， were significantly higher （P＜0.05）. The histological structure JZYC23S53） of the gastric antrum tissue appeared basically normal； however， abnormalities were observed in the duodenal structure， with a significant infiltration of inflammatory cells visible. Compared with the model group， all treatment groups significantly modulated most of the above indexes （P＜0.05）. The histological structure of the gastric antrum tissue was normal. Except for the B. subtilis group and the B. subtilis+AFI group， the pathological states of the duodenum in the remaining rats gradually recovered. Compared with each single drug group， most of above indexes in rats from each combination group showed further improvement （P＜0.05）. CONCLUSIONS The combination of AFI with two probiotics can improve gastrointestinal motility in FD rats， and the effect is superior to that of using the drugs alone. The specific underlying mechanisms may be related to the activation of the SCF/c-Kit signaling pathway and the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Salmonellosis represents a global epidemic, and the emergence of extensively drug-resistant (XDR) Salmonella and its sustained transmission worldwide constitutes a significant public health concern. Flagellum-mediated motility serves as a crucial virulence trait of Salmonella that guides the pathogen toward the epithelial surface, enhancing gut colonization. Artemisia argyit essential oil, a traditional herb extract, demonstrates efficacy in treating inflammation-related symptoms and diseases; however, its effects on flagellum assembly and expression mechanisms in anti-Salmonella activity remain inadequately explored. This study aimed to elucidate the mechanism by which Artemisia argyit essential oil addresses Salmonella infections. Network pharmacological analysis revealed that Traditional Chinese Medicine (TCM) Artemisia argyit exhibited anti-Salmonella infection potential and inhibited flagellum-dependent motility. The application of Artemisia argyit essential oil induced notable motility defects through the downregulation of flagellar and fimbriae expression. Moreover, it significantly reduced Salmonella-infected cell damage by interfering with flagellum-mediated Salmonella colonization. In vivo studies demonstrated that Artemisia argyit essential oil administration effectively alleviated Salmonella infection symptoms by reducing bacterial loads, inhibiting interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) production, and diminishing pathological injury. Gas chromatography-mass spectrometry (GC-MS) analysis identified forty-three compounds in Artemisia argyit essential oil, with their corresponding targets and active ingredients predicted. Investigation of an in vivo model of Salmonella infection using the active ingredient demonstrated that alpha-cedrene ameliorated Salmonella infection. These findings suggest the potential application of Artemisia argyit essential oil in controlling Salmonella, the predominant food-borne pathogen.
Artemisia/chemistry* ; Oils, Volatile/chemistry* ; Animals ; Flagella/drug effects* ; Salmonella Infections/microbiology* ; Humans ; Mice ; Anti-Bacterial Agents/pharmacology* ; Salmonella/pathogenicity*

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective:To gain a deeper understanding of the cognitive differences between lactating women and obstetric nurses regarding their breastfeeding counselling abilities.Methods:This study was a descriptive phenomenology qualitative study. From October 2021 to June 2022, purposive sampling was used to select 11 lactating women who received breastfeeding counselling and 13 obstetric nurses who provided breastfeeding counselling services in Department of Obstetrics at Peking Union Medical College Hospital for semi-structured interviews. Giorgi analysis method was used to extract and analyze data.Results:The cognitive differences between lactating women and obstetric nurses regarding breastfeeding counselling abilities were mainly manifested in four aspects, namely breastfeeding knowledge and skills, counselling practice ability, improving counselling ability, and personality traits.Conclusions:Lactating women and obstetric nurses have cognitive differences in breastfeeding counselling abilities. Obstetric nurses should improve their breastfeeding counselling skills based on the needs of lactating women and provide personalized breastfeeding counselling services.

Objective To investigate the effect and mechanism of osteopontin(OPN)in hepatoma cell migration through galectin-3 binding protein(LGALS3BP).Methods Human hepatoma cell lines SMMC-7721,SMMC-P(stably transfected with empty eukaryotic expression vectors),and SMMC-OPN(stably transfected with the OPN gene)were cultured.mRNA expression levels of OPN and LGALS3BP were measured by RT-qPCR.Western blot assays were used to analyze the relative protein expression of OPN and LGALS3BP and PI3K/AKT pathway.Wound healing assays were performed to explore the cell migration ability.After transfection with LGALS3BP-targeting small interfering RNA(si-LGALS3BP)or negative control small RNA(si-NC)into SMMC-OPN cells,cell migration and relative expression of PI3K/AKT pathway-related proteins were assessed.Results Compared with SMMC-7721 and SMMC-P,the migratory ability of SMMC-OPN cells was significantly reinforced,and expression of LGALS3BP was obviously upregulated at both mRNA and protein levels.Moreover,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins was significantly increased.Wound healing assays showed that the si-LGALS3BP obviously suppressed the migratory ability of SMMC-OPN cells.Furthermore,relative expression of p-PI3K/PI3K and p-AKT/AKT proteins in SMMC-OPN cells was significantly decreased after transfection of si-LGALS3BP.Conclusions OPN activates the PI3K/AKT pathway by upregulating LGALS3BP expression to promote hepatoma cell migration.

Objective:To design a motor impairment rehabilitation monitoring aid for the assessment of motor impairment in patients who do not have or have difficulty walking independently.Methods:An assistive device vehicle was designed, equipped with an accelerometer and a six-dimensional force sensor. The normal walking (NW) group and abnormal walking group were set up, in which the abnormal walking group included moderate abnormal walking (MA) group, moderate abnormal walking with the aid of the assistive vehicle (MA-V) group, severe abnormal walking (SA) group, and severe abnormal walking with the aid of the assistive vehicle (SA-V) group. In the MA-V group, the range of knee movement was adjusted from 0 to 30°, and in the SA group, the knee joint was completely unbending. The gait cycles, peak and mean acceleration values of the right and left legs were evaluated by accelerometers, and changes in the upper limb forces were assessed by six-dimensional force transducers.Results:For the moderate impairment group, the difference in gait cycle between the MA and MA-V groups was not statistically significant ( P>0.05), and the gait cycle in the MA-V group was slightly greater than that in the MA group. For the severe injury group, the gait cycle of the SA-V group was lower than that of the SA group, and the difference was statistically significant ( P<0.01). For all abnormal groups, the mean and peak acceleration of the left leg were greater than that of the right leg, and the difference between the peak acceleration of the left leg and that of the right leg was statistically significant ( P<0.05). In the abnormal walking pattern, the mean (absolute) value of the left hand force was greater than that of the right hand, especially in the Z-axis. The standard deviations of the combined forces on the left side for the NW, MA-V, and SA-V groups were 2.759, 8.297, and 13.118 N, respectively. The SA-V group had the highest dispersion in the force scatter plot, while the NW group had a better concentration. Conclusions:An assistive vehicle equipped with an accelerometer and a six-dimensional force sensor was designed to help physicians in the assessment and rehabilitation of motor disorders.

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller mo-lecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting ther-apeutics for HCC treatment with low toxic side effects.

Ventilators are currently the most commonly used auxiliary mechanical ventilation equipment in clinical practice, and play an important role in the treatment of hypoxemia. Ventilator-associated pneumonia (VAP) is a special type of pulmonary parenchymal inflammation of nosocomial infection in patients with mechanical ventilation, which leads the increase of mortality and affects the prognosis of patients. The non-standard management of ventilator pipeline joints and the aerosol formed by bacterial condensate splashed from ventilator pipeline pollute the air, resulting in cross infection, which are the important reasons for VAP. The existing ventilator pipeline joint cap can achieve the effect of preventing pollution, but the clinical application compliance is not high. Based on the above factors, teachers, students and medical staff of the School of Public Health and Management, Guangxi University of Chinese Medicine and other units have designed a device for preventing pollution and air pollution of the ventilator pipeline joint, and obtained the national utility model patent of China (ZL 2020 2 1361981.X). The device is composed of a model lung, a mask body, a suspension part and a beam mouth part, etc. The use method is simple, and can be applied to the pollution avoidance of invasive ventilator and non-invasive ventilator pipeline joints, to reduce the occurrence of VAP in patients and the occupational exposure of medical staff.